[August 18, 2011] SUGAR-MODIFIED DERIVATIVES OF CYTOSTATIC 6-(HET)ARYL-7-DEAZAPURINE NUCLEOSIDES: 2'-C-METHYLRIBONUCLEOSIDES, ARABINONUCLEOSIDES AND 2'-DEOXY-2'-FLUOROARABINONUCLEOSIDES [Collection of Czechoslovak Chemical Communication] Tweet (Collection of Czechoslovak Chemical Communications Via Acquire Media NewsEdge) A series of novel sugar-modified derivatives of cytostatic 6-hetaryl-7-deazapurine ribonucleosides: 2'-C-methylribonucleosides, arabinonucleosides and 2'-deoxy-2'-fluoroarabinonucleosides bearing an alkyl, aryl and hetaryl group in position 6 were prepared by palladium catalyzed cross-coupling reactions of corresponding (protected) 6-chloro-(7-fluoro)- 7-deazapurine nucleosides with (het)arylboronic, hetarylstannanes and trimethylaluminium eventually followed by deprotection. Key intermediate 6-chloro-7-deazapurine 2'-C-methyl- ß-D-ribofuranoside was prepared via a stereoselective nucleobase anion glycosylation with toluoyl-protected 1,2-anhydro-2-C-methylribofuranose. The 1,2-anhydro sugar was synthesized in 3 steps starting from readily available 2-C-methylribonolactone. The 6-chloro- 7-deazapurine arabinofuranoside intermediate was obtained by epimerization from 3',5'- protected 6-chloro-7-deazapurine ribofuranoside via 2'-hydroxyl oxidation followed by reduction. None of the prepared compounds showed any considerable cytostatic or antiviral activity. Keywords: Nucleosides; Cross-coupling; Antitumor agents; Purines; 7-Deazapurines; 7H-Pyrrolo[2,3-d]pyrimidine; Cytostatic agents. Biological activity of purine ribonucleosides bearing aryl or hetaryl groups at position 6 have been a long term topic of our laboratory (Chart 1). The parent 6-(het)arylpurine ribonucleosides 1 possess1 significant cytostatic and anti-HCV activities. However, any of the prepared 2- and 8-substituted derivatives2 or 2'-, 3'- and 5'-deoxyribonucleosides3 were inactive, whereas the corresponding L-ribonucleosides4 showed only moderate anti-HCV effect. Recently, we found5 that 6-hetaryl-7-deazapurine 2 and 6-hetaryl-7-fluoro-7-deazapurine ribonucleosides 3 exert even pronounced cytostatic effect in nanomolar concentrations. However, their cycloSal-phosphate and ProTide prodrugs6 were less active due to efflux from the cells. Since some sugar-modified purine nucleosides (i.e. Fludarabine7 or Clofarabine8) are clinically used cytostatics and 7-deazaadenine 2'-C-methylribonucleoside9 is in clinical trials for treatment of HCV, we decided to prepare and study the biological activity of three types of sugar-modified derivatives of 6-(hetaryl)-7-deazapurine nucleosides: 2'-C-methylribonucleosides (analogues of the anti-HCV drug candidate), arabinosides (analogues of Fludarabine) and 2'-deoxy-2'-fluoroarabinonucleosides (analogue of Clofarabine). The synthesis of 2'-C-methylribonucleosides required the preparation of 6-chloro-7-deazapurine 2'-C-methylriboside key intermediate. The corresponding free nucleoside was synthesized by Merck researchers10 by nucleobase anion glycosylation of 6-chloro-7-deazapurine with 3,5-bis- O-(2,4-dichlorobenzyl)-2-C-methylribofuranosylbromide followed by benzyl deprotection. The authors later found that actual glycosylating agent is anomeric a-epoxide11 formed from halogenose by internal SN2 reaction of bromohydrin unit under basic reaction conditions. The observed clean stereoselective outcome of nucleosidation (only ß anomer formation) was then explained by SN2 ring opening of a-epoxide. The starting 2-C-methylribofuranosylbromide was prepared by lengthy multi-step sequence from D-ribose. For larger scale preparation of 7-deaza-2'-C-methyladenosine (Chart 2), potent inhibitor of HCV RNA replication, the authors later developed a more suitable toluoyl-protected epoxide 4 11 and successfully utilized it in multi-kilogram glycosylation of N-phtalimido-7-deazaadenine. The epoxide 4 is generated from key diol 5 by mesylation rather than via halogenose. Although practical and efficient, Merck synthesis of key diol 5 comprises nine steps starting from diacetone glucose and thus is not just convenient for rapid access to epoxide 4 in laboratory small scale. We envisaged 2-C-methyl-D-ribonolactone 6 (Scheme 1) as attractive starting material for epoxide 4, because it is a product of calcium hydroxide promoted isomerization of cheap D-fructose12. Although not high yielding (ca. 10% after crystallization) this one step process enables access to crystalline branched sugar 6 without chromatographic separation. Fleet group has more recently disclosed a new one-pot procedure13 to lactone 6 from Dglucose by similar isomerization of in situ formed Amadori ketose in yields up to 27%. The lactone 6 was prepared by the published procedure12,13 and then it was selectively 3,5-diacylated14 (Scheme 2) by the action of 2 equivalents of p-toluoyl chloride in the mixture of dichloromethane-pyridine (4:1) at -20 °C affording 3,5-di-O-toluoyl lactone 7 15 in 82% yield after crystallization. Under these conditions the formation of 2,3,5-tri-O-toluoyl derivative is minimized compared to older procedure15 and this contaminant is easily discarded from crude product by crystallization. The next step, partial reduction of lactone 7 to the desired lactol 5 was complicated by the presence of free 2-hydroxy group, which precludes reducing reagents susceptible to alcoholysis (like DIBAH). As the reduction of free lactone 6 to 2-C-methyl- D-ribose by sodium borohydride in water was reported16, we attempted the reduction of more hydrophobic lactone 7 by the treatment with sodium borohydride in THF/MeOH mixture, but desired diol 5 was isolated in less then 35% yields whereas overreduction of hemiacetal 5 was prevalent. As sodium bis(2-methoxyethoxy)aluminumhydride (SMEAH, Red-Al) modified by the introduction of ethoxy group simply by the addition of one equivalent of absolute ethanol to the Red-Al solution is well established reagent for partial reduction of lactones to lactols17, we presumed that free 2-hydroxy group could at least partly play the role of Red-Al modifier instead of ethanol. Thus the lactone 7 was treated with equimolar amount of Red-Al in toluene at -15 °C and desired diol 5 was isolated in satisfactory 57% yield. Unreacted lactone 7 was recovered in 8% yield and non-isolated remaining material was the product of overreduction. Crystalline diol 5 was then mesylated with methanesulfonyl chloride in the presence of triethylamine in dichloromethane to almost quantitatively afford epoxide 4. In accord with observations of its inventors11, 1,2-anhydro sugar 4 displayed enhanced stability towards hydrolysis, uncommon amongst other known glycal epoxides18 (mainly benzyl or TBS protected). The glycosylation of 6-chloro-7-deazapurine 8 with epoxide 4 in the presence of NaH as base in DMF/toluene afforded the desired protected 2'-Cmethyl ribonucleoside intermediate 9 in 58% yield (Scheme 3). Compound 9 was deprotected by the treatment with methanolic ammonia at room temperature affording free 2'-C-methylriboside 10 in 85% yield. With the key chlorodeazapurine nucleoside intermediate 10 in hand, the aqueous Suzuki cross-coupling reactions19 were conducted with a set of boronic acids affording 6-(het)aryl-7-deazapurine 2'-C-methyl ribosides 11a-11c, 11e and 11f in a single step in good to excellent yields (Scheme 4, Table I). An alternative nucleosidation route was used for the synthesis of 7-fluorinated 6-hetaryl-7-deazapurine 2'-C-methylribonucleosides. We anticipated that the corresponding protected 7-fluorinated 6-chloro-7-deazapurine 2'-C-methylribonucleoside might be accessible by Silyl-Hilbert- Johnson reaction, similarly to the synthesis of per-O-benzoyl 7-halogenated 6-chloro-7-deazapurine ribonucleosides by TMSOTf-catalyzed glycosylation20 of 5-halogenated 4-chloro-7H-pyrrolo[2,3-d]pyrimidines with 1-Oacetyl- 2,3,5-tri-O-benzoyl-ß-D-ribofuranose. Thus the reaction of 1,2,3,5- tetra-O-benzoyl-2-C-methyl-ß-D-ribofuranose 12 (Scheme 5) with 4-chloro- 5-fluoropyrrolo[2,3-d]pyrimidine 13 20a was performed in the presence of DBU and TMSOTf in acetonitrile at 70 °C to give the desired 2'-C-methylribonucleoside 14 in 21% unoptimized yield. This hydrophobic benzoylprotected 2'-C-methylribofuranoside 14 was directly reacted with 2-thiophene and 2-furane boronic acids under the conditions of aqueous Suzuki-Myiaura reaction19. Although the reaction mixtures were unhomogeneous, full conversions of starting chloride 14 were reached and only small degree of acyl deprotection was observed under quite harsh and basic reaction conditions. Crude reaction mixtures were directly deprotected using methanolic sodium methoxide in pyridine and, after purification by reverse phase chromatography, the desired 6-hetaryl-7-fluoro-7-deazapurine 2-Cmethylribonucleosides 15a and 15b were obtained in moderate 30 and 31% overall yields from 14. A synthetic path to 6-hetaryl-7-deazapurine arabinonucleosides was developed starting from 3',5'-O-disiloxane ribonucleoside 16 21 (Scheme 6, Table II). First, the 2'-hydroxyl group of riboside 16 was oxidized using Dess-Martin periodinane to ketone 17 in 88% yield. The application of Dess-Martin oxidation led to higher yield compared to CrO3 oxidation described in literature21. The follow up reduction of the 2'-oxo group by sodium borohydride in ethanol provided arabino-derivative 18 stereoselectively in high 87% yield. Silyl protecting group was cleaved by TBAF affording the unprotected 6-chloro-7-deazapurine arabinoside 19 in 83% yield. 