Synthesis and anti-HIV activity of 4'-C-ethynyl-2'-deoxy-4'-thio-nucleosides.
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).
Haraguchi
Kazuhiro
K
School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, Japan.
Shimada
Hisashi
H
Akutsu
Genta
G
Kimura
Keigo
K
Tanaka
Hiromichi
H
Hamasaki
Takayuki
T
Baba
Masanori
M
Gullen
Elizabeth A
EA
Dutschman
Ginger E
GE
Cheng
Yung-Chi
YC
Balzarini
Jan
J
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000494:pharmacology
D019380:Anti-HIV Agents; D013872:Thionucleosides