Premium
Synthesis and biological evaluation of novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides as potential antiviral agents
Author(s) -
Ko Ok Hyun,
Hong Joon Hee
Publication year - 2004
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200400918
Subject(s) - chemistry , catalysis , cytosine , stereochemistry , biological activity , cytotoxicity , bromide , combinatorial chemistry , dna , organic chemistry , biochemistry , in vitro
Novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides were synthesized in this study. The introduction of two methyl groups in the 2′‐ and 3′‐position was accomplished by a Horner‐Wadsworth‐Emmons reaction and isopropenyl magnesium bromide addition, respectively. The construction of the required 4′‐quaternary carbon was carried out using a [3, 3]‐sigmatropic rearrangement. Bis‐vinyls were successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. The antiviral activities of the synthesized compounds were evaluated against HIV‐1, HSV‐1, HSV‐2 and HCMV. Compound 30 displayed moderate anti‐HCMV activity (EC 50 = 30.1 μg/mL), without exhibiting any cytotoxicity at up to 100 μM.