6-Hetaryl-7-deazapurine arabinonucleosides were prepared by two different strategies. The first one was the Suzuki cross-coupling reaction of unprotected 6-chloro-7-deazapurine arabinofuranoside 19 with hetarylboronic acids using aqueous-phase conditions19 that led to 6-hetaryl-7-deazapurine arabinosides 21d and 21e in good yields after crystallization. Alternatively, 6-hetaryl-7-deazapurine arabinosides were synthesized starting from silyl-protected arabino-derivative 18 using Stille cross-coupling reaction with hetaryltributylstannanes. By this reaction, derivatives 20b and 20c were prepared in high yields. In the case of reaction of compound 18 and 2-thienyltributylstannane, concomitant isomeration of 3',5'-disiloxane-protected group to 2',3' position was observed. This rearrangement is known to be acid-catalyzed22. In this particular case the rearrangement was catalyzed by PdCl2(PPh3)4 as a Lewis acid. Final desilylations of 20b and 20c using TBAF led to target 6-hetaryl-7-deazapurine arabinonucleosides 21b and 21c in 72 and 77% yields, respectively. To get access to the 2'-deoxy-2'-fluoroarabino series, key starting materials: benzoyl-protected 6-chloro-7-deazapurine 2'-deoxy-2'-fluoroarabinonucleoside 23 23 and its 7-fluoro derivative 24 24 were prepared by stereoselective SN2 nucleobase-anion glycosylation with a-bromo sugar 25 (Scheme 7). Compound 23 was obtained in 72% yield by the glycosylation of 6-chloro-7-deazapurine 8 using Seela's protocol24 (KOH, TDA-1 {TDA-1 = tris[2-(2-methoxyethoxy)ethyl]amine)}, MeCN) instead of original one23 (NaH, MeCN). The reaction should be monitored and quenched as soon as the conversion is completed to avoid concomitant saponification of benzoyl groups under strongly basic reaction conditions. This observation was also noted in a recent related communication25. The bromide 25 26 was obtained by treatment of 2-deoxy-2-fluoro-1,3,5-tri-O-benzoyl-a-D-arabinofuranose 26 with 30% HBr in acetic acid. Palladium catalyzed cross-coupling reactions of chloride 23 (Scheme 8, Table III) with the corresponding (het)arylboronic acids, stannanes and trimethylaluminium provided the desired 6-substituted benzoyl-protected 2-deoxy-2-fluoroarabinonucleosides 27a-27e, 27g, 27h, which after deprotection by NaOMe in MeOH afforded final free 6-substituted 7-deazapurine 2'-deoxy-2'-fluoroarabinonucleosides 28a-28e, 28g, 28h. Similarly, analogous 7-fluoro-6-hetaryl-7-deazapurine 2'-deoxy-2'-fluoroarabinonucleosides 30b-30e (Scheme 9, Table IV) were prepared by crosscouplings of protected 6-chloro nucleoside 24 followed by deprotection of benzoylated intermediates 29b-29e. In summary, five types of sugar-modified 6-(het)aryl-7-deazapurine nucleosides were prepared: five examples of 6-(het)aryl-7-deazapurine 2'-C-methyl ribosides 11a-11c, 11e, 11f, two examples of 6-hetaryl- 7-fluoro-7-deazapurine 2'-C-methylribonucleosides 15a, 15b, four examples of 6-hetaryl-7-deazapurine arabinonucleosides 21b-21e, seven examples of 6-substituted 7-deazapurine 2'-deoxy-2'-fluoroarabinonucleosides 28a-28e, 28g, 28h and four examples of 7-fluoro-6-hetaryl-7-deazapurine 2'-deoxy-2'-fluoroarabinonucleosides 30b-30e. All of them were tested for in vitro cytostatic (HL60, HeLa S3, CCRF-CEM, A549, NCI-H23, Du145, PC3, HCT-116, HCT-15, Hs-578 and BT-549 cell-lines)5 and for anti-HCV 4 activity. None of them showed any considerable activity in any of these assays indicating that the cytostatic activity of 6-hetaryl-7-deazapurine nucleosides is only limited to ribonucleosides. Also the introduction of the 2'-C-methyl did not lead to selectivity toward inhibition of RNA-depending RNA polymerase of HCV. EXPERIMENTAL Melting points were determined on a Kofler block and are uncorrected. Optical rotations were measured at 25 °C, [a]D 20 values are given in 10-1 deg cm2 g-1. NMR spectra were measured at 400.1 MHz for 1H and 100.6 MHz for 13C nuclei, or at 499.8 MHz for 1H and 125.7 MHz for 13C, or at 600.1 MHz for 1H and 150.9 MHz for 13C in CDCl3 (TMS was used as internal standard), MeOH-d4 (referenced to the residual solvent signal), DMSO-d6 (referenced to the residual solvent signal), D2O (methanol as internal standard, referenced to CH3OH singlet 3.34 ppm and to CH3OH signal 49.5 ppm). 19F NMR spectra were recorded at 470.3 MHz. Chemical shifts are given in ppm (d-scale), coupling constants (J) in Hz. Complete assignment of all NMR signals was performed using a combination of H,H-COSY, H,H-ROESY, H,C-HSQC and H,C-HMBC experiments. High resolution mass spectra were measured using electrospray ionization. Reverse phase high performance flash chromatography (HPFC) purifications were performed with Biotage SP1 apparatus on KP-C18-HS columns. 6-Chloro-7-deazapurine (4-chloro-7H-pyrrolo[2,3-d]pyrimidine) 8 and 2-deoxy- 2-fluoro-1,3,5-tri-O-benzoyl-a-D-arabinofuranose 26 and 1,2,3,5-tetra-O-benzoyl-2-C-methyl- ß-D-ribofuranose 12 were purchased from Nucleo Chemisty Co. (Shenzhen, China). 2-C-Methyl-3,5-di-O-(4-methylbenzoyl)-D-ribono-1,4-lactone (7) Finely powdered 2-C-methylribonolactone 6 12,13 (20 g, 0.123 mol) was nearly fully dissolved in dichloromethane (400 ml)/pyridine (100 ml) by vigorous stirring at r.t., the mixture was cooled to -20 °C (bath temperature) and p-toluoyl chloride (34 ml, 0.257 mol) was dropwise added. The mixture was stirred at -20 °C for 2 h and then was left stand overnight at 5 °C (refrigerator). The volatiles were evaporated in vacuo and the residue was partitioned between AcOEt (500 ml) and aq. hydrochloric acid (3 M, 200 ml). Aqueous phase was reextracted with AcOEt (2 × 100 ml) and combined organic phases were washed with water (200 ml) and aq. NaHCO3 (sat., 100 ml), dried over MgSO4 and evaporated. The crude product was recrystallized from heptane-AcOEt (ca. 400 ml/80 ml) affording 7 (40.4 g, 82%) as white fine needles. M.p. 123-125 °C (heptane-AcOEt), lit.15 123 °C (diisopropylether); [a]D -81.5 (c 0.254, DMSO). 1H NMR (400.1 MHz, CDCl3): 1.65 (s, 3 H, CH3-2); 2.39, 2.41 (2 × s, 2 × 3 H, CH3-Tol); 2.95 (s, 1 H, OH); 4.56 (dd, 1 H, Jgem = 12.5, J5b,4 = 5.7, H-5b); 4.68 (dd, 1 H, Jgem = 12.5, J5a,4 = 3.8, H-5a); 4.93 (ddd, 1 H, J4,3 = 5.7, J4,5 = 5.7, 3.8, H-4); 5.38 (d, 1 H, J3,4 = 5.7, H-3); 7.20, 7.24 (2 × m, 2 × 2 H, H-m-Tol); 7.88, 7.94 (2 × m, 2 × 2 H, H-o-Tol). 13C NMR (100.6 MHz, CDCl3): 21.66, 21.72 (CH3-Tol); 23.17 (CH3-2); 62.74 (CH2-5); 72.69 (C-2); 74.07 (CH-3); 78.24 (CH-4); 125.56, 126.295 (C-i-Tol); 129.17, 129.32 (CH-m-Tol); 129.75, 130.00 (CH-o-Tol); 144.24, 144.90 (C-p-Tol); 165.49, 165.97 (CO); 174.63 (CO-1). MS (ESI) m/z: 421 (M + Na). HRMS (ESI) for C22H22O7Na [M + Na] calculated: 421.1258; found: 421.1255. 2-C-Methyl-3,5-di-O-(4-methylbenzoyl)-a,ß-D-ribofuranose (5) To a stirred solution of lactone 7 (8.81 g, 22.1 mmol) in toluene (150 ml) was dropwise added sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) (65 wt.% in toluene, 7 ml, 22.9 mmol) at -15 °C during 10 min. The mixture was stirred while the temperature (bath) was gradually increased to 0 °C within 3 h. The reaction was quenched by the addition of aq. hydrochloric acid (3 M, 100 ml) at 0 °C [Caution! Exothermic]. The mixture was filtered through celite, phases separated and aqueous phase was re-extracted with toluene (2 × 50 ml). Combined organics were washed with brine (100 ml), dried over MgSO4 and evaporated. Column chromatography of the residue on silica (hexanes-AcOEt, 6:1[arrow right]2:1) afforded unreacted starting material 7 (714 mg, 8%) and diol 5 (5.09 g, 57%) as a colorless oil which solidified on standing. The a/ß ratio according to 1H NMR in CDCl3 solution is ca. 4.5:1. Compound can be crystallized from heptane-AcOEt. M.p. 116-118 °C. a anomer: 1H NMR (499.8 MHz, CDCl3): 1.47 (s, 3 H, CH3-2); 2.38 and 2.40 (2 × s, 2 × 3 H, CH3-Tol); 3.12 (s, 1 H, OH-2); 4.05 (bd, 1 H, JOH,1 = 5.5, OH-1); 4.48 (dd, 1 H, Jgem = 11.4, J5b,4 = 4.8, H-5b); 4.63 (m, 1 H, H-4); 4.64 (dd, 1 H, Jgem = 11.4, J5a,4 = 3.6, H-5a); 5.10 (d, 1 H, J3,4 = 5.4, H-3); 5.13 (bd, 1 H, J1,OH = 5.5, H-1); 7.18 and 7.22 (2 × m, 2 × 2 H, H-m-Tol); 7.90 and 7.94 (2 × m, 2 × 2 H, H-o-Tol). 13C NMR (125.7 MHz, CDCl3): 21.61 and 21.66 (CH3-Tol); 23.43 (CH3-2); 64.00 (CH2-5); 76.34 (CH-3); 76.39 (C-2); 79.16 (CH-4); 100.67 (CH-1); 126.40 and 126.81 (C-i-Tol); 129.06 and 129.18 (CH-m-Tol); 129.70 and 129.83 (CH-o-Tol); 143.85 and 144.31 (C-p-Tol); 165.91 and 166.35 (CO). ß anomer: 1H NMR (499.8 MHz, CDCl3): 1.42 (s, 3 H, CH3-2); 2.35 and 2.41 (2 × s, 2 × 3 H, CH3-Tol); 2.43 (s, 1 H, OH-2); 3.72 (bd, 1 H, JOH,1 = 3.1, OH-1); 4.50 (m, 1 H, H-4); 4.54 (dd, 1 H, Jgem = 15.4, J5b,4 = 6.2, H-5b); 4.63 (dd, 1 H, Jgem = 15.4, J5a,4 = 3.6, H-5a); 5.22 (bd, 1 H, J1,OH = 3.1, H-1); 5.52 (d, 1 H, J3,4 = 6.9, H-3); 7.13 and 7.24 (2 × m, 2 × 2 H, H-m-Tol); 7.88 and 7.94 (2 × m, 2 × 2 H, H-o-Tol). 13C NMR (125.7 MHz, CDCl3): 19.89 (CH3-2); 21.59 and 21.66 (CH3-Tol); 65.53 (CH2-5); 76.87 (CH-3); 78.57 (CH-4); 79.71 (C-2); 102.87 (CH-1); 126.18 and 126.91 (C-i-Tol); 129.00 and 129.25 (CH-m-Tol); 129.70 and 129.83 (CH-o-Tol); 143.74 and 144.53 (C-p-Tol); 165.70 and 166.59 (CO). MS (ESI) m/z: 423 (M + Na). HRMS (ESI) for C22H24O7Na [M + Na] calculated: 423.1414; found: 423.1413. 1,2-Anhydro-2-C-methyl-3,5-di-O-(4-methylbenzoyl)-a-D-ribofuranose (4) To a stirred solution of diol 5 (2.00 g, 5 mmol) and triethylamine (1.74 ml, 12.5 mmol) in dichloromethane (20 ml) was dropwise added mesyl chloride (465 µl, 6 mmol) within 20 min at r.t.. The mixture was stirred for 1 h and then diluted with toluene (100 ml) and washed with phosphate buffer (pH 7; 75 ml). Aqueous phase was re-extracted with toluene (25 ml), combined organics (cloudy) were dried over Na2SO4 and evaporated in vacuo providing epoxide 1 as a colorless oil which was directly used in next. NMR spectra of epoxide 4 were recorded in "common" undried NMR grade CDCl3 (stabilized with silver wire); 1H spectrum revealed the presence of only single clean compound. 1H NMR (499.8 MHz, CDCl3): 1.56 (s, 3 H, CH3-2); 2.39, 2.43 (2 × s, 2 × 3 H, CH3-Tol); 4.25 (ddd, 1 H, J4,3 = 6.5, J4,5 = 5.1, 3.4, H-4); 4.46 (dd, 1 H, Jgem = 12.1, J5b,4 = 5.1, H-5b); 4.62 (dd, 1 H, Jgem = 12.1, J5a,4 = 3.4, H-5a); 5.15 (s, 1 H, H-1); 5.54 (d, 1 H, J3,4 = 6.5, H-3); 7.18, 7.26 (2 × m, 2 × 2 H, H-m-Tol); 7.88, 7.99 (2 × m, 2 × 2 H, H-o-Tol). 13C NMR (125.7 MHz, CDCl3): 14.08 (CH3-2); 21.64, 21.71 (CH3-Tol); 63.12 (CH2-5); 63.68 (C-2); 75.87 (CH-3); 78.16 (CH-4); 85.90 (CH-1); 126.15, 126.87 (C-i-Tol); 129.06, 129.19 (CH-m-Tol); 129.68, 130.01 (CH-o-Tol); 143.83, 144.46 (C-p-Tol); 166.07, 166.28 (CO). MS (ESI) m/z: 383 (M + H). HRMS (ESI) for C22H23O6 [M + H] calculated: 383.1489; found: 383.1486. 4-Chloro-7-[2-C-methyl-3,5-di-O-(4-methylbenzoyl)-ß-D-ribofuranosyl]- 7H-pyrrolo[2,3-d]pyrimidine (9) 6-Chloro-7-deazapurine 8 (691 mg, 4.5 mmol) was added to a stirred mixture of NaH (50% suspension in oil, 98 mg, 2.25 mmol) in dry DMF (10 ml) under argon at 0 °C. The mixture was stirred for 15 min, followed by the addition of a solution of epoxide 4 (prepared from 5 mmol of diol 5) in toluene (20 ml). The mixture was stirred for 18 h at r.t. and then diluted with AcOEt (100 ml) and washed with aq. KH2PO4 (0.3 M, 75 ml). Organic phase was washed with 5% brine (3 × 50 ml), dried over MgSO4, concentrated in vacuo and final chromatography on the column of silica (hexanes-AcOEt, 6:1) afforded protected nucleoside 9 as a colorless foam (1.41 g, 58%). 