Design and synthesis of novel 2',3'-dideoxy-4'-selenonucleosides as potential antiviral agents.
On the basis of potent anti-HIV activity of 2',3'-dideoxynucleosides (ddNs), their bioisosteric analogues, 2',3'-dideoxy-4'-selenonucleosides (4'-seleno-ddNs) were first synthesized from a chiral template, d-glutamic acid using stereoselective ring-closure reaction of the dimesylate with Se(2-) and Pummerer type condensation of the selenoxide with nucleobases as key steps. X-ray crystallographic analysis indicated that 4'-seleno-ddNs adopted the same C2'-endo/C3'-exo (South) conformation as anti-HIV active ddNs, but did not show anti-HIV activity, indicating that RT seems to prefer the C2'-exo/C3'-endo (North) conformation on binding with their triphosphates.
Jeong
Lak Shin
LS
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea. lakjeong@ewha.ac.kr
Choi
Yoo Na
YN
Tosh
Dilip K
DK
Choi
Won Jun
WJ
Kim
Hea Ok
HO
Choi
Jungwon
J
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006678:HIV / Q000187:drug effects; D008956:Models, Chemical; D015394:Molecular Structure; D012643:Selenium / Q000737:chemistry*
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D012643:Selenium