2'-메칠 및 4'-페닐 측쇄를 가진 새로운 카보사이클릭 뉴크레오사이드의 합성 및 항바이러스 약효검색

Synthesis and Antiviral Activity of Novel 2'-Methyl and 4'-Phenyl Branched Carbocyclic Nucleosides

In this study, a series of 2',4'-doubly branched carbocyclic nucleosides (8,9,10) were synthesized from simple acyclic ketone derivative as starting material. The installation of the 4'-quaternary carbon needed was carried out using a (3,3)- sigmatropic rearrangement. In addition, the introduction of a methyl group in the 2'- position was accomplished by Grig-nard reaction. Bis-vinyl was successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine, uracil) were efficiently coupled with the use of a Pd(0) catalyst. Although all the synthesized compounds were assayed against several viruses, only cytosine analogue 9 showed weak antiviral viral activity (EC50=45.4μM) against CoxB3 virus.