1H NMR (400.1 MHz, CDCl3): 1.08 (s, 3 H, CH3-2'); 2.42 and 2.44 (2 × s, 2 × 3 H, CH3-Tol); 3.21 (s, 1 H, OH-2'); 4.66 (dd, 1 H, Jgem = 12.1, J5'b,4' = 4.8, H-5'b); 4.73 (ddd, 1 H, J4',3' = 7.3, J4',5' = 4.8, 3.3, H-4'); 4.85 (dd, 1 H, Jgem = 12.1, J5'a,4' = 3.3, H-5'a); 5.65 (d, J3',4' = 7.3, H-3'); 6.44 (s, 1 H, H-1'); 6.61 (d, 1 H, J5,6 = 3.8, H-5); 7.23, 7.27 (2 × m, 2 × 2 H, H-m-Tol); 7.53 (d, 1 H, J6,5 = 3.8, H-6); 7.92-8.00 (m, 4 H, H-o-Tol); 8.65 (s, 1 H, H-2). 13C NMR (100.6 MHz, CDCl3): 21.08 (CH3-2); 21.67 and 21.71 (CH3-Tol); 63.06 (CH2-5'); 75.51 (CH-3'); 78.46 (CH-4'); 79.34 (C-2'); 91.62 (CH-1'); 100.62 (CH2-5); 118.24 (C-4a); 125.92 (C-i-Tol); 126.65 (CH-6); 126.79 (C-i-Tol); 129.22, 129.30 (CH-m-Tol); 129.69, 129.93 (CH-o-Tol); 144.10, 144.75 (C-p-Tol); 150.67 (C-4); 150.85 (CH-2); 152.58 (C-7a); 165.58, 166.25 (CO). MS (ESI) m/z: 536 (M + H), 558 (M + Na). HRMS (ESI) for C28H27N3O6Cl [M + H] calculated: 536.1583; found: 536.1573. 4-Chloro-7-(2-C-methyl-ß-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (10) Protected nucleoside 9 (281 mg, 0.52 mmol) was treated with methanolic ammonia (27 wt.%, 6 ml) at r.t. for 24 h. Volatiles were removed under reduced pressure and the residue was co-evaporated with silica and chromatographed on the column of silica (3% MeOH in CHCl3) affording free chloro nucleoside 10 (133 mg, 85%) as a colorless oil which solidified on standing. Compound was recrystallized from water as colorless prisms. M.p. 158-160 °C. [a]D -8.6 (c 0.360, DMSO). 1H NMR (400.1 MHz, D2O): 0.65 (s, 3 H, CH3-2'); 3.90 (dd, Jgem = 13.1, J5'b,4 = 3.8, H-5'b); 4.02-4.13 (m, 3 H, H-5'a, H-4', H-3'); 6.20 (s, 1 H, H-1'); 6.46 (d, 1 H, J5,6 = 3.8, H-5); 7.61 (d, 1 H, J6,5 = 3.8, H-6); 8.32 (s, 1 H, H-2). 13C NMR (100.6 MHz, D2O): 19.12 (CH3-2'); 60.63 (CH2-5'); 73.06 (CH-3'); 80.00 (C-2'); 82.45 (CH-4'); 91.65 (CH-1'); 101.36 (CH-5); 118.20 (C-4a); 128.20 (CH-6); 150.22 (C-4); 150.37 (CH-2); 152.11 (C-7a). MS (ESI) m/z: 300 (M + H), 322 (M + Na). HRMS (ESI) for C12H14N3O4ClNa [M + Na] calculated: 322.0565; found: 322.0567. For C12H14N3O4Cl calculated: 48.09% C, 4.71% H, 14.02% N; found: 48.05% C, 4.63% H, 13.78% N. 7-(2-C-Methyl-ß-D-ribofuranosyl)-4-(phenyl)-7H-pyrrolo[2,3-d]pyrimidine (11a) An argon purged mixture of compound 10 (157 mg, 0.52 mmol), phenylboronic acid (95 mg, 0.78 mmol), Na2CO3 (167 mg, 1.57 mmol), Pd(OAc)2 (5.9 mg, 0.026 mmol) and TPPTS (37 mg, 0.065 mmol) in water-MeCN (2:1, 3 ml) was stirred at 100 °C for 3 h. After cooling the mixture was neutralized by the addition of aq. HCl (3 M), volatiles were removed in vacuo and purification of the residue by reverse phase HPFC on C-18 (0[arrow right]100% MeOH in water) afforded product 11a (129 mg, 73%) as an amorphous tan solid. M.p. 177-179 °C. [a]D -26.3 (c 0.353, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 0.71 (s, 3 H, CH3); 3.70 (ddd, 1 H, Jgem = 12.3, J5'b,OH = 5.0, J5'b,4' = 3.2, H-5'b); 3.87 (ddd, 1 H, Jgem = 12.3, J5'a,OH = 5.0, J5'a,4' = 2.1, H-5'b); 3.92 (ddd, 1 H, J4',3' = 9.2, J4',5' = 3.2, 2.1, H-4'); 4.02 (dd, 1 H, J3',4' = 9.2, J3',OH = 7.0, H-3'); 5.207 (t, 1 H, JOH,3' = 5.0, OH-5'); 5.210 (d, 1 H, JOH,3' = 7.0, OH-3'); 5.23 (s, 1 H, OH-2'); 6.37 (s, 1 H, H-1'); 6.99 (d, 1 H, J5,6 = 3.8, H-5); 7.56 (m, 1 H, H-p-Ph); 7.59 (m, 2 H, H-m-Ph); 8.09 (d, 1 H, J6,5 = 3.8, H-6); 8.17 (m, 2 H, H-o-Ph); 8.89 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 19.90 (CH3); 59.75 (CH2-5'); 72.15 (CH-3'); 79.00 (C-2'); 82.60 (CH-4'); 90.73 (CH-1'); 100.96 (CH-5); 115.24 (C-4a); 127.89 (CH-6); 128.91 (CH-o-Ph); 129.19 (CH-m-Ph); 130.56 (CH-p-Ph); 137.74 (C-i-Ph); 151.25 (CH-2); 151.59 (C-7a); 156.34 (C-4). MS (ESI) m/z: 364 (M + Na). HRMS (ESI) for C18H20N3O4 [M + H] calculated: 342.1448; found: 342.1448. HRMS (ESI) for C18H19N3O4Na [M + Na] calculated: 364.1268; found: 364.1267. For C18H19N3O4.0.7CH4O calculated: 61.74% C, 6.04% H, 11.55% N; found: 62.01% C, 5.79% H, 11.06% N. 4-(Furan-2-yl)-7-(2-C-methyl-ß-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (11b) Compound 11b was prepared as described for 11a by the reaction of compound 10 (257 mg, 0.86 mg) and furane-2-boronic acid. Yield 230 mg (81%). Compound crystallized from MeOH as yellowish needles. M.p. 183-184 °C. [a]D -26.9 (c 0.309, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 0.68 (s, 3 H, CH3); 3.70 (ddd, 1 H, Jgem = 12.3, J5'b,OH = 5.0, J5'b,4' = 3.2, H-5'b); 3.86 (ddd, 1 H, Jgem = 12.3, J5'a,OH = 5.0, J5'a,4' = 2.1, H-5'b); 3.91 (ddd, 1 H, J4',3' = 9.1, J4',5' = 3.2, 2.1, H-4'); 4.01 (dd, 1 H, J3',4' = 9.1, J3',OH = 7.0, H-3'); 5.17 (d, 1 H, JOH,3' = 7.0, OH-3'); 5.18 (t, 1 H, JOH,3' = 5.0, OH-5'); 5.19 (s, 1 H, OH-2'); 6.33 (s, 1 H, H-1'); 6.79 (dd, 1 H, J4,3 = 3.5, J4,5 = 1.8, H-4-furyl); 7.04 (d, 1 H, J5,6 = 3.8, H-5); 7.47 (dd, 1 H, J3,4 = 3.5, J3,5 = 0.8, H-3-furyl); 8.057 (dd, 1 H, J5,4 = 1.8, J5,3 = 0.8, H-5-furyl); 8.062 (d, 1 H, J6,5 = 3.8, H-6); 8.78 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 19.74 (CH3); 59.66 (CH2-5'); 72.05 (CH-3'); 78.88 (C-2'); 82.52 (CH-4'); 90.56 (CH-1'); 101.09 (CH-5); 112.37 (C-4a); 112.84 (CH-4-furyl); 113.41 (CH-3-furyl); 127.74 (CH-6); 146.49 (CH-5-furyl); 146.58 (C-4); 151.15 (CH-2); 151.59 (C-7a); 152.65 (C-2-furyl). MS (ESI) m/z: 354 (M + Na). HRMS (ESI) for C16H18N3O5 [M + H] calculated: 332.1241; found: 332.1241. HRMS (ESI) for C16H17N3O5Na [M + Na] calculated: 354.1060; found: 354.1060. For C16H17N3O5 calculated: 58.00% C, 5.17% H, 12.68% N; found: 57.97% C, 4.95% H, 12.46% N. 7-(2-C-Methyl-ß-D-ribofuranosyl)-4-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (11c) Compound 11c was prepared as described for 11a by the reaction of compound 10 (133 mg, 0.44 mmol) and thiophene-2-boronic acid as a white powder. Yield 129 mg (84%). Compound was recrystallized from MeOH. M.p. 180-181 °C. [a]D -15.2 (c 0.309, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 0.69 (s, 3 H, CH3); 3.70 (ddd, 1 H, Jgem = 12.4, J5'b,OH = 5.0, J5'b,4' = 3.1, H-5'b); 3.87 (ddd, 1 H, Jgem = 12.4, J5'a,OH = 5.0, J5'a,4' = 2.1, H-5'b); 3.92 (ddd, 1 H, J4',3' = 9.1, J4',5' = 3.1, 2.1, H-4'); 4.02 (dd, 1 H, J3',4' = 9.1, J3',OH = 7.0, H-3'); 5.22 (d, 1 H, JOH,3' = 7.0, OH-3'); 5.226 (s, 1 H, OH-2'); 5.231 (t, 1 H, JOH,3' = 5.0, OH-5'); 6.33 (s, 1 H, H-1'); 7.15 (dd, 1 H, J5,6 = 3.8, J = 0.3, H-5); 7.30 (dd, 1 H, J4,5 = 5.0, J4,3 = 3.8, H-4-thienyl); 7.84 (dd, 1 H, J5,4 = 5.0, J5,3 = 1.1, H-5-thienyl); 8.09 (d, 1 H, J6,5 = 3.8, H-6); 8.16 (dd, 1 H, J3,4 = 3.8, J3,5 = 1.1, H-3-thienyl); 8.75 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 19.87 (CH3); 59.74 (CH2-5'); 72.13 (CH-3'); 79.04 (C-2'); 82.64 (CH-4'); 90.74 (CH-1'); 100.86 (CH-5); 112.80 (C-4a); 128.05 (CH-6); 129.40 (CH-4-thienyl); 129.87 (CH-3-thienyl); 131.03 (CH-5-thienyl); 142.68 (C-2-thienyl); 150.37 (C-4); 151.03 (CH-2); 151.64 (C-7a). MS (ESI) m/z: 348 (M + H), 370 (M + Na). HRMS (ESI) for C16H18N3O4S [M + H] calculated: 348.1012; found: 348.1013. HRMS (ESI) for C16H17N3O4SNa [M + Na] calculated: 370.0832; found: 370.0831. For C16H17N3O4S calculated: 55.32% C, 4.93% H, 12.10% N; found: 55.14% C, 4.72% H, 11.84% N. 7-(2-C-Methyl-ß-D-ribofuranosyl)-4-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (11e) Compound 11e was prepared as described for 11a by the reaction of compound 10 (150 mg, 0.5 mmol) and thiophene-3-boronic acid as an off-white foamy solid. Yield 172 mg (99%). M.p. 154-156 °C. [a]D -24.0 (c 0.329, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 0.69 (s, 3 H, CH3); 3.71 (ddd, 1 H, Jgem = 12.4, J5'b,OH = 5.0, J5'b,4' = 3.1, H-5'b); 3.87 (ddd, 1 H, Jgem = 12.4, J5'a,OH = 5.0, J5'a,4' = 2.1, H-5'b); 3.92 (ddd, 1 H, J4',3' = 9.1, J4',5' = 3.1, 2.1, H-4'); 4.02 (dd, 1 H, J3',4' = 9.1, J3',OH = 7.0, H-3'); 5.195 (d, 1 H, JOH,3' = 7.0, OH-3'); 5.21 (s, 1 H, OH-2'); 5.22 (t, 1 H, JOH,3' = 5.0, OH-5'); 6.35 (s, 1 H, H-1'); 7.12 (d, 1 H, J5,6 = 3.8, H-5); 7.74 (dd, 1 H, J5,4 = 5.1, J5,2 = 2.9, H-5-thienyl); 7.95 (dd, 1 H, J4,5 = 5.1, J4,2 = 1.3, H-4-thienyl); 8.08 (d, 1 H, J6,5 = 3.8, H-6); 8.53 (dd, 1 H, J2,5 = 2.9, J2,4 = 1.3, H-2-thienyl); 8.82 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 19.84 (CH3); 59.72 (CH2-5'); 72.12 (CH-3'); 78.98 (C-2'); 82.58 (CH-4'); 90.66 (CH-1'); 100.96 (CH-5); 114.30 (C-4a); 128.05 (CH-6); 127.38 (CH-5-thienyl); 127.65 (CH-4-thienyl); 127.68 (CH-6); 128.78 (CH-2-thienyl); 140.13 (C-3-thienyl); 151.15 (CH-2); 151.62, 151.66 (C-4,7a). MS (ESI) m/z: 348 (M + H), 370 (M + Na). HRMS (ESI) for C16H18N3O4S [M + H] calculated: 348.10125; found: 348.10125. HRMS (ESI) for C16H17N3O4SNa [M + Na] calculated: 370.0832; found: 370.0832. For C16H17N3O4S calculated: 55.32% C, 4.93% H, 12.10% N; found: 55.27% C, 4.78% H, 11.80% N. 7-(2-C-Methyl-ß-D-ribofuranosyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (11f) Compound 11f was prepared as described for 11a by the reaction of compound 10 (157 mg, 0.52 mmol) and pyridine-3-boronic acid. Yield 134 mg (75%). Compound crystallized from MeOH tan solid. M.p. 191-193 °C. [a]D -20.3 (c 0.310, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 0.71 (s, 3 H, CH3); 3.71 (ddd, 1 H, Jgem = 12.4, J5'b,OH = 5.0, J5'b,4' = 3.2, H-5'b); 3.87 (ddd, 1 H, Jgem = 12.4, J5'a,OH = 5.0, J5'a,4' = 2.1, H-5'b); 3.93 (ddd, 1 H, J4',3' = 9.1, J4',5' = 3.2, 2.1, H-4'); 4.03 (dd, 1 H, J3',4' = 9.1, J3',OH = 7.0, H-3'); 5.23 (t, 1 H, JOH,3' = 5.0, OH-5'); 5.24 (d, 1 H, JOH,3' = 7.0, OH-3'); 5.25 (s, 1 H, OH-2'); 6.37 (s, 1 H, H-1'); 7.05 (d, 1 H, J5,6 = 3.8, H-5); 7.62 (dd, 1 H, J5,4 = 8.0, J5,6 = 4.8, H-5-py); 8.13 (d, 1 H, J6,5 = 3.8, H-6); 8.52 (ddd, 1 H, J4,5 = 8.0, J4,2 = 2.3, J4,6 = 1.7, H-4-py); 8.74 (bd, 1 H, J6,5 = 4.8, H-6-py); 8.93 (s, 1 H, H-2); 9.32 (bs, 1 H, H-2-py). 13C NMR (125.7 MHz, DMSO-d6): 19.94 (CH3); 59.78 (CH2-5'); 72.18 (CH-3'); 79.05 (C-2'); 82.68 (CH-4'); 90.81 (CH-1'); 100.76 (CH-5); 115.58 (C-4a); 124.42 (CH-5-py); 128.49 (CH-6); 133.44 (C-3-py); 136.43 (CH-4-py); 149.52 (CH-2-py); 151.23 (CH-6-py); 151.36 (CH-2); 151.56 (C-7a); 153.91 (C-4). MS (ESI) m/z: 365 (M + Na). HRMS (ESI) for C17H19N4O4 [M + H] calculated: 343.1401; found: 343.1401. HRMS (ESI) for C17H18N4O4Na [M + Na] calculated: 365.12203; found: 365.12200. For C17H18N4O4.0.2H2O calculated: 59.02% C, 5.36% H, 16.19% N; found: 58.92% C, 5.11% H, 15.96% N. 4-Chloro-5-fluoro-7-(2,3,5-tri-O-benzoyl-2-C-methyl-ß-D-ribofuranosyl)- 7H-pyrrolo[2,3-d]pyrimidine (14) To a mixture of 6-chloro-7-fluoro-7-deazapurine 13 20a (577 mg, 3.36 mmol) and per- O-benzoyl-2-C-methylribofuranose 12 (1.68 g, 2.90 mmol) and DBU (1.3 ml, 8.71 mmol) in dry CH3CN (20 ml) was dropwise added TMSOTf (2.1 ml, 11.63 mmol). The mixture was stirred at 70 °C for 24 h, cooled to r.t. diluted with CHCl3 (50 ml) and washed with aq. NaHCO3 (sat., 50 ml). Aqueous phase was re-extracted with CHCl3 (2 × 10 ml), combined organics were dried over MgSO4 and evaporated. The residue was purified twice by column chromatography on silica (hexanes-AcOEt, 10:1) affording product 14 as a colorless foam (380 mg, 21%). 