Reaction of Cytidine with Cyanopropargylic Alcohols: Synthesis of Functionalized Cytidine Cyclic Ketals

Abstract

Cytidine reacts with one or two molecules of cyanopropargylic alcohols under mild conditions (K₂CO₃, DMF, 20–25 °C, 10–48 h) by the hydroxy groups of the ribose moiety to afford representatives of the two novel families of cytidine cyclic ketals. The first ones (53–76% yields) are formed with participation of the two vicinal hydroxyl groups (at 2′,3′-cis-positions) only. The second ones (7–21% yields) represent the adducts of cytidine with two molecules of cyanopropargylic alcohols involving all the three hydroxyl groups.

Key words

cytidine - cyanopropargylic alcohols - nucleophilic addition - cyclization - cyclic ketals

• References

• 1a Trovarelli G, Palmerini CA, Floridi A, Piccinin GL, De Medio GE. Neurochem. Res. 1987; 12: 227
• 1b Powner MW, Sutherland JD, Szostak JW. Synlett 2011; 1956
• 2a Takenuki K, Matsuda A, Ueda T, Sasaki T, Fujii A, Yamagami K. J. Med. Chem. 1988; 31: 1063
• 2b Baker CH, Banzon J, Bollinger JM, Stubbe J, Samano V, Robins MJ, Lippert B, Jarvi E, Resvick R. J. Med. Chem. 1991; 34: 1879
• 2c McCarthy JR, Matthews DP, Stemerick DM, Huber EW, Bey P, Lippert BJ, Snyder RD, Sunkara PS. J. Am. Chem. Soc. 1991; 113: 7439
• 2d Matsuda A, Takenuki K, Tanaka M, Sasaki T, Ueda T. J. Med. Chem. 1991; 34: 812
• 2e Matsuda A, Nakajima Y, Azumat A, Tanaka M, Sasaki T. J. Med. Chem. 1991; 34: 2917
• 2f Azuma A, Nakajima Y, Nishizono N, Minakawa N, Suzuki M, Hanaoka K, Kobayashi T, Tanaka M, Sasaki T, Matauda A. J. Med. Chem. 1993; 36: 4183
• 2g Hattori H, Tanaka M, Fukushima M, Sasaki T, Matsuda A. J. Med. Chem. 1996; 39: 5005
• 2h Hattori H, Nozawa E, Iino T, Yoshimura Y, Shuto S, Shimamoto Y, Nomura M, Fukushima M, Tanaka M, Sasaki T, Matsuda A. J. Med. Chem. 1998; 41: 2892
• 2i Matsuda A, Sasaki T. Cancer Sci. 2004; 95: 105
• 2j Murata D, Endo Y, Obata T, Sakamoto K, Syouji Y, Kadohira M, Matsuda A, Sasaki T. Drug Metab. Dispos. 2004; 32: 1178
• 2k Yonemura Y, Endo Y, Obata T, Sasaki T. Cancer Sci. 2007; 98: 11
• 2l Meike S, Yamamori T, Yasui H, Eitaki M, Matsuda A, Morimatsu M, Fukushima M, Yamasaki Y, Inanamil O. Mol. Cancer 2011; 10: 92
• 3a Kleemann A, Engel J, Kutscher B, Reichert D. Pharmaceutical Substances: Syntheses, Patents, Applications . Thieme; Stuttgart: 2001: 332-333
• 3b Kleemann A, Engel J, Kutscher B, Reichert D. Pharmaceutical Substances: Syntheses, Patents, Applications . Thieme; Stuttgart: 2001: 956-958
• 3c Das P, Wolff RA, Abbruzzese JL, Varadhachary GR, Evans DB, Vauthey JN, Baschnagel A, Delclos ME, Krishnan S, Janjan NA, Crane CH. Radiat. Oncol. 2006; 1: 41
• 4 Ando T, Ichikawa J, Okamoto A, Tasaka K, Nakao A, Hamada Y. J. Orthop. Res. 2005; 23: 964
• 5a De Clercq E, Holy A. J. Med. Chem. 1979; 22: 510
• 5b Wnuk SF, Yuan C.-S, Borchardt RT, Balzarini J, De Clercq E, Robins MJ. J. Med. Chem. 1994; 37: 3579
• 6a Baker CH, Banzon J, Bollinger JM, Stubbe J. J. Med. Chem. 1991; 34: 1879
• 6b De Fallois LL. H, Décout J-L, Fontecave M. J. Chem. Soc., Perkin Trans. 1 1997; 2587
• 6c Azhar KF, Gudrat-E-Khuda M, Zuberi R. J. Chem. Soc. Pak. 2002; 24: 57; Chem. Abstr. 2002, 138, 137501
• 6d Crane CM, Hirsch AK. H, Alphey MS, Sgraja T, Lauw S, Illarionova V, Rohdich F, Eisenreich W, Hunter WN, Bacher A, Diederich F. ChemMedChem 2008; 3: 91
• 7a Furukawa Y, Miyashita O, Honjo M. Chem. Pharm. Bull. 1974; 22: 2552
• 7b Olomucki M, Le Gall JY, Colinart S. Tetrahedron Lett. 1984; 25: 3471
• 7c Roques P, Le Gall JY, Lacombe L, Olomucki M. J. Org. Chem. 1992; 57: 1579
• 8a Amarnath V, Broom AD. Chem. Rev. 1977; 77: 183
• 8b Ott J, Sella F. Bioorg. Chem. 1981; 10: 82
• 8c Fogt J, Januszczyk P, Onishi T, Izawa K, Boryski J. ARKIVOC 2009; (iii): 198
• 9 Trofimov BA, Nosyreva VV, Shemyakina OA, Mal’kina AG, Albanov AI. Tetrahedron Lett. 2012; 53: 5769
• 10a Hopf H, Witulski B. Functionalized Acetylenes in Organic Synthesis - The Case of the 1-Cyano- and 1-Halogenoacetylenes. In Modern Acetylene Chemistry. Stang PJ, Diederich F. VCH; Weinheim: 1995: 33-66
• 10b Trofimov BA, Mal’kina AG. Heterocycles 1999; 51: 2485
• 10c Trofimov BA, Andriyankova LV, Belyaeva KV. Chem. Heterocycl. Compd. (Engl. Transl.) 2012; 48: 147
• 11a Landor SR, Demetriou B, Grzeskowiak R, Pavey D. J. Organomet. Chem. 1975; 93: 129
• 11b Trofimov BA, Andriyankova LV, Shaikhudinova SI, Kazantseva TI, Mal’kina AG, Zhivet’ev SA, Afonin AV. Synthesis 2002; 853