An alternative synthetic method for 4'-C-ethynylstavudine by means of nucleophilic substitution of 4'-benzoyloxythymine nucleoside.
For the synthesis of 2',3' -didehydro-3' -deoxy-4' -C-ethynylthymidine (8: 4' -Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-l-glycero-pent-4-enofuranosyl)thymine with Pb(OBz)4 allowed the introduction of a 4'-benzoyloxy leaving group, nucleophilic substitution at the 4' -position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (11) and Me3SiC identical with CAl(Et)Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (15) stereoselectively in 62% yield.
Haraguchi
Kazuhiro
K
School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan. harakazu@pharm.showa-u.ac.jp
Sumino
Masanori
M
Tanaka
Hiromichi
H
D002625:Chemistry, Organic / Q000379:methods*; D004852:Epoxy Compounds / Q000737:chemistry; D008745:Methylation; D009705:Nucleosides / Q000737:chemistry*; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013941:Thymine / Q000737:chemistry
C505960:4'-ethynylstavudine; D004852:Epoxy Compounds; D009705:Nucleosides; D018119:Stavudine; D013941:Thymine; C064455:dimethyldioxirane