1H NMR (499.8 MHz, CDCl3): 1.60 (s, 3 H, CH3); 4.70 (td, 1 H, J4',3' = 5.7, J4',5' = 5.7, 3.5, H-4'); 4.87 (dd, 1 H, Jgem = 12.3, J5'b,4' = 5.7, H-5'b); 4.93 (dd, 1 H, Jgem = 12.3, J5'a,4' = 3.5, H-5'a); 5.975 (d, 1 H, J3',4' = 5.7, H-3'); 6.97 (d, 1 H, JH,F = 0.9, H-1'); 7.33 (m, 2 H, H-m-Bz); 7.36 (d, 1 H, JH,F = 2.4, H-6); 7.46 (m, 4 H, H-m-Bz); 7.54, 7.59, 7.61 (3 × m, 3 × 1 H, H-p-Bz); 7.95, 8.10, 8.11 (3 × m, 3 × 2 H, H-o-Bz); 8.76 (s, 1 H, H-2). 13C NMR (125.7 MHz, CDCl3): 17.80 (CH3); 63.28 (CH2-5'); 75.48 (CH-3'); 80.09 (CH-4'); 84.83 (C-2'); 88.39 (CH-1'); 107.96 (d, JC,F = 13.8, C-4a); 110.58 (d, JC,F = 27.1, CH-6); 128.49, 128.54, 128.57 (CH-m-Bz); 128.65, 129.49, 129.61 (C-i-Bz); 129.74, 129.83, 129.93 (CH-o-Bz); 133.41, 133.65, 133.72 (CH-p-Bz); 141.39 (d, JC,F = 254.2, C-5); 146.82 (C-7a); 151.02 (d, JC,F = 3.9, C-4); 151.83 (CH-2); 165.05, 165.34, 166.31 (CO). MS (ESI) m/z: 630 (M + H), 652 (M + Na). HRMS (ESI) for C33H25ClFN3O7Na [M + Na] calculated: 652.1263; found: 652.1260. 5-Fluoro-4-(furan-2-yl)-7-(2-C-methyl-ß-D-ribofuranosyl)- 7H-pyrrolo[2,3-d]pyrimidine (15a) To an argon purged mixture of compound 14 (185 mg, 0.29 mmol), furane-2-boronic acid (41 mg, 0.37 mmol), Na2CO3 (94 mg, 0.89 mmol) was added a pre-prepared solution of Pd(OAc)2 (3 mg, 0.013 mmol) and TPPTS (21 mg, 0.037 mmol) in water/CH3CN (2:1, 2.5 ml). The reaction mixture was stirred at 100 °C for 3 h. The volatiles were removed under reduced pressure and the residue was twice co-evaporated with absolute ethanol, dissolved in pyridine (2 ml), followed by addition of MeONa (1 M in MeOH, 0.9 ml, 0.9 mmol). After 15 min the the mixture was desalted with Dowex 50 (pyridinium form) and after removal of volatiles final reverse phase chromatography on C-18 (0[arrow right]100% MeOH in water) afforded product 15a as a colorless solid (31 mg, 30%). M.p. 222-224 °C. [a]D -16.7 (c 0.132, DMSO). 1H NMR (600.1 MHz, CD3OD): 0.86 (s, 3 H, CH3); 3.86 (m, 1 H, H-5'b); 4.01-4.05 (m, 2 H, H-4',5'a); 4.13 (d, 1 H, J3',4' = 8.9, H-3'); 6.51 (d, 1 H, JH,F = 1.7, H-1'); 6.73 (dd, 1 H, J4,3 = 3.6, J4,5 = 1.7, H-4-furyl); 7.54 (dd, 1 H, J3,4 = 3.6, J3,5 = 0.8, H-3-furyl); 7.87 (dd, 1 H, J5,4 = 1.7, J5,3 = 0.8, H-5-furyl); 7.96 (d, 1 H, JH,F = 2.0, H-6); 8.73 (s, 1 H, H-2). 13C NMR (150.9 MHz, CD3OD): 19.84 (CH3); 60.92 (CH2-5'); 73.41 (CH-3'); 80.51 (C-2'); 83.94 (CH-4'); 91.97 (CH-1'); 103.55 (d, JC,F = 15.7, C-4a); 111.52 (d, JC,F = 31.4, CH-6); 113.82 (CH-4-furyl); 116.50 (d, JC,F = 9.6, CH-3-furyl); 143.31 (d, JC,F = 249.9, C-5); 147.54 (CH-5-furyl); 147.73 (d, JC,F = 3.8, C-4); 148.34 (d, JC,F = 3.2, C-7a); 151.87 (C-2-furyl); 152.37 (CH-2). 19F NMR (470.3 MHz, DMSO-d6): -162.07. MS (ESI) m/z: 350 (M + H), 372 (M + Na). HRMS (ESI) for C16H16FN3O5Na [M + Na] calculated: 372.0971; found: 372.0965. 5-Fluoro-7-(2-C-methyl-ß-D-ribofuranosyl)-4-(thiophen-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (15b) Compound 15b was prepared as described for 15a from compound 14 (182 mg, 0.29 mmol) and thiophene-2-boronic acid. Yield 33 mg (31%). Colorless solid. M.p. 146-148 °C. 1H NMR (600.1 MHz, CD3OD): 0.87 (s, 3 H, CH3); 3.86 (m, 1 H, H-5'b); 4.01-4.05 (m, 2 H, H-4',5'a); 4.13 (d, 1 H, J3',4' = 9.0, H-3'); 6.51 (d, 1 H, JH,F = 1.9, H-1'); 7.25 (dd, 1 H, J4,5 = 5.0, J4,3 = 3.8, H-4-thienyl); 7.73 (dd, 1 H, J5,4 = 5.0, J5,3 = 1.0, H-5-thienyl); 7.96 (d, 1 H, JH,F = 1.9, H-6); 8.13 (dd, 1 H, J3,4 = 3.8, J3,5 = 1.0, H-3-thienyl); 8.69 (s, 1 H, H-2). 13C NMR (150.9 MHz, CD3OD): 19.86 (CH3); 60.94 (CH2-5'); 73.42 (CH-3'); 80.51 (C-2'); 83.92 (CH-4'); 92.02 (CH-1'); 103.95 (d, JC,F = 15.4, C-4a); 111.16 (d, JC,F = 32.1, 3.4, CH-6); 129.74 (d, JC,F = 2.3, CH-4-thienyl); 131.65 (d, JC,F = 16.5, CH-3-thienyl); 132.12 (CH-5-thienyl); 143.00 (d, JC,F = 1.1, C-2-thienyl); 143.36 (d, JC,F = 247.5, C-5); 148.39 (d, JC,F = 3.1, C-7a); 152.45 (d, JC,F = 3.9, C-4); 152.46 (CH-2). 19F NMR (470.3 MHz, DMSO-d6): -161.16. MS (ESI) m/z: 366 (M + H), 388 (M + Na). HRMS (ESI) for C16H16FN3O4SNa [M + Na] calculated: 388.0743; found 388.0736. 4-Chloro-7-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-ß-D-erythro-pentofuran-2-ulosyl]- 7H-pyrrolo[2,3-d]pyrimidine (17) Dess-Martin periodinane (3.61 g, 8.51 mmol) was dissolved in anhydrous dichloromethane (20 ml) and the solution was cooled to 0 °C. Then the solution of compound 16 (1.50 g, 2.83 mmol) in anhydrous dichloromethane (10 ml) was added. The reaction mixture was stirred at 0 °C for 5 min and then was allowed to warm to r.t. and stirred overnight. Then the reaction mixture was diluted with chloroform (50 ml) and the solution of Na2S2O3.5H2O (19.20 g) in aq. NaHCO3 (sat., 150 ml) was added. The organic phase was extracted with water, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica (hexane-EtOAc, 10:1) to give the ketone 17 (1.31 g, 88%) as a white solid. 1H NMR (500.0 MHz, CDCl3): 1.05-1.22 (m, 28 H, (CH3)2CHSi); 4.03 (dt, 1 H, J4',3' = 9.8, J4',5' = 2.9, H-4'); 4.14, 4.20 (2 × dd, 2 × 1 H, Jgem = 13.1, J5',4' = 2.9, H-5'); 5.52 (d, 1 H, J3',4' = 9.8, H-3'); 5.74 (d, 1 H, J1',3' = 0.6, H-1'); 6.65 (d, 1 H, J5,6 = 3.7, H-5); 7.26 (d, 1 H, J6,5 = 3.7, H-6); 8.49 (s, 1 H, H-2). 13C NMR (125.7 MHz, CDCl3): 12.44, 12.54, 12.94, 13.47 ((CH3)2CHSi); 16.75, 16.78, 16.82, 16.90, 17.20, 17.27, 17.29, 17.32 ((CH3)2CHSi); 60.94 (CH2-5'); 72.50 (CH-3'); 78.60 (CH-4'); 82.43 (CH-1'); 101.23 (CH-5); 118.54 (C-4a); 129.17 (CH-6); 150.81 (C-7a); 150.90 (CH-2); 152.69 (C-4); 206.07 (C-2'). MS (ESI) m/z: 548 [M + Na], 550 [M + 2 + Na], 558 [M + H + MeOH], 560 [M + H + MeOH], 580 [M + Na + MeOH], 582 [M + 2 Na + MeOH]. HRMS (ESI) for C23H36O5N3ClNaSi2 [M + Na] calculated: 548.1774; found: 548.1772. 4-Chloro-7-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-ß-D-arabinofuranosyl]- 7H-pyrrolo[2,3-d]pyrimidine (18) A solution of sodium borohydride (173 mg, 4.58 mmol) in ethanol (99%, 30 ml) was slowly added to a solution of ketone 17 (1.20 g, 2.28 mmol) in ethanol (99%, 50 ml) at 0 °C. The reaction mixture was stirred at r.t. for 1 h. The reaction was quenched with aq. NH4Cl (sat., 15 ml). The reaction mixture was extracted with EtOAc (100 ml). The organic phase was washed with water, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica (hexane-EtOAc, 10:1) to give the arabino-derivative 18 (1.05 g, 87%) as a white solid. 1H NMR (500.0 MHz, CDCl3): 0.97-1.17 (m, 28 H, (CH3)2CHSi); 2.96 (bs, 1 H, OH-2'); 3.85 (dt, 1 H, J4',3' = 8.4, J4',5' = 3.0, H-4'); 4.05, 4.11 (2 × dd, 2 × 1 H, Jgem = 13.0, J5',4' = 3.0, H-5'); 4.54 (dd, 1 H, J3',4' = 8.4, J3',2' = 7.8, H-3'); 4.66 (dd, 1 H, J2',3' = 7.8, J2',1' = 6.3, H-2'); 6.43 (d, 1 H, J1',2' = 6.3, H-1'); 6.63 (d, 1 H, J5,6 = 3.7, H-5); 7.70 (d, 1 H, J6,5 = 3.7, H-6); 8.57 (s, 1 H, H-2). 13C NMR (125.7 MHz, CDCl3): 12.42, 13.00, 13.01, 13.49 ((CH3)2CHSi); 16.86, 16.90, 16.94, 17.04, 17.31, 17.33, 17.37, 17.49 ((CH3)2CHSi); 60.01 (CH2-5'); 73.68 (CH-3'); 76.98 (CH-2'); 80.85 (CH-4'); 83.80 (CH-1'); 100.03 (CH-5); 118.47 (C-4a); 128.34 (CH-6); 150.40 (CH-2); 150.85 (C-7a); 152.37 (C-4). MS (ESI) m/z: 528 [M + H], 530 [M + 2 + H], 550 [M + Na], 552 [M + 2 + Na]. HRMS (ESI) for C23H39O5N3ClSi2 [M + H] calculated: 528.2111; found: 528.2112. 4-Chloro-7-(ß-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (19) Compound 18 (363 mg, 0.69 mmol) was dissolved in anhydrous THF (10 ml) and cooled to 0 °C. Then, the solution of tetrabutylammonium fluoride (433 mg, 1.37 mmol) in anhydrous THF (1.4 ml) was slowly added. The reaction mixture was stirred at r.t. for 2 h. The reaction mixture was evaporated under reduced pressure and purified by column chromatography on silica (4% MeOH in CHCl3) to give the free nucleoside 19 (163 mg, 83%) as a white solid. M.p. 163-165 °C. 1H NMR (500.0 MHz, DMSO-d6): 3.64 (dt, 1 H, Jgem = 11.8, J5'b,OH = J5'b,4' = 5.3, H-5'b); 3.71 (ddd, 1 H, Jgem = 11.8, J5'a,OH = 5.3, J5'a,4' = 3.9, H-5'a); 3.79 (ddd, 1 H, J4',5' = 5.3, 3.9, J4',3' = 4.7, H-4'); 4.11 (dt, 1 H, J3',2' = 5.0, J3',OH = J3',4' = 4.7, H-3'); 4.19 (ddd, 1 H, J2',OH = 5.5, J2',1' = 5.2, J2',3' = 5.0, H-2'); 5.08 (t, 1 H, JOH,5' = 5.3, OH-5'); 5.50 (d, 1 H, JOH,2' = 5.5, OH-2'); 5.52 (d, 1 H, JOH,3' = 4.7, OH-3'); 6.55 (d, 1 H, J1',2' = 5.2, H-1'); 6.67 (dd, 1 H, J5,6 = 3.7, 5J = 0.4, H-5); 7.88 (d, 1 H, J6,5 = 3.7, H-6); 8.64 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.85 (CH2-5'); 74.83 (CH-3'); 76.15 (CH-2'); 83.97, 83.98 (CH-1',4'); 98.61 (CH-5); 117.14 (C-4a); 130.66 (CH-6); 150.40 (CH-2); 150.53 (C-4); 150.97 (C-7a). MS (ESI) m/z: 284 [M-H], 286 [M + 2 - H]. HRMS (ESI) for C11H11O4N3Cl [M - H] calculated: 284.0444; found: 284.0444. 4-(Furan-2-yl)-7-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-ß-D-arabinofuranosyl]- 7H-pyrrolo[2,3-d]pyrimidine (20b) An argon purged mixture of compound 18 (220 mg, 0.42 mmol), 2-(tributylstannyl)furane (230 mg, 0.64 mmol) and PdCl2(PPh3)2 (15 mg, 0.021 mmol) in DMF (2 ml) was stirred at 100 °C for 2 h. After cooling volatiles were removed in vacuo and the residue was several times co-evaporated with toluene. Column chromatography on silica (hexanes-AcOEt, 10:1[arrow right]3:1) afforded product 20b (230 mg, 99%) as a colorless oil. 1H NMR (400.0 MHz, CDCl3): 0.97-1.15 (m, 28 H, (CH3)2CHSi); 3.62 (bs, 1 H, OH-2'); 3.84 (dt, 1 H, J4',3' = 8.0, J4',5' = 3.2, H-4'); 4.04-4.05 (m, 2 H, H-5'); 4.60-4.70 (m, 2 H, H-2', H-3'); 6.40 (d, 1 H, J1',2' = 6.4, H-1'); 6.63 (dd, 1 H, J = 3.6, J = 2.0, H-4-furyl); 7.03 (d, 1 H, J5,6 = 3.6, H-5); 7.44 (m, 1 H, H-3-furyl); 7.64 (d, 1 H, J6,5 = 3.6, H-6); 7.71 (m, 1 H, H-5-furyl); 8.74 (s, 1 H, H-2). MS (ESI) m/z: 560 [M + H], 582 [M + Na]. HRMS (ESI) for C27H42O6N3Si2 [M + H] calculated: 560.2607; found: 560.2608. 