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Synlett 2004(12): 2147-2150  
DOI: 10.1055/s-2004-832807
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Reactions of Allenic Sulfone-Modified Thymidine: The First Allenic Sulfone to Alkylate Deoxyadenosine

Sanjib Bera, Tanmaya Pathak*
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
Fax: +91(3222)282252; e-Mail: tpathak@chem.iitkgp.ernet.in;
Further Information

Publication History

Received 29 June 2004
Publication Date:
21 September 2004 (online)

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Abstract

3′-(S)-(allenic sulfonyl)-5′-benzoyl-3′-deoxythymidine has been synthesized from 1-(5-O-trityl-3-O-mesyl-2-deoxy-β-d-threopentofuranosyl) thymine via 3′-(S)-(propargylthio)-5′-trityl-3′-deoxythymidine in six steps. 3′-(S)-(allenic sulfonyl)-3′-deoxy­thymidine reacts very efficiently with a wide array of nucleophiles. This is also the first report on the alkylation of adenine moiety by some allenic sulfone modified compounds.

Key words

reactive nucleosides - allenic sulfone - alkylating nucleo­side

12

Compound 9: 1H NMR (360 MHz, CDCl3 + D2O): δ = 7.55 (s, 1 H, H-6), 6.13 (dd, J = 4.7, 7.0 Hz, 1 H, H-1′), 4.06-3.96 (m, 2 H), 3.87 (dd, J = 2.6, 11.9 Hz, 1 H), 3.73 (q, 1 H, J = 7.9 Hz), 3.36 (m, 2 H, SCH2), 2.65 (m, 1 H), 2.51 (m, 1 H), 2.32 (t, J = 2.6 Hz, 1 H, acetylenic), 1.91 (s, 3 H, CH3). 13C NMR (90 MHz, CDCl3): δ = 164.2, 150.5, 136.6, 110.7, 85.5 (C-1′), 85.5 (acetylene), 79.6 (C-4′), 72.0 (acetylene), 61.3 (C-5′), 40.9 (C-3′), 39.6 (C-2′), 19.4 (SCH2), 12.4 (CH3). HRMS (FAB+): m/z calcd for C13H17N2O4S [M + H]+: 297.0909; found: 297.0911.

13

Compound 12: mp 86-87 °C. 1H NMR (360 MHz, CDCl3): δ = 9.67 (s, 1 H, NH), 8.01-7.41 (m, 5 H, phenyl), 7.15 (s, 1 H, H-6), 6.26 (t, J = 6.2 Hz, 1 H, allene CH), 6.07 (t, J = 6.5 Hz, 1 H, H-1′), 5.59 (m, 2 H, =CH2), 4.79 (m, 2 H, H-4′, H-5′a), 4.56 (dd, J = 4.1, 12.2 Hz, 1 H, H-5′b), 4.07 (m, 1 H, H-3′), 2.97 (m, 1 H, H-2′a), 2.52 (m, 1 H, H-2′b), 1.64 (s, 3 H, CH3). 13C NMR (90 MHz, CDCl3): δ = 211.8 (=C=), 165.9 (ester CO), 163.8 (C-4), 150.1 (C-2), 135.4 (C-6), 133.6, 129.5, 129.1, 128.6 (phenyl), 111.3 (C-5), 96.3 (HC=), 86.5 (C-1′), 84.3 (=CH2), 77.0 (C-4′), 64.7 (C-5′), 63.7 (C-3′), 33.4 (C-2′), 12.1 (CH3). HRMS (FAB+): m/z calcd for C20H21N2O7S [M + H]+: 433.1061; found: 433.1061.

