Nucleosteroids: Synthesis of purinyl-steroid derivatives under mitsunobu reaction conditions

Abstract

The feasibility of using the Mitsunobu reaction for coupling of purines with steroids to obtain nucleosteroids was investigated in the particular case of 6-chloropurine and cholesterol. Three principal products were obtained: 3βbT-(6-chloropurin-9-yl)-5-cholestene (1), 3α-(6-chloropurin-9-yl)-5-cholestene (2), and 6βbT-(6-chloropurin-9-yl)-3,5-cyclocholestane (3), isolated with 10.5%, 22.7%, and 12.6% yield, respectively. The stereochemical and structural diversity of the coupling products are explained by the formation of a homoallylic carbocation through participation of the double bond of cholesterol.