4-(Thiophene-2-yl)-7-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-ß-D-arabinofuranosyl]- 7H-pyrrolo[2,3-d]pyrimidine (20c) and 4-(Thiophene-2-yl)-7-[2,3-O- (tetraisopropyldisiloxan-1,3-diyl)-ß-D-arabinofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine (22c) An argon purged mixture of compound 18 (220 mg, 0.42 mmol), 2-(tributylstannyl)- thiophene (240 mg, 0.64 mmol) and PdCl2(PPh3)2 (15 mg, 0.021 mmol) in DMF (2 ml) was stirred at 100 °C for 2 h. After cooling volatiles were removed in vacuo and the residue was several times co-evaporated with toluene. HPFC of the residue on silica (0[arrow right]100% EtOAc in hexane) afforded product 20c (32 mg, 13%) as a colourless oil, product 22c (32 mg, 13%) as a colourless oil and the mixture of compounds 20c and 22c (146 mg, 61%). The overall yield of the cross-coupling products 20c and 22c is 210 mg (88%). 20c: 1H NMR (400.0 MHz, CDCl3): 1.00-1.15 (m, 28 H, (CH3)2CHSi); 3.55 (bs, 1 H, OH-2'); 3.83 (dt, 1 H, J4',3' = 7.6, J4',5' = 3.2, H-4'); 4.01-4.10 (m, 2 H, H-5'); 4.28-4.70 (m, 2 H, H-2', H-3'); 6.41 (d, 1 H, J1',2' = 6.0, H-1'); 7.89 (d, 1 H, J5,6 = 3.6, H-5); 7.22 (dd, 1 H, J = 5.2, J = 3.6, H-4-thienyl); 7.57 (dd, 1 H, J = 5.2, J = 1.2, H-3-thienyl); 7.67 (d, 1 H, J5,6 = 4.0, H-6); 7.98 (d, 1 H, J = 3.2, H-3-thienyl); 8.74 (s, 1 H, H-2). MS (ESI) m/z: 576 [M + H], 598 [M + Na]. HRMS (ESI) for C27H42O5N3SSi2 [M + H] calculated: 576.2378; found: 576.2379. 22c: 1H NMR (400.0 MHz, CDCl3): 0.92-1.10 (m, 28 H, (CH3)2CHSi); 3.74 (bs, 1 H, OH-5'); 3.87 (bd, 1 H, J5'a,5'b = 12.4, H-5'a); 3.96 (dt, 1 H, J4',3' = 8.8, J4',5' = 2.0, H-4'); 4.08 (dd, 1 H, J5'a,5'b = 12.0, J4',5' = 2.0, H-5'b); 4.70 (dd, 1 H, J4',3' = 8.0, J2',3' = 7.6, H-2'); 4.85 (t, 1 H, J1',2' = J2',3' = 7.6, H-3'); 6.54 (d, 1 H, J1',2' = 7.2, H-1'); 6.85 (d, 1 H, J5,6 = 3.6, H-5); 7.22 (dd, 1 H, J = 5.2, J = 3.6, H-4-thienyl); 7.42 (d, 1 H, J5,6 = 3.6, H-6); 7.56 (dd, 1 H, J = 4.8, J = 0.8, H-5-thienyl); 7.96 (bs, 1 H, H-3-thienyl); 8.78 (s, 1 H, H-2). MS (ESI) m/z: 576 [M + H], 598 [M + Na]. HRMS (ESI) for C27H42O5N3SSi2 [M + H] calculated: 576.2378; found: 576.2378. 4-(Furan-2-yl)-7-(ß-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (21b) Deprotection of nucleoside 20b (200 mg, 0.36 mmol) was performed as described for compound 19. White crystalline solid (82 mg, 72%). Compound was recrystallized (H2O- methanol, 2:1). M.p. 228-230 °C. [a]D 20 -19.6 (c 0.204, DMSO). IR (ATR): 3509, 1601, 1572, 1466, 1249, 1069, 1018 cm-1. 1H NMR (500.0 MHz, DMSO-d6): 3.64 (dt, 1 H, Jgem = 11.6, J5'b,OH = J5'b,4' = 5.3, H-5'b); 3.71 (ddd, 1 H, Jgem = 11.6, J5'a,OH = 5.3, J5'a,4' = 4.1, H-5'a); 3.79 (ddd, 1 H, J4',5' = 5.3, 4.1, J4',3' = 4.7, H-4'); 4.12 (q, 1 H, J3',2' = J3',OH = J3',4' = 4.7, H-3'); 4.17 (ddd, 1 H, J2',OH = 5.6, J2',1' = 5.3, J2',3' = 4.7, H-2'); 5.07 (t, 1 H, JOH,5' = 5.3, OH-5'); 5.51 (d, 1 H, JOH,2' = 5.6, OH-2'); 5.52 (d, 1 H, JOH,3' = 4.7, OH-3'); 6.60 (d, 1 H, J1',2' = 5.1, H-1'); 6.78 (dd, 1 H, J4,3 = 3.5, J4,5 = 1.7, H-4-furyl); 7.00 (d, 1 H, J5,6 = 3.7, H-5); 7.45 (dd, 1 H, J3,4 = 3.5, J3,5 = 0.8, H-3-furyl); 7.81 (d, 1 H, J6,5 = 3.8, H-6); 8.06 (dd, 1 H, J5,4 = 1.7, J5,3 = 0.8, H-5-furyl); 8.75 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 61.15 (CH2-5'); 75.35 (CH-3'); 76.17 (CH-2'); 83.34 (CH-1'); 83.94 (CH-4'); 100.11 (CH-5); 112.44 (C-4a); 112.78 (CH-4-furyl); 113.17 (CH-3-furyl); 130.17 (CH-6); 146.18 (C-4); 146.35 (CH-5-furyl); 150.88 (CH-2); 151.91 (C-7a); 152.79 (C-2-furyl). MS (ESI) m/z: 318 [M + H], 340 [M + Na]. HRMS (ESI) for C15H15O5N3Na [M + Na] calculated: 340.0904; found: 340.0904. For C15H15O5N3 calculated: 56.78% C, 4.76% H, 13.24% N; found: 56.45% C, 4.75% H, 12.82% N. 4-(Thiophene-2-yl)-7-(ß-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (21c) Deprotection of the 20c and 22c mixture (180 mg, 0.31 mmol) was performed as described for compound 19. Pale yellow needles (80 mg, 77%). Compound was recrystallized (H2O- methanol, 2:1). M.p. 225-227 °C. [a]D 20 -15.7 (c 0.172, DMSO). IR (ATR): 3126, 1567, 1439, 1072, 1023 cm-1. 1H NMR (499.8 MHz, DMSO-d6): 3.65 (dt, 1 H, Jgem = 11.7, J5'b,OH = J5'b,4' = 5.3, H-5'b); 3.72 (ddd, 1 H, Jgem = 11.7, J5'a,OH = 5.3, J5'a,4' = 4.3, H-5'a); 3.79 (ddd, 1 H, J4',5' = 5.3, 4.3, J4',3' = 4.6, H-4'); 4.13 (dt, 1 H, J3',2' = 5.1, J3',OH = J3',4' = 4.6, H-3'); 4.19 (dt, 1 H, J2',OH = 6.0, J2',1' = J2',3' = 5.1, H-2'); 5.09 (t, 1 H, JOH,5' = 5.3, OH-5'); 5.522 (d, 1 H, JOH,2' = 6.0, OH-2'); 5.523 (d, 1 H, JOH,3' = 4.6, OH-3'); 6.61 (d, 1 H, J1',2' = 5.1, H-1'); 7.10 (d, 1 H, J5,6 = 3.8, H-5); 7.31 (dd, 1 H, J4,5 = 5.0, J4,3 = 3.8, H-4-thienyl); 7.84 (d, 1 H, J6,5 = 3.8, H-6); 7.85 (dd, 1 H, J5,4 = 5.0, J5,3 = 1.0, H-5-thienyl); 8.15 (dd, 1 H, J3,4 = 3.8, J3,5 = 1.0, H-3-thienyl); 8.73 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 61.07 (CH2-5'); 75.21 (CH-3'); 76.19 (CH-2'); 83.43 (CH-1'); 83.91 (CH-4'); 99.72 (CH-5); 112.74 (C-4a); 129.21 (CH-4-thienyl); 129.49 (CH-3-thienyl); 130.33 (CH-6); 130.69 (CH-5-thienyl); 142.76 (C-2-thienyl); 149.82 (C-4); 150.66 (CH-2); 151.85 (C-7a). MS (ESI) m/z: 334 [M + H]. HRMS (ESI) for C15H16O4N3S [M + H] calculated: 334.0856; found: 334.0856. For C15H15O4N3S. 1.5H2O calculated: 49.99% C, 5.03% H, 11.66% N; found: 50.30% C, 4.98% H, 11.45% N. 4-(Furan-3-yl)-7-(ß-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (21d) An argon purged mixture of compound 19 (130 mg, 0.45 mmol), furane-2-boronic acid (63 mg, 0.56 mmol), Na2CO3 (144 mg, 1.36 mmol), Pd(OAc)2 (5.1 mg, 0.023 mmol) and TPPTS (39 mg, 0.069 mmol) in water-MeCN (2:1, 2 ml) was stirred at 100 °C for 3 h. After cooling the mixture was neutralized by the addition of aq. HCl (3 M), volatiles were removed in vacuo and purification of the residue by reverse phase HPFC on C-18 (0[arrow right]100% MeOH in water) and crystallization (H2O-methanol, 2:1) afforded product 21d (112 mg, 78%) as a white crystalline solid. M.p. 212-214 °C. [a]D 20 -13.9 (c 0.245, DMSO). IR (ATR): 3494, 1579, 1461, 1165, 1074, 1022 cm-1. 1H NMR (499.8 MHz, DMSO-d6): 3.64, 3.71 (2 × dt, 2 × 1 H, Jgem = 11.8, J5',OH = J5',4' = 5.3, H-5'); 3.78 (td, 1 H, J4',5' = 5.3, J4',3' = 4.3, H-4'); 4.13 (ddd, 1 H, J3',2' = 5.0, J3',OH = 4.7, J3',4' = 4.3, H-3'); 4.18 (ddd, 1 H, J2',OH = 6.1, J2',1' = 5.3, J2',3' = 5.0, H-2'); 5.08 (t, 1 H, JOH,5' = 5.3, OH-5'); 5.50 (d, 1 H, JOH,2' = 6.1, OH-2'); 5.51 (d, 1 H, JOH,3' = 4.7, OH-3'); 6.60 (d, 1 H, J1',2' = 5.3, H-1'); 7.02 (d, 1 H, J5,6 = 3.8, H-5); 7.25 (bs, 1 H, H-4-furyl); 7.79 (d, 1 H, J6,5 = 3.8, H-6); 7.90 (bs, 1 H, H-5-furyl); 8.71 (bs, 1 H, H-2-furyl); 8.76 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 61.08 (CH2-5'); 75.23 (CH-3'); 76.19 (CH-2'); 83.33 (CH-1'); 83.86 (CH-4'); 99.65 (CH-5); 109.58 (CH-4-furyl); 114.25 (C-4a); 125.32 (C-3-furyl); 129.65 (CH-6); 144.73 (CH-5-furyl); 144.87 (CH-2-furyl); 149.70 (C-4); 150.88 (CH-2); 151.42 (C-7a). MS (ESI) m/z: 318 [M + H]. HRMS (ESI) for C15H16O5N3[M + H] calculated: 318.10845; found: 318.10838. For C15H15O5N3 calculated: 56.7% C, 4.76% H, 13.24% N; found: 56.28% C, 4.7% H, 12.82% N. 4-(Thiophene-3-yl)-7-(ß-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (21e) Compound 21e was prepared as described for compound 21d from compound 19 (155 mg, 0.54 mmol) and 3-thienylboronic acid. Compound 21e (123 mg, 68%) was obtained as an off-white crystalline solid after recrystallization (H2O-MeOH, 2:1). M.p. 215-217 °C. [a]D 20 -9.5 (c 0.211, DMSO). IR (ATR): 3520, 1578, 1461, 1248, 1076, 1026 cm-1. 1H NMR (499.8 MHz, DMSO-d6): 3.65 (ddd, 1 H, Jgem = 11.7, J5'b,OH = 5.4, J5'b,4' = 4.8, H-5'b); 3.72 (ddd, 1 H, Jgem = 11.7, J5'a,OH = 5.4, J5'a,4' = 4.2, H-5'a); 3.79 (ddd, 1 H, J4',3' = 5.0, J4',5' = 4.8, 4.2, H-4'); 4.13 (dt, 1 H, J3',4' = 5.0, J3',OH = 4.4, J3',2' = 4.2, H-3'); 4.18 (ddd, 1 H, J2',OH = 5.9, J2',1' = 5.1, J2',3' = 4.2, H-2'); 5.08 (t, 1 H, JOH,5' = 5.4, OH-5'); 5.516 (d, 1 H, JOH,2' = 5.9, OH-2'); 5.518 (d, 1 H, JOH,3' = 4.4, OH-3'); 6.62 (d, 1 H, J1',2' = 5.1, H-1'); 7.07 (d, 1 H, J5,6 = 3.8, H-5); 7.74 (dd, 1 H, J5,4 = 5.0, J5,2 = 2.9, H-5-thienyl); 7.83 (d, 1 H, J6,5 = 3.8, H-6); 7.95 (dd, 1 H, J4,5 = 5.0, J4,2 = 1.2, H-4-thienyl); 8.53 (dd, 1 H, J2,5 = 2.9, J2,4 = 1.2, H-2-thienyl); 8.79 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 61.10 (CH2-5'); 75.28 (CH-3'); 76.18 (CH-2'); 83.37 (CH-1'); 83.89 (CH-4'); 99.87 (CH-5); 114.27 (C-4a); 127.27 (CH-5-thienyl); 127.59 (CH-4-thienyl); 128.47 (CH-2-thienyl); 129.99 (CH-6); 140.23 (C-3-thienyl); 150.83 (CH-2); 151.17 (C-4); 151.85 (C-7a). MS (ESI) m/z: 334 [M + H]. HRMS (ESI) for C15H16O4N3S [M + H] calculated: 334.0856; found: 334.0856. For C15H15O4N3S calculated: 54.04% C, 4.54% H, 12.60% N; found: 54.05% C, 4.51% H, 12.42% N. 4-Chloro-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-ß-D-arabinofuranosyl)- 7H-pyrrolo[2,3-d]pyrimidine (23) A mixture of powdered KOH (840 mg, 85%, 12.75 mmol), TDA-1 (0.26 ml, 0.81 mmol) in dry MeCN (40 ml) was stirred at r.t. for 10 min before 6-chloro-7-deazapurine 8 (768 mg, 5 mmol) was added. Stirring was continued for another 15 min and then 2-deoxy-2-fluoro-3,5-di-O-benzoyl-ß-D-arabinofuranosyl bromide 25 26 (2.12 g, 5 mmol, prepared from 26) in MeCN (40 ml) was added and the mixture was stirred at r.t. for 10 min. The mixture was neutralized by the addition of AcOH, evaporated to dryness and the residue was coevaporated with silica. Column chromatography (hexanes-AcOEt, 6:1) afforded chloro nucleoside 23 (1.79 g, 72%) as a colorless solid. Analytical data of compound 23 are as described23. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-phenyl- 7H-pyrrolo[2,3-d]pyrimidine (27a) An argon purged mixture of 4-chloro-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-ß-D-arabinofuranosyl)- 7H-pyrrolo[2,3-d]pyrimidine 23 (414 mg, 0.83 mmol), phenylboronic acid (153 mg, 1.25 mmol), K2CO3 (230 mg, 1.67 mmol) and Pd(PPh3)4 (48 mg, 0.04 mmol) in toluene (5 ml) was stirred at 100 °C for 3 h. After cooling the solids were filtered off and the filtrate was co-evaporated with silica and chromatography on silica (hexanes-AcOEt, 6:1) afforded product 27a (426 mg, 95%) as a colorless foam. 1H NMR (400.1 MHz, CDCl3): 4.59 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 2.9, H-4'); 4.82 (m, 2 H, H-5'a and 5'b); 5.38 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.9, J2',3' = 0.9, H-2'); 5.78 (ddd, 1 H, JH,F = 17.3, J3',4' = 3.0, J3',2' = 0.8, H-3'); 6.89 (d, 1 H, J5,6 = 3.9, H-5); 6.99 (dd, 1 H, JH,F = 23.2, J1',2' = 2.8, H-1'); 7.43-7.69 (m, 10 H, H-m-Bz, H-6, H-p-Bz); 8.09-8.16 (m, 6 H, H-o-Bz); 8.98 (s, 1 H, H-2). MS (ESI) m/z: 538 (M + H), 560 (M + Na). HRMS (ESI) for C31H25N3O5F [M + H] calculated: 538.1773; found 538.1771. