Synthesis of novel 3'-C-methyl-apionucleosides: an asymmetric construction of a quaternary carbon by Claisen rearrangement.
The synthesis of 2,3-dideoxy-3-C-(hydroxymethyl)-3-C-methyl-D-glycero-tetrofuranosyl++ + nucleosides was accomplished in high enatiomeric purity (98.5% ee) via [3,3]-sigmatropic Claisen rearrangement of (E)(S)-5-benzyloxy-1-tert-butyldimethylsilanyloxy-4-methyl-pent-3- en-2-ol prepared from 2,3-O-isopropylidene-D-glyceraldehyde. The synthesized nucleosides were assayed against human immunodeficiency virus (HIV) and hepatitis B virus in human peripheral blood mononuclear (PBM) and 2.2.15 cells, respectively. 6-Amino-9-[2,3-dideoxy-3-C-(hydroxymethyl)-3-C-methyl-beta-D-glycero- tetrofuranosyl]-2-fluoropurine shows moderate antiviral activity (EC50 = 2.55 microM) against HIV-1 strains and 6-amino-9-[3-deoxy-3-C-(hydroxymethyl)-3-methyl-alpha-D-glycero-tetro furanosyl]-2-fluoropurine exhibits potent anti-HIV activity (EC50 = 0.073 microM) with significant cytotoxicity (IC50 = 1.0 microM).
Hong
J H
JH
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens 30602, USA.
Gao
M Y
MY
Choi
Y
Y
Cheng
Y C
YC
Schinazi
R F
RF
Chu
C K
CK
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D015497:HIV-1 / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000821:virology; D011684:Purine Nucleosides / Q000138:chemical synthesis*
D019380:Anti-HIV Agents; D011684:Purine Nucleosides