Synthesis of 4'-Ethynyl-2'-deoxy-4'-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI.

ABSTRACT: The synthesis of 4'-ethynyl-2'-deoxy-4'-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation between 16 and the silylated nucleobases (N⁴-acetylcytosine, N⁶-benzoyladenine and N²-acetyl-O⁶-diphenylcarbamoylguanine) was carried out in the presence of N-iodosuccinimide (NIS) leading to the exclusive formation of the desired β-anomers 29, 33 and 36. Anti-HIV studies demonstrated that these 4'-thio nucleosides were less cytotoxic to T-lymphocyte (i.e. MT-4 cells) than the corresponding 4'-ethynyl derivatives of 2'-deoxycytidine (44), 2'-deoxyadenosine (45</

SUBMITTER: Haraguchi K 

PROVIDER: S-EPMC3686520 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature