Synthesis and anti-HIV activity of 4'-C-ethynyl-2'-deoxy-4'-thio-nucleosides

Nucleic Acids Symp Ser (Oxf). 2009:(53):97-8. doi: 10.1093/nass/nrp049.

Abstract

Synthesis of 4'-C-ethynyl-2'-deoxy-4'-thionucleosides was carried out based on electrophilic glycosidation using 4-C-ethynyl-4-thiofuranoid glycal. The glycal 15 was prepared as follows: oxidative cleavage of 6 with Pb(OAc)(4) forming the aldehyde 7, aldol reaction of 7 and subsequent silylation to furnish 8, conversion of the formyl group of 8 into an ethynyl group, and finally beta-elimination of the resulting 14 with t-BuLi. The glycosyl donor 16 was prepared by silyl-protection of 15. Electrophilic glycosidation was performed between silylated N(4)-acetylcytosine and 16 in the presence of N-iodosuccinimide. Radical-mediated removal of the introduced iodine atom followed by deprotection gave 4'-C-ethynyl-2'-deoxy-4'-thiocytidine (18).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Thionucleosides / chemical synthesis*
  • Thionucleosides / pharmacology

Substances

  • Anti-HIV Agents
  • Thionucleosides