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(furan-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (27b) An argon purged mixture of compound 23 (496 mg, 1 mmol), 2-(tributylstannyl)furane (411 µl, 1.30 mmol) and PdCl2(PPh3)2 (35 mg, 0.05 mmol) in DMF (5 ml) was stirred at 100 °C for 1 h. After cooling volatiles were removed in vacuo and the residue was several times co-evaporated with toluene. Column chromatography on silica (hexanes-AcOEt, 20:1[arrow right]6:1) afforded product 27b (511 mg, 97%) as a colorless foam. 1H NMR (400.1 MHz, CDCl3): 4.57 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 2.9, H-4'); 4.81 (m, 2 H, H-5'a and 5'b); 5.36 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.8, J2',3' = 0.9, H-2'); 5.76 (ddd, 1 H, JH,F = 17.2, J3',4' = 2.9, J3',2' = 0.8, H-3'); 6.63 (dd, 1 H, J4,3 = 3.5, J4,5 = 1.8, H-4-furyl); 6.94 (dd, 1 H, JH,F = 23.2, J1',2' = 2.8, H-1'); 7.08 (d, 1 H, J5,6 = 3.9, H-5); 7.42-7.67 (m, 8 H, H-m-Bz, H-6, H-3-furyl, H-p-Bz); 7.71 (dd, 1 H, J5,4 = 1.8, J5,3 = 0.8, H-5-furyl); 8.11 (m, 4 H, H-o-Bz); 8.86 (s, 1 H, H-2). MS (ESI) m/z: 528 (M + H), 550 (M + Na). HRMS (ESI) for C29H23N3O6F [M + H] calculated: 528.1565; found 528.1562. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(thiophen-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (27c) Compound 27c was prepared as described for 27b by the reaction of compound 23 (496 mg, 1 mmol) and 2-(tributylstannyl)thiophene. Yield 495 mg (91%). Colorless foam. 1H NMR (400.1 MHz, CDCl3): 4.58 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 2.9, H-4'); 4.81 (m, 2 H, H-5'a and 5'b); 5.37 (ddd, 1 H, JH,F = 50.0, J2',1' = 2.8, J2',3' = 0.9, H-2'); 5.77 (ddd, 1 H, JH,F = 17.2, J3',4' = 2.9, J3',2' = 0.9, H-3'); 6.94 (d, 1 H, J5,6 = 3.9, H-5); 6.96 (dd, 1 H, JH,F = 23.2, J1',2' = 2.8, H-1'); 7.23 (dd, 1 H, J4,5 = 5.1, J4,3 = 3.8, H-4-thienyl); 7.46, 7.51 (2 × m, 2 × 2 H, H-m-Bz); 7.55-7.61 (m, 1 H, H-6); 7.57 (dd, 1 H, J5,4 = 5.2, J5,3 = 1.2, H-5-thienyl); 7.62, 7.65 (2 × m, 2 × 1 H, H-p-Bz); 7.98 (dd, 1 H, J3,4 = 3.8, J3,5 = 1.2, H-3-thienyl); 8.11 (m, 4 H, H-o-Bz); 8.86 (s, 1 H, H-2). MS (ESI) m/z: 544 (M + H), 566 (M + Na). HRMS (ESI) for C29H23N3O5FS [M + H] calculated: 544.1337; found 544.1334. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(furan-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (27d) Compound 27d was prepared as described for 27a by the reaction of compound 23 (372 mg, 0.75 mmol) and furane-3-boronic acid. Yield 384 mg (97%). Colorless foam. 1H NMR (400.1 MHz, CDCl3): 4.58 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 2.9, H-4'); 4.81 (m, 2 H, H-5'a and 5'b); 5.37 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.8, J2',3' = 0.8, H-2'); 5.76 (ddd, 1 H, JH,F = 17.2, J3',4' = 3.0, J3',2' = 0.8, H-3'); 6.75 (d, 1 H, J5,6 = 3.9, H-5); 6.95 (dd, 1 H, JH,F = 23.2, J1',2' = 2.8, H-1'); 7.14 (dd, 1 H, J4,5 = 1.9, J4,2 = 0.9, H-4-furyl); 7.41-7.68 (m, 8 H, H-m-Bz, H-6, H-5-furyl, H-p-Bz); 8.27 (dd, 1 H, J2,5 = 1.5, J2,4 = 0.9, H-2-furyl); 8.08-8.14 (m, 4 H, H-o-Bz); 8.87 (s, 1 H, H-2). MS (ESI) m/z: 528 (M + H), 550 (M + Na). HRMS (ESI) for C29H23N3O6F [M + H] calculated: 528.1565; found 528.1564. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(thiophen-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (27e) Compound 27e was prepared as described for 27a by the reaction of compound 23 (621 mg, 1.25 mmol) and thiophene-3-boronic acid. Yield 645 mg (95%). Colorless foam. 1H NMR (400.1 MHz, CDCl3): 4.58 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 3.0, H-4'); 4.81 (m, 2 H, H-5'a and 5'b); 5.37 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.8, J2',3' = 0.9, H-2'); 5.77 (ddd, 1 H, JH,F = 17.2, J3',4' = 2.9, J3',2' = 0.9, H-3'); 6.88 (d, 1 H, J5,6 = 3.9, H-5); 6.97 (dd, 1 H, JH,F = 23.2, J1',2' = 2.8, H-1'); 7.43-7.69 (m, 8 H, H-m-Bz, H-6, H-5-thienyl, H-p-Bz); 7.89 (dd, 1 H, J4,5 = 5.1, J4,2 = 1.3, H-4-thienyl); 8.09-8.16 (m, 4 H, H-o-Bz); 8.20 (dd, 1 H, J2,5 = 3.0, J2,4 = 1.3, H-2-thienyl); 8.91 (s, 1 H, H-2). MS (ESI) m/z: 544 (M + H), 566 (M + Na). HRMS (ESI) for C29H23N3O5FS [M + H] calculated: 544.1337; found 544.1334. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(thiazol-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (27g) Compound 27g was prepared as described for 27b by the reaction of compound 23 (337 mg, 0.68 mmol) and 2-(tributylstannyl)thiazole. Reaction time 18 h. Yield 300 mg (81%). Yellowish oil. 1H NMR (400.1 MHz, CDCl3): 4.59 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 3.0, H-4'); 4.82 (m, 2 H, H-5'a and 5'b); 5.37 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.9, J2',3' = 0.9, H-2'); 5.77 (ddd, 1 H, JH,F = 17.2, J3',4' = 3.0, J3',2' = 0.9, H-3'); 6.97 (dd, 1 H, JH,F = 23.0, J1',2' = 2.9, H-1'); 7.43-7.70 (m, 9 H, H-5-thiazolyl, H-5, H-m-Bz, H-6, H-p-Bz); 8.09-8.15 (m, 5 H, H-4-thiazolyl, H-o-Bz); 8.91 (s, 1 H, H-2). MS (ESI) m/z: 545 (M + H), 567 (M + Na). 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-methyl- 7H-pyrrolo[2,3-d]pyrimidine (27h) An argon purged mixture of compound 23 (337 mg, 0.68 mmol), trimethylaluminium (2 M in toluene, 680 µl, 1.36 mmol) and Pd(PPh3)4 (39 mg, 0.034 mmol) in THF (3 ml) was stirred at 100 °C for 6 h. The mixture was diluted with CHCl3 (20 ml) and treated with aq. NH4Cl (sat., 20 ml). The slurry was filtered through cellite and after phase separation, aqueous phase was re-extracted with CHCl3 (2 × 10 ml). Combined organics were dried over MgSO4, evaporated and the residue was chromatographed on silica (hexanes-AcOEt, 2:1) affording compound 27h (320 mg, 99%) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): 2.76 (s, 3 H, CH3); 4.56 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 3.0, H-4'); 4.79 (m, 2 H, H-5'a and 5'b); 5.34 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.8, J2',3' = 1.0, H-2'); 5.76 (ddd, 1 H, JH,F = 17.3, J3',4' = 2.9, J3',2' = 1.0, H-3'); 6.62 (d, 1 H, J5,6 = 3.8, H-5); 6.91 (dd, 1 H, JH,F = 23.2, J1',2' = 2.9, H-1'); 7.45 (m, 2 H, H-m-Bz); 7.48-7.55 (m, 3 H, H-m-Bz and H-6); 7.58, 7.66 (2 × m, 2 × 1 H, H-p-Bz); 8.11 (m, 4 H, H-o-Bz); 8.78 (s, 1 H, H-2). MS (ESI) m/z: 476 (M + H). HRMS (ESI) for C26H23N3O5F [M + H] calculated: 476.1616; found 476.1607. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-phenyl- 7H-pyrrolo[2,3-d]pyrimidine (28a) Compound 27a (400 mg, 0.74 mmol) was treated with NaOMe (1 M in MeOH, 200 µl, 0.2 mmol) in MeOH (5 ml) for 12 h at r.t.. The mixture was co-evaporated with silica and chromatographed on a column of silica (2.5% MeOH in CHCl3) affording product 28a (225 mg, 92%) as a colorless foamy solid. M.p. 72-76 °C. [a]D +44.2 (c 0.339, DMSO). 11H NMR (400.1 MHz, DMSO-d6): 3.66 (dtd, 1 H, Jgem = 11.9, J5'b,OH = J5'b,4' = 5.7, JH,F = 0.9, H-5'b); 3.725 (dddd, 1 H, Jgem = 11.9, J5'a,OH = 5.7, J5'a,4' = 4.3, JH,F = 1.4, H-5'a); 3.88 (dddd, 1 H, J4',5' = 5.7, 4.3, J4',3' = 5.1, JH,F = 0.5, H-4'); 4.45 (dtd, 1 H, JH,F = 19.0, J3',4' = J3',OH = 5.1, J3',2' = 3.8, H-3'); 5.13 (t, 1 H, JOH,5' = 5.7, OH-5'); 5.24 (ddd, 1 H, JH,F = 52.7, J2',1' = 4.6, J2',3' = 3.8, H-2'); 5.99 (d, 1 H, JOH,3' = 5.0, OH-3'); 6.80 (dd, 1 H, JH,F = 15.1, J1',2' = 4.6, H-1'); 7.02 (d, 1 H, J5,6 = 3.8, H-5); 7.54-7.63 (m, 3 H, H-m,p-Ph); 7.85 (dd, 1 H, J6,5 = 3.8, JH,F = 2.2, H-6); 8.17 (m, 2 H, H-o-Ph); 8.92 (s, 1 H, H-2). 13C NMR (100.6 MHz, DMSO-d6): 60.62 (CH2-5'); 73.07 (d, JC,F = 23.3, CH-3'); 81.40 (d, JC,F = 16.8, CH-1'); 83.41 (d, JC,F = 5.0, CH-4'); 96.02 (d, JC,F = 191.7, CH-2'); 101.05 (CH-5); 115.13 (C-4a); 128.78 (CH-o-Ph); 129.05 (CH-m-Ph); 129.09 (d, JC,F = 3.9, CH-6); 130.45 (CH-p-Ph); 137.56 (C-i-Ph); 151.30 (CH-2); 151.72 (C-7a); 156.31 (C-4). 19F NMR (470.3 MHz, DMSO-d6): -197.90. MS (ESI) m/z: 330 (M + H), 352 (M + Na). HRMS (ESI) for C17H17N3O3F [M + H] calculated: 330.1249; found: 330.1248. HRMS (ESI) for C17H16N3O3FNa [M + Na] calculated: 352.1068; found: 352.1067. For C17H16N3O3F.0.3H2O calculated: 61.00% C, 5.00% H, 12.55% N; found: 61.28% C, 4.97% H, 12.28% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(furan-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (28b). Deprotection of 27b (495 mg, 0.94 mmol) as described for 28a gave compound 28b as a beige foam. Yield 270 mg (90%). Compound 28b crystallized from MeOH(trace)-AcOEt- hexanes as a beige microcrystalline solid. M.p. 185-187 °C. [a]D +39.9 (c 0.321, DMSO). 1H NMR (600.1 MHz, DMSO-d6): 3.65 (dddd, 1 H, Jgem = 11.8, J5'b,OH = 5.7, J5'b,4' = 5.3, JH,F = 0.9, H-5'b); 3.71 (dddd, 1 H, Jgem = 11.8, J5'a,OH = 5.7, J5'a,4' = 4.3, JH,F = 1.6, H-5'a); 3.86 (tdd, 1 H, J4',5' = 5.3, 4.3, J4',3' = 5.3, JH,F = 0.8, H-4'); 4.42 (dddd, 1 H, JH,F = 19.0, J3',4' = 5.3, J3',OH = 5.0, J3',2' = 3.7, H-3'); 5.13 (t, 1 H, JOH,5' = 5.7, OH-5'); 5.22 (ddd, 1 H, JH,F = 52.6, J2',1' = 4.6, J2',3' = 3.7, H-2'); 5.98 (d, 1 H, JOH,3' = 5.0, OH-3'); 6.74 (dd, 1 H, JH,F = 15.2, J1',2' = 4.6, H-1'); 6.79 (dd, 1 H, J4,3 = 3.5, J4,5 = 1.8, H-4-furyl); 7.07 (d, 1 H, J5,6 = 3.8, H-5); 7.49 (dd, 1 H, J3,4 = 3.5, J3,5 = 0.8, H-3-furyl); 7.81 (dd, 1 H, J6,5 = 3.8, JH,F = 2.3, H-6); 8.07 (dd, 1 H, J5,4 = 1.8, J5,3 = 0.8, H-5-furyl); 8.79 (s, 1 H, H-2). 13C NMR (150.9 MHz, DMSO-d6): 60.63 (CH2-5'); 73.01 (d, JC,F = 23.2, CH-3'); 81.22 (d, JC,F = 16.8, CH-1'); 83.35 (d, JC,F = 5.2, CH-4'); 96.05 (d, JC,F = 191.6, CH-2'); 101.41 (CH-5); 112.34 (C-4a); 112.92 (CH-4-furyl); 113.60 (CH-3-furyl); 129.16 (d, JC,F = 3.6, CH-6); 146.62 (C-4); 146.64 (CH-5-furyl); 151.37 (CH-2); 151.86 (C-7a); 152.59 (C-2-furyl). 19F NMR (470.3 MHz, DMSO-d6): -194.35. MS (ESI) m/z: 320 (M + H), 342 (M + Na). HRMS (ESI) for C15H15N3O4F [M + H] calculated: 320.1041; found: 320.1041. HRMS (ESI) for C15H14N3O4FNa [M + Na] calculated: 342.0861; found: 342.0860. For C15H14N3O4F calculated: 56.43% C, 4.42%% H, 13.16% N; found: 56.12% C, 4.53% H, 12.87% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(thiophen-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (28c) Deprotection of 27c (470 mg, 0.86 mmol) as described for 28a gave compound 28c as an amorphous yellow solid. Yield 247 mg (85%). Compound 28c was recrystallized from EtOH as an yellow crystalline solid. M.p. 144-146 °C. [a]D +39.8 (c 0.587, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 3.66 (dddd, 1 H, Jgem = 11.8, J5'b,OH = 5.7, J5'b,4' = 5.3, JH,F = 0.8, H-5'b); 3.72 (dddd, 1 H, Jgem = 11.8, J5'a,OH = 5.7, J5'a,4' = 4.3, JH,F = 1.6, H-5'a); 3.86 (tdd, 1 H, J4',5' = 5.3, 4.3, J4',3' = 5.3, JH,F = 0.7, H-4'); 4.44 (dddd, 1 H, JH,F = 19.0, J3',4' = 5.3, J3',OH = 5.0, J3',2' = 3.9, H-3'); 5.15 (t, 1 H, JOH,5' = 5.7, OH-5'); 5.23 (ddd, 1 H, JH,F = 52.8, J2',1' = 4.6, J2',3' = 3.9, H-2'); 5.99 (d, 1 H, JOH,3' = 5.0, OH-3'); 6.75 (dd, 1 H, JH,F = 14.5, J1',2' = 4.6, H-1'); 7.19 (d, 1 H, J5,6 = 3.9, H-5); 7.31 (dd, 1 H, J4,5 = 5.1, J4,3 = 3.8, H-4-thienyl); 7.85 (dd, 1 H, J6,5 = 3.9, JH,F = 2.3, H-6); 7.87 (dd, 1 H, J5,4 = 5.1, J5,3 = 1.1, H-5-thienyl); 8.18 (dd, 1 H, J3,4 = 3.8, J3,5 = 1.1, H-3-thienyl); 8.78 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.58 (CH2-5'); 72.91 (d, JC,F = 23.2, CH-3'); 81.30 (d, JC,F = 16.8, CH-1'); 83.31 (d, JC,F = 5.4, CH-4'); 96.06 (d, JC,F = 191.7, CH-2'); 101.04 (CH-5); 112.68 (C-4a); 129.32 (d, JC,F = 3.6, CH-6); 129.35 (CH-4-thienyl); 129.91 (CH-3-thienyl); 131.08 (CH-5-thienyl); 142.50 (C-2-thienyl); 150.34 (C-4); 151.15 (CH-2); 151.79 (C-7a). 