Studies on the Generation of Unnatural C-Nucleosides with 1-Alkynyl-2-deoxy-D-riboses Mauro F. A. Adamo* and Roberto Pergoli Centre for Synthesis and Chemical Biology (CSCB), Department of Pharmaceutical and Medicinal Chemistry, The Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Dublin, Ireland madamo@rcsi.ie Received July 26, 2007 ABSTRACT 1-Alkynyl-2-deoxy-D-riboses 7 and 8 were independently synthesized and subsequently used to generate several novel C-nucleosides. The discovery of new chemotherapeutic treatments for controlling microbial infections is an important topic in medicinal chemistry. Nucleosides and nucleoside biochem- istry lie at the heart of life and life propagation, and therefore nucleoside analogues have attracted much attention as potential antimicrobial and antitumor agents. Many nucleo- sides of natural origin have been found to be bioactive. Bredinine 1 (Mizoribine) is an imidazole nucleoside antibiotic clinically used as an immunosuppressant; 2 Toyocamycin, 3 Mycalisin A, 4 and Thiosangivamycin 3 are three naturally occurring nucleosides exerting potent antiviral and antine- oplastic activity; Pseudouridine, 5 Showdomycin, 6 Pyrazofu- rin, 7 and Tiazofurin 8 have been shown to possess a wide range of medicinal properties, including antibiotic, antiviral, and antitumor activity. C-Nucleosides belonging to the 2-deoxy-D-ribose series have been scarcely explored and at present no data are available on the biological activity of nucleosides of the R-anomeric series. 9 In recent times interest increased on the medicinal chemistry of alkynyl-substituted (1) Mizuno, K.; Tsujino, M.; Takada, M.; Hayashi, K.; Atsumi, K.; Asano, K.; Matsuda, T. J. Antibiot. 1974, 27, 775. (2) Amenmiya, H.; Itoh, H. In ImmunosuppressiVe Drugs: DeVelopments in Anti-rejection Therapy; Thompson, A. W., Starzt, T. E., Eds.; Edward Arnord: London, UK, 1993; p 161. Giruber, S. A. Immunol. ReV. 1992, 129, 5. Turka, L. A.; Dayton, J.; Sinclair, G.; Thomson, C. B.; Mitchell, B. S. J. Clin. InVest. 1991, 87, 940. (3) Krawczyc, S. H.; Nassiri, M. R.; Kucera, L. S.; Kern, E. R.; Ptak, R. G.; Wotring, L. L.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 1995, 38, 4106. (4) Kato, Y.; Fusetani, N.; Matsunaga, S.; Hashimoto, K. Tetrahedron Lett. 1985, 29, 3483. (5) Buchanan, J. G.; Wightman, R. H. Top. Antibiot. Chem. 1982, 6, 229. (6) Mubarak, A. M.; Brown, D. M. Tetrahedron Lett. 1981, 22, 683. (7) Shaban, M. A. E.; Nasr, A. Z. AdV. Heterocycl. Chem. 1997, 68, 223. (8) Sallam, M. A. E.; Luis, F. F.; Cassady, J. M. Nucleosides Nucleotides 1998, 17, 769. (9) Adamo, M. F. A.; Adlington, R. M.; Baldwin, J. E.; Day, A. L. Tetrahedron 2004, 60, 841. ORGANIC LETTERS 2007 Vol. 9, No. 22 4443-4446 10.1021/ol701794u CCC: $37.00 © 2007 American Chemical Society Published on Web 10/02/2007