15

Methoxide ion adds to MeCCSO2Ph to produce MeC(OMe)2CH2SO2Ph, see ref. [8]

16

Compound 15: mp 169-170 °C. 1H NMR (360 MHz, DMSO-d 6): δ = 11.38 (s, 1 H), 8.30-7.08 (m, 10 H), 6.22 (t, J = 6.5 Hz, 1 H), 4.73-4.37 (m, 4 H), 2.83 (m, 1 H), 2.69 (s, 3 H), 2.64 (m, 1 H), 1.56 (s, 3 H). 13C NMR (90 MHz, DMSO-d 6): δ = 165.4 (benzoyl CO), 163.5, 150.3, 148.5, 136.5, 135.5, 133.6, 130.5, 129.3, 129.1, 128.8, 117.4, 111.7, 110.0, 84.3, 75.3, 65.1 (C-5′), 63.4, 31.4 (C-2′), 15.4, 11.8. HRMS (FAB+): m/z calcd for C23H25N4O7S [M + H]+: 501.1444; found: 501.1449. Compound 16: mp 103-104 °C. 1H NMR (360 MHz, CDCl3): δ = 10.57 (br s, 1 H), 7.95-7.02 (m, 9 H), 5.98 (t, J = 6.4 Hz, 1 H), 5.52 (s, 1 H), 5.37 (s, 1 H), 4.82 (m, 1 H), 4.69 (d, J = 12.2 Hz, 1 H), 4.58 (d, J = 14.7 Hz, 1 H), 4.50 (dd, J = 4.2, 12.2 Hz, 1 H), 4.33 (d, J = 14.7 Hz, 1 H), 3.86 (m, 1 H), 2.96 (m, 1 H), 2.33 (m, 1 H), 1.58 (s, 3 H). 13C NMR (90 MHz, CDCl3): δ = 165.9, 164.1, 150.5, 136.1, 135.4, 133.6, 130.4, 130.0, 129.5, 129.0, 128.6, 118.0, 114.1 (=CH2), 111.2, 86.5, 75.8, 64.9 (C-5′), 60.8, 56.8 (SO2CH2), 33.5 (C-2′), 12.1. HRMS (FAB+): m/z calcd for C23H25N4O7S [M + H]+: 501.1444; found: 501.1431.

17

Compound 20: A solution of 12 (0.140 g, 0.32 mmol) and 2′-deoxyadenosine (0.095 g, 0.36 mmol) in dioxane (15 mL) was stirred at r.t. for 2 d. Solvent was evaporated to dryness and the residue was purified over silica gel to give 19. Ac2O (0.6 mL, 6.40 mmol) was added to a solution of 19 in pyridine (15 mL) and the mixture was stirred at r.t. After 15 h the reaction mixture was worked-up in the usual way and the product was purified over silica gel to give 20 (0.120 g, 46%); mp 137-138 °C. 1H NMR (360 MHz, CDCl3): δ = 9.52 (s, 1 H), 7.97-7.07 (m, 8 H), 6.27 (dd, J = 6.1, 8.0 Hz, 1 H), 5.93 (t, J = 6.8 Hz, 1 H), 5.83 (s, 1 H), 5.66 (s, 1 H), 5.33 (m, 1 H), 4.79-4.12 (m, 9 H), 2.88-2.73 (m, 2 H), 2.58 (m, 2 H), 2.27 (s, 3 H), 2.09 (s, 3 H), 2.05 (s, 3 H), 1.61 (s, 3 H). 13C NMR (90 MHz, CDCl3): δ = 184.0, 170.4, 170.2, 165.9, 163.6, 149.9, 147.4, 144.2, 143.2, 138.0, 136.0, 134.5, 133.5, 129.6, 129.1, 128.6, 124.7 (=CH2), 121.2, 111.2, 87.1, 84.4, 82.7, 76.1, 74.3, 64.8 (CH2), 63.6 (C-5′, CH2), 61.3, 55.1 (CH2), 37.8 (CH2), 33.6 (CH2), 26.5, 20.8, 20.7 (2 peaks), 12.1. HRMS (FAB+): m/z calcd for C36H40N7O13S [M + H]+: 810.2405; found: 810.2410.