19F NMR (470.3 MHz, DMSO-d6): -194.43. MS (ESI) m/z: 336 (M + H), 358 (M + Na). HRMS (ESI) for C15H15N3O3FS [M + H] calculated: 336.0813; found: 336.0813. HRMS (ESI) for C15H14N3O3FSNa [M + Na] calculated: 358.0632; found: 358.0632. For C15H14N3O3FS calculated: 53.72% C, 4.21% H, 12.53% N; found: 53.47% C, 4.38% H, 12.24% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(furan-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (28d) Deprotection of 27d (370 mg, 0.70 mmol) as described for 28a gave compound 28d as a white foam. Yield 193 mg (86%). Compound 28d crystallized from MeOH-water as white leaves. M.p. 112-114 °C. [a]D +38.7 (c 0.336, DMSO). 1H NMR (400.1 MHz, DMSO-d6): 3.66 (dt, 1 H, Jgem = 12.0, J5'b,OH = J5'b,4' = 5.6, H-5'b); 3.72 (dddd, 1 H, Jgem = 12.0, J5'a,OH = 5.6, J5'a,4' = 4.3, JH,F = 1.5, H-5'a); 3.87 (ddd, 1 H, J4',5' = 5.6, 4.3, J4',3' = 5.3, H-4'); 4.44 (dddd, 1 H, JH,F = 19.2, J3',4' = 5.3, J3',OH = 5.0, J3',2' = 3.9, H-3'); 5.12 (t, 1 H, JOH,5' = 5.6, OH-5'); 5.22 (ddd, 1 H, JH,F = 52.7, J2',1' = 4.6, J2',3' = 3.9, H-2'); 5.97 (d, 1 H, JOH,3' = 5.0, OH-3'); 6.75 (dd, 1 H, JH,F = 14.7, J1',2' = 4.6, H-1'); 7.11 (d, 1 H, J5,6 = 3.8, H-5); 7.26 (dd, 1 H, J4,5 = 1.9, J4,2 = 0.8, H-4-furyl); 7.80 (dd, 1 H, J6,5 = 3.8, JH,F = 2.2, H-6); 7.90 (dd, 1 H, J5,4 = 1.9, J5,2 = 1.4, H-5-furyl); 8.74 (dd, 1 H, J2,5 = 1.4, J2,4 = 0.8, H-2-furyl); 8.81 (s, 1 H, H-2). 13C NMR (100.6 MHz, DMSO-d6): 60.59 (CH2-5'); 73.00 (d, JC,F = 23.3, CH-3'); 81.26 (d, JC,F = 16.9, CH-1'); 83.31 (d, JC,F = 5.1, CH-4'); 96.02 (d, JC,F = 191.7, CH-2'); 100.84 (CH-5); 109.51 (CH-4-furyl); 114.16 (C-4a); 125.11 (C-3-furyl); 128.58 (d, JC,F = 3.6, CH-6); 144.73 (CH-5-furyl); 145.02 (CH-2-furyl); 150.21 (C-4); 151.26 (CH-2); 151.32 (C-7a). 19F NMR (470.3 MHz, DMSO-d6): -198.01. MS (ESI) m/z: 320 (M + H), 342 (M + Na). HRMS (ESI) for C15H15N3O4F [M + H] calculated: 320.1041; found: 320.1041. HRMS (ESI) for C15H14N3O4FNa [M + Na] calculated: 342.0861; found: 342.0860. For C15H14N3O4F.0.5H2O calculated: 54.88% C, 4.61% H, 12.80% N; found: 55.10% C, 4.61% H, 12.48% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(thiophen-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (28e) Deprotection of 27e (620 mg, 1.14 mmol) as described for 28a gave compound 28e as a brownish foamy solid after evaporation from MeOH. Yield 340 mg (89%). M.p. 71-73 °C. [a]D +41.6 (c 0.375, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 3.66 (ddd, 1 H, Jgem = 12.0, J5'b,4' = 5.1, JH,F = 0.8, H-5'b); 3.72 (ddd, 1 H, Jgem = 12.0, J5'a,4' = 4.3, JH,F = 1.5, H-5'a); 3.87 (dddd, 1 H, J4',3' = 5.4, J4',5' = 5.1, 4.3, JH,F = 0.8, H-4'); 4.44 (ddd, 1 H, JH,F = 19.1, J3',4' = 5.4, J3',2' = 3.8, H-3'); 5.10 (bs, 1 H, OH-5'); 5.22 (ddd, 1 H, JH,F = 52.7, J2',1' = 4.6, J2',3' = 3.8, H-2'); 5.98 (bs, 1 H, OH-3'); 6.77 (dd, 1 H, JH,F = 14.9, J1',2' = 4.6, H-1'); 7.15 (dd, 1 H, J5,6 = 3.9, JH,F = 0.3, H-5); 7.75 (dd, 1 H, J5,4 = 5.0, J5,2 = 2.9, H-5-thienyl); 7.83 (dd, 1 H, J6,5 = 3.9, JH,F = 2.2, H-6); 7.96 (dd, 1 H, J4,5 = 5.0, J4,2 = 1.3, H-4-thienyl); 8.55 (dd, 1 H, J2,5 = 2.9, J2,4 = 1.3, H-2-thienyl); 8.84 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.63 (CH2-5'); 73.01 (d, JC,F = 23.1, CH-3'); 81.32 (d, JC,F = 16.9, CH-1'); 83.34 (d, JC,F = 5.2, CH-4'); 96.07 (d, JC,F = 191.7, CH-2'); 101.20 (CH-5); 114.24 (C-4a); 127.42 (CH-5-thienyl); 127.62 (CH-4-thienyl); 128.91 (CH-2-thienyl); 129.02 (d, JC,F = 3.5, CH-6); 139.93 (C-3-thienyl); 151.25 (CH-2); 151.65 (C-4); 151.80 (C-7a). 19F NMR (470.3 MHz, DMSO-d6): -197.97. MS (ESI) m/z: 336 (M + H), 358 (M + Na). HRMS (ESI) for C15H15N3O3FS [M + H] calculated: 336.0813; found: 336.0813. HRMS (ESI) for C15H14N3O3FSNa [M + Na] calculated: 358.0632; found: 358.0632. For C15H14N3O3FS calculated: 53.72% C, 4.21% H, 12.53% N; found: 53.61% C, 4.47% H, 12.15% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(thiazol-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (28g) Deprotection of 27g (290 mg, 0.53 mmol) as described for 28a gave compound 28g as a yellowish foamy solid after evaporation from diethylether. Yield 123 mg (69%). M.p. 150-152 °C. [a]D +39.5 (c 0.324, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 3.66 (dd, 1 H, Jgem = 11.9, J5'b,4' = 5.1, H-5'b); 3.72 (ddd, 1 H, Jgem = 11.9, J5'a,4' = 4.1, JH,F = 1.3, H-5'a); 3.87 (dddd, 1 H, J4',3' = 5.6, J4',5' = 5.1, 4.1, JH,F = 0.8, H-4'); 4.43 (dddd, 1 H, JH,F = 18.7, J3',4' = 5.6, J3',OH = 4.4, J3',2' = 3.8, H-3'); 5.13 (bs, 1 H, OH-5'); 5.24 (ddd, 1 H, JH,F = 52.7, J2',1' = 4.6, J2',3' = 3.8, H-2'); 5.99 (bd, 1 H, JOH,3' = 4.4, OH-3'); 6.77 (dd, 1 H, JH,F = 14.9, J1',2' = 4.6, H-1'); 7.31 (dd, 1 H, J5,6 = 3.7, JH,F = 0.4, H-5); 7.91 (dd, 1 H, J6,5 = 3.7, JH,F = 2.2, H-6); 8.05 (d, 1 H, J5,4 = 3.1, H-5-thiazolyl); 8.21 (d, 1 H, J4,5 = 3.1, H-4-thiazolyl); 8.90 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.61 (CH2-5'); 72.98 (d, JC,F = 23.2, CH-3'); 81.38 (d, JC,F = 16.8, CH-1'); 83.41 (d, JC,F = 5.3, CH-4'); 96.07 (d, JC,F = 191.7, CH-2'); 102.16 (CH-5); 113.41 (C-4a); 124.31 (CH-5-thiazolyl); 130.73 (d, JC,F = 3.6, CH-6); 145.78 (CH-4-thiazolyl); 148.27 (C-4); 151.19 (CH-2); 152.41 (C-7a); 167.33 (C-2-thiazolyl). 19F NMR (470.3 MHz, DMSO-d6): -197.98. MS (ESI) m/z: 337 (M + H), 359 (M + Na). HRMS (ESI) for C14H14N4O3FS [M + H] calculated: 337.0765; found: 337.0765. HRMS (ESI) for C14H13N4O3FSNa [M + Na] calculated: 359.0585; found: 359.0584. For C14H13N4O3FS.0.45C4H10O calculated: 51.33% C, 4.77% H, 15.15% N; found: 51.59% C, 4.53% H, 15.06% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-4-(methyl)- 7H-pyrrolo[2,3-d]pyrimidine (28h) Deprotection of 27h (300 mg, 0.63 mmol) as described for 28a gave compound 28h as a white solid. Yield 143 mg (85%). Column chromatography (4% MeOH in CHCl3). Compound 28h was recrystallized from water as white prisms. M.p. 175-177 °C. [a]D +32.2 (c 0.317, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 2.66 (s, 3 H, CH3); 3.63 (ddd, 1 H, Jgem = 12.0, J5'b,OH = 5.7, J5'b,4' = 5.2, JH,F = 0.8, H-5'b); 3.69 (dddd, 1 H, Jgem = 12.0, J5'a,OH = 5.7, J5'a,4' = 4.3, JH,F = 1.5, H-5'a); 3.84 (dddd, 1 H, J4',5' = 5.2, 4.3, J4',3' = 5.0, JH,F = 0.9, H-4'); 4.40 (dtd, 1 H, JH,F = 19.1, J3',4' = J3',OH = 5.0, J3',2' = 3.8, H-3'); 5.08 (t, 1 H, JOH,5' = 5.7, OH-5'); 5.18 (ddd, 1 H, JH,F = 52.7, J2',1' = 4.6, J2',3' = 3.8, H-2'); 5.93 (d, 1 H, JOH,3' = 5.0, OH-3'); 6.69 (dd, 1 H, JH,F = 15.0, J1',2' = 4.6, H-1'); 6.76 (dd, 1 H, J5,6 = 3.8, JH,F = 0.4, H-5); 7.67 (dd, 1 H, J6,5 = 3.8, JH,F = 2.2, H-6); 8.67 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 21.33 (CH3); 60.62 (CH2-5'); 72.98 (d, JC,F = 23.2, CH-3'); 81.20 (d, JC,F = 16.9, CH-1'); 83.21 (d, JC,F = 5.3, CH-4'); 96.02 (d, JC,F = 191.7, CH-2'); 100.29 (CH-5); 117.58 (C-4a); 127.46 (d, JC,F = 3.6, CH-6); 150.09 (C-7a); 151.11 (CH-2); 159.21 (C-4). 19F NMR (470.3 MHz, DMSO-d6): -198.03. MS (ESI) m/z: 268 (M + H), 290 (M + Na). HRMS (ESI) for C12H15N3O3F [M + H] calculated: 268.1092; found: 268.1092. HRMS (ESI) for C12H14N3O3FNa [M + Na] calculated: 290.0911; found: 290.0912. For C12H14N3O3F calculated: 53.93% C, 5.28% H, 15.72% N; found: 53.87% C, 5.25% H, 15.63% N. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(furan-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (29b) Compound 29b was prepared as described for 27b by the reaction of compound 24 (514 mg, 1 mmol) and 2-(tributylstannyl)furane. Yield 480 mg (88%). Yellowish oil. 1H NMR (400.1 MHz, CDCl3): 4.56 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 2.9, H-4'); 4.79 (m, 2 H, H-5'a and 5'b); 5.35 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.9, J2',3' = 0.9, H-2'); 5.74 (ddd, 1 H, JH,F = 17.3, J3',4' = 2.9, J3',2' = 0.9, H-3'); 6.65 (dd, 1 H, J4,3 = 3.6, J4,5 = 1.7, H-4-furyl); 6.99 (ddd, 1 H, JH,F = 22.8, 1.7, J1',2' = 2.9, H-1'); 7.39 (dd, 1 H, JH,F = 2.8, 2.3, H-6); 7.43-7.70 (m, 7 H, H-m-Bz, H-3-furyl, H-p-Bz); 7.74 (dd, 1 H, J5,4 = 1.8, J5,3 = 0.8, H-5-furyl); 8.11 (m, 4 H, H-o-Bz); 8.88 (s, 1 H, H-2). MS (ESI) m/z: 546 (M + H), 568 (M + Na). HRMS (ESI) for C29H22N3O6F2 [M + H] calculated: 546.1471; found: 546.1468. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(thiophen-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (29c) Compound 29c was prepared as described for 27b by the reaction of compound 24 (514 mg, 1 mmol) and 2-(tributylstannyl)thiophene. Yield 500 mg (89%). Yellowish oil. 1H NMR (400.1 MHz, CDCl3): 4.56 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 3.0, H-4'); 4.80 (m, 2 H, H-5'a and 5'b); 5.35 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.9, J2',3' = 0.8, H-2'); 5.74 (ddd, 1 H, JH,F = 17.2, J3',4' = 2.9, J3',2' = 0.7, H-3'); 6.99 (ddd, 1 H, JH,F = 23.2, 1.8, J1',2' = 2.8, H-1'); 7.23 (dd, 1 H, J4,5 = 5.1, J4,3 = 3.9, H-4-thienyl); 7.39 (dd, 1 H, JH,F = 3.0, 2.2, H-6); 7.43-7.69 (m, 7 H, H-m-Bz, H-5-thienyl, H-p-Bz); 8.12 (m, 4 H, H-o-Bz); 8.17 (dd, 1 H, J3,4 = 3.9, J3,5 = 1.1, H-3-thienyl); 8.81 (s, 1 H, H-2). MS (ESI) m/z: 562 (M + H), 584 (M + Na). HRMS (ESI) for C29H22N3O5F2S [M + H] calculated: 562.1243; found: 562.1240. HRMS (ESI) for C29H21N3O5F2SNa [M + Na] calculated: 584.1062; found: 584.1060. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(furan-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (29d) Compound 29d was prepared as described for 27a by the reaction of compound 24 (514 mg, 1 mmol) and furane-3-boronic acid. Yield 496 mg (91%). Colorless foam. 1H NMR (400.1 MHz, CDCl3): 4.56 (dt, 1 H, J4',5' = 4.8, 4.8, J4',3' = 3.0, H-4'); 4.79 (m, 2 H, H-5'a and 5'b); 5.35 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.9, J2',3' = 0.8, H-2'); 5.74 (ddd, 1 H, JH,F = 17.4, J3',4' = 2.7, J3',2' = 0.7, H-3'); 6.99 (ddd, 1 H, JH,F = 23.2, 1.8, J1',2' = 2.8, H-1'); 7.25 (m, 1 H, H-4-furyl); 7.37 (t, 1 H, JH,F = 2.6, H-6); 7.42-7.70 (m, 7 H, H-m-Bz, H-5-furyl, H-p-Bz); 8.11 (m, 4 H, H-o-Bz); 8.41 (dd, 1 H, J2,5 = 1.5, J2,4 = 0.8, H-2-furyl); 8.86 (s, 1 H, H-2). MS (ESI) m/z: 546 (M + H), 568 (M + Na). HRMS (ESI) for C29H22N3O6F2 [M + H] calculated: 546.1471; found: 546.1467. 