NUCLEOSTEROIDS - REACTION OF ACTIVATED PURINE-BASES WITH STEROIDAL REACTIVE CENTERS

The reaction of 16 alpha,17 alpha-epoxy-3 beta-hydroxy-5-pregnen-20-on e with 6-methyl thiopurine activated with sodium hydride leads to the coupling of the purine base with the carbonyl group at C-20 to give a steroidal nucleoside analog, which is termed ''nucleosteroid.'' In the presence of an excess of purine, a parallel reaction occurs in which the oxirane ring is opened, presumably by nucleophilic attack of an in termediate C-20 oxyanion, and yields as the main product of reaction a n oligomeric mixture of nucleosteroid units linked together by ether l inkages. Analogous reactions conducted with 3 beta-hydroxy-5-pregnen-2 0-one and with 3 beta,17 alpha-dihydroxy-5-pregnen-20-one gave minor a mounts or only traces of the corresponding coupling adduct, and oligom erization did nor occur. This behavior is interpreted in terms of the conformational differences showed by the different steroids to the att ack by the purine. (C) 1996 by Elsevier Science Inc.