7-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(thiophen-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (29e) Compound 29e was prepared as described for 27a by the reaction of compound 24 (514 mg, 1 mmol) and thiophene-3-boronic acid. Yield 494 mg (88%). Yellowish foam. 1H NMR (400.1 MHz, CDCl3): 4.56 (dt, 1 H, J4',5' = 4.7, 4.7, J4',3' = 2.8, H-4'); 4.80 (m, 2 H, H-5'a and 5'b); 5.36 (ddd, 1 H, JH,F = 50.1, J2',1' = 2.9, J2',3' = 0.9, H-2'); 5.74 (ddd, 1 H, JH,F = 17.3, J3',4' = 3.0, J3',2' = 0.9, H-3'); 7.01 (ddd, 1 H, JH,F = 23.2, 2.0, J1',2' = 2.9, H-1'); 7.38 (dd, 1 H, JH,F = 3.0, 2.2, H-6); 7.42-7.69 (m, 7 H, H-m-Bz, H-5-thienyl, H-p-Bz); 7.93 (dd, 1 H, J4,5 = 5.1, J4,2 = 1.0, H-4-thienyl); 8.12 (m, 4 H, H-o-Bz); 8.30 (dd, 1 H, J2,5 = 3.0, J2,4 = 0.9, H-2-thienyl); 8.88 (s, 1 H, H-2). MS (ESI) m/z: 562 (M + H), 584 (M + Na). HRMS (ESI) for C29H22N3O5F2S [M + H] calculated: 562.1243; found: 562.1240. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(furan-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (30b) Deprotection of 29b (465 mg, 0.85 mmol) as described for 28a gave compound 30b as a yellowish oil which solidified on standing. Yield 270 mg (94%). Compound 30b was recrystallized from MeOH. M.p. 187-188 °C. [a]D +46.9 (c 0.460, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 3.64 (dddd, 1 H, Jgem = 12.0, J5'b,OH = 5.6, J5'b,4' = 4.7, JH,F = 0.6, H-5'b); 3.71 (dddd, 1 H, Jgem = 12.0, J5'a,OH = 5.6, J5'a,4' = 4.0, JH,F = 1.6, H-5'a); 3.85 (dddd, 1 H, J4',3' = 5.5, J4',5' = 4.7, 4.0, JH,F = 0.8, H-4'); 4.41 (ddd, 1 H, JH,F = 19.2, J3',4' = 5.5, J3',OH = 5.1, J3',2' = 4.3, H-3'); 5.13 (t, 1 H, JOH,5' = 5.6, OH-5'); 5.23 (ddd, 1 H, JH,F = 52.8, J2',1' = 4.7, J2',3' = 4.3, H-2'); 5.95 (t, 1 H, JOH,3' = 5.1, OH-3'); 6.80 (ddd, 1 H, JH,F = 13.3, 1.7, J1',2' = 4.7, H-1'); 6.81 (dd, 1 H, J4,3 = 3.5, J4,5 = 1.7, H-4-furyl); 7.49 (dd, 1 H, J3,4 = 3.5, J3,5 = 0.8, H-3-furyl); 7.85 (t, 1 H, JH,F = 1.9, H-6); 8.08 (dd, 1 H, J5,4 = 1.7, J5,3 = 0.8, H-5-furyl); 8.82 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.42 (CH2-5'); 72.51 (d, JC,F = 23.0, CH-3'); 80.75 (d, JC,F = 16.9, CH-1'); 83.17 (d, JC,F = 5.9, CH-4'); 95.98 (d, JC,F = 192.0, CH-2'); 101.90 (d, JC,F = 15.9, C-4a); 111.85 (dd, JC,F = 30.7, 3.4, CH-6); 113.13 (CH-4-furyl); 115.02 (d, JC,F = 5.8, CH-3-furyl); 141.33 (d, JC,F = 249.0, C-5); 146.06 (d, JC,F = 3.7, C-4); 147.08 (CH-5-furyl); 147.26 (d, JC,F = 3.1, C-7a); 150.99 (d, JC,F = 1.6, C-2-furyl); 151.88 (CH-2). 19F NMR (470.3 MHz, DMSO-d6): -198.80 (ddd, JF,H = 52.8, 19.2, 13.3); -161.19 (s). MS (ESI) m/z: 338 (M + H), 360 (M + Na). HRMS (ESI) for C15H14N3O4F2 [M + H] calculated: 338.0947; found: 338.0947. HRMS (ESI) for C15H13N3O4F2Na [M + Na] calculated: 360.0766; found: 360.0766. For C15H13N3O4F2 calculated: 53.42% C, 3.88% H, 12.46% N; found: 53.40% C, 4.12% H, 12.07% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(thiophen-2-yl)- 7H-pyrrolo[2,3-d]pyrimidine (30c) Deprotection of 29c (485 mg, 0.86 mmol) as described for 28a gave compound 30c as a yellow foamy solid. Yield 278 mg (91%). Compound 30c was crystallized from MeOH-water as off white needles. M.p. 104-106 °C. [a]D +43.8 (c 0.653, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 3.65 (ddd, 1 H, Jgem = 12.1, J5'b,4' = 5.0, JH,F = 0.7, H-5'b); 3.72 (ddd, 1 H, Jgem = 12.0, J5'a,4' = 4.1, JH,F = 1.6, H-5'a); 3.85 (dddd, 1 H, J4',3' = 5.7, J4',5' = 5.0, 4.1, JH,F = 0.9, H-4'); 4.42 (ddd, 1 H, JH,F = 19.1, J3',4' = 5.7, J3',2' = 4.2, H-3'); 5.24 (ddd, 1 H, JH,F = 52.8, J2',1' = 4.8, J2',3' = 4.2, H-2'); 6.80 (ddd, 1 H, JH,F = 13.2, 1.9, J1',2' = 4.8, H-1'); 7.305 (dd, 1 H, J4,5 = 5.0, J4,3 = 3.8, H-4-thienyl); 7.88 (t, 1 H, JH,F = 1.9, H-6); 7.89 (dd, 1 H, J5,4 = 5.0, J5,3 = 1.1, H-5-thienyl); 8.07 (dd, 1 H, J3,4 = 3.8, J3,5 = 1.1, H-3-thienyl); 8.78 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.48 (CH2-5'); 72.56 (d, JC,F = 23.0, CH-3'); 80.93 (d, JC,F = 16.9, CH-1'); 83.26 (d, JC,F = 5.9, CH-4'); 96.02 (d, JC,F = 192.1, CH-2'); 102.30 (d, JC,F = 15.4, C-4a); 111.84 (dd, JC,F = 31.7, 3.2, CH-6); 129.42 (d, JC,F = 2.4, CH-4-thienyl); 130.45 (d, JC,F = 16.2, CH-3-thienyl); 132.10 (CH-5-thienyl); 141.48 (d, JC,F = 246.1, C-5); 141.85 (d, JC,F = 1.4, C-2-thienyl); 147.25 (d, JC,F = 3.5, C-7a); 150.35 (d, JC,F = 3.9, C-4); 151.82 (CH-2). 19F NMR (470.3 MHz, DMSO-d6): -198.76 (ddd, JF,H = 52.8, 19.1, 13.2); -160.20 (s). MS (ESI) m/z: 354 (M + H), 376 (M + Na). HRMS (ESI) for C15H14N3O3F2S [M + H] calculated: 354.0718; found: 354.0718. HRMS (ESI) for C15H13N3O3F2SNa [M + Na] calculated: 376.0538; found: 376.0537. For C15H13N3O3F2S.0.2H2O.0.6CH4O calculated: 49.81% C, 4.23% H, 11.17% N; found: 49.90% C, 4.12% H, 11.05% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(furan-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (30d) Deprotection of 29d (480 mg, 0.88 mmol) as described for 28a gave compound 30d as a yellow foamy solid. Yield 276 mg (93%). Compound 30d was crystallized from MeOH- diethylether as a ochry solid. M.p. 77-79 °C. [a]D +32.8 (c 0.445, DMSO). 1H NMR (600.1 MHz, DMSO-d6): 3.65 (ddd, 1 H, Jgem = 12.0, J5'b,4' = 4.9, JH,F = 0.7, H-5'b); 3.71 (ddd, 1 H, Jgem = 12.0, J5'a,4' = 4.0, JH,F = 1.5, H-5'a); 3.84 (dddd, 1 H, J4',3' = 5.7, J4',5' = 4.9, 4.0, JH,F = 0.9, H-4'); 4.41 (ddd, 1 H, JH,F = 19.3, J3',4' = 5.7, J3',2' = 4.2, H-3'); 5.12 (bs, 1 H, OH-5'); 5.23 (ddd, 1 H, JH,F = 52.8, J2',1' = 4.8, J2',3' = 4.2, H-2'); 5.96 (bs, 1 H, OH-3'); 6.80 (ddd, 1 H, JH,F = 13.2, 1.9, J1',2' = 4.8, H-1'); 7.17 (dt, 1 H, J4,5 = 1.8, J4,2 = JH,F = 0.7, H-4-furyl); 7.83 (t, 1 H, JH,F = 1.9, H-6); 7.90 (dd, 1 H, J5,4 = 1.8, J5,2 = 1.5, H-5-furyl); 8.48 (dt, 1 H, J2,5 = 1.5, J2,4 = JH,F = 0.7, H-5-furyl); 8.84 (s, 1 H, H-2). 13C NMR (150.9 MHz, DMSO-d6): 60.45 (CH2-5'); 72.53 (d, JC,F = 23.0, CH-3'); 80.78 (d, JC,F = 16.9, CH-1'); 83.18 (d, JC,F = 5.9, CH-4'); 95.99 (d, JC,F = 192.1, CH-2'); 103.82 (d, JC,F = 15.6, C-4a); 109.91 (d, JC,F = 6.3, CH-4-furyl); 111.39 (dd, JC,F = 30.8, 3.2, CH-6); 124.42 (d, JC,F = 1.0, C-3-furyl); 141.42 (d, JC,F = 246.0, C-5); 144.90 (d, JC,F = 0.9, CH-5-furyl); 145.55 (d, JC,F = 13.3, CH-2-furyl); 146.92 (d, JC,F = 3.4, C-7a); 149.74 (d, JC,F = 3.7, C-4); 152.09 (CH-2). 19F NMR (470.3 MHz, DMSO-d6): -198.79 (ddd, JF,H = 52.8, 19.3, 13.2); -162.57 (s). MS (ESI) m/z: 338 (M + H), 360 (M + Na). HRMS (ESI) for C15H14N3O4F2 [M + H] calculated: 338.0947; found: 338.0947. HRMS (ESI) for C15H13N3O4F2Na [M + Na] calculated: 360.0766; found: 360.0766. For C15H13N3O4F2.0.7H2O.0.2C4H10O calculated: 52.03% C, 4.53% H, 11.52% N; found: 52.04% C, 4.48% H, 11.46% N. 7-(2-Deoxy-2-fluoro-ß-D-arabinofuranosyl)-5-fluoro-4-(thiophen-3-yl)- 7H-pyrrolo[2,3-d]pyrimidine (30e) Deprotection of 29e (478 mg, 0.85 mmol) as described for 28a gave compound 30e as a yellowish foamy solid. Yield 271 mg (90%). Compound 30e was crystallized from MeOH-water as ochry plates. M.p. 90-92 °C. [a]D +42.5 (c 0.442, DMSO). 1H NMR (499.8 MHz, DMSO-d6): 3.65 (ddd, 1 H, Jgem = 12.0, J5'b,4' = 5.0, JH,F = 0.7, H-5'b); 3.72 (ddd, 1 H, Jgem = 12.0, J5'a,4' = 4.0, JH,F = 1.6, H-5'a); 3.85 (dddd, 1 H, J4',3' = 5.7, J4',5' = 5.0, 4.0, JH,F = 0.9, H-4'); 4.42 (ddd, 1 H, JH,F = 19.1, J3',4' = 5.7, J3',2' = 4.2, H-3'); 5.24 (ddd, 1 H, JH,F = 52.8, J2',1' = 4.8, J2',3' = 4.2, H-2'); 6.82 (ddd, 1 H, JH,F = 13.3, 1.8, J1',2' = 4.8, H-1'); 7.74 (dd, 1 H, J5,4 = 5.1, J5,2 = 2.9, H-5-thienyl); 7.83 (ddd, 1 H, J4,5 = 5.1, J4,2 = 1.3, JH,F = 0.9, H-4-thienyl); 7.865 (t, 1 H, JH,F = 1.9, H-6); 8.37 (ddd, 1 H, J2,5 = 2.9, J2,4 = 1.3, JH,F = 0.7, H-2-thienyl); 8.87 (s, 1 H, H-2). 13C NMR (125.7 MHz, DMSO-d6): 60.48 (CH2-5'); 72.57 (d, JC,F = 23.0, CH-3'); 80.86 (d, JC,F = 17.0, CH-1'); 83.22 (d, JC,F = 5.9, CH-4'); 96.03 (d, JC,F = 192.0, CH-2'); 103.99 (d, JC,F = 15.0, C-4a); 111.64 (dd, JC,F = 31.1, 3.3, CH-6); 127.36 (CH-5-thienyl); 128.02 (d, JC,F = 10.8, CH-4-thienyl); 129.77 (d, JC,F = 10.8, CH-2-thienyl); 138.88 (C-3-thienyl); 141.52 (d, JC,F = 246.7, C-5); 147.23 (d, JC,F = 3.3, C-7a); 151.75 (d, JC,F = 4.0, C-4); 151.98 (CH-2). 19F NMR (470.3 MHz, DMSO-d6): -198.73 (ddd, JF,H = 52.8, 19.1, 13.3); -160.48 (s). MS (ESI) m/z: 354 (M + H), 376 (M + Na). HRMS (ESI) for C15H14N3O3F2S [M + H] calculated: 354.0718; found: 354.0718. HRMS (ESI) for C15H13N3O3F2SNa [M + Na] calculated: 376.0538; found: 376.0537. For C15H13N3O3F2S.0.2H2O.0.55CH4O calculated: 49.86% C, 4.20% H, 11.22% N; found: 49.92% C, 4.15% H, 11.16% N. This work is a part of the research project Z4 055 0506 from the Academy of Sciences of the Czech Republic. It was supported by the the Czech Science Foundation (P207/11/0344) and by Gilead Sciences, Inc. The authors thank Dr. I. Votruba (IOCB) and Dr. T. Cihlar, Dr. G. Birkus and Dr. R. Mackman (Gilead) for cytostatic and antiviral screening. REFERENCES 1. a) Hocek M., Holý A., Votruba I., Dvoráková H.: J. Med. Chem. 2000, 43, 1817; b) Hocek M., Holý A., Votruba I., Dvoráková H.: Collect. Czech. Chem. Commun. 2001, 66, 483; c) Hocek M., Nau. P., Pohl R., Votruba I., Furman P. A., Tharnish P. M., Otto M. J.: J. Med. 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M., van Boom J. H.: Tetrahedron Lett. 1980, 21, 1571. 23. Bhattacharya B. K., Rao T. S., Revankar G. R.: J. Chem. Soc., Perkin Trans. 1 1995, 1543. 24. Seela F., Xu K., Chittepu P.: Synthesis 2006, 2005. 25. Campeau L. C., O'Shea P. D.: Synlett 2011, 57. 26. Tann C. H., Brodfuehrer P. R., Brundidge S. P., Sapino C., Jr., Howell H. G: J. Org. Chem. 1985, 50, 3644. Petr NAUS1, Pavla PERLÍKOVÁ2, Radek POHL3 and Michal HOCEK4,* Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Gilead Sciences & IOCB Research Center, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic; e-mail: 1 [email protected], 2 [email protected], 3 [email protected], 4 [email protected] Received April 20, 2011 Accepted May 31, 2011 Published online July 7, 2011 Dedicated to Professor Antonín Holý on the occasion of his 75th birthday. (c) 2011 Institute of Organic Chemistry and Biochemistry [ Back To TMCnet.com's Homepage ]