Perchloric acid induced epimerisation of the thevinones: an improved synthesis of 7 beta-dihydrothevinones

The region above and away from C7 in the orvinols is known to be of particu lar importance in determining the mu-opioid receptor profile of this import ant class of opioids. However it has been difficult to explore this site du e to the relative inaccessibility of 7 beta-substituted compounds. Here we report that perchloric acid induced epimerisation of the 7 alpha-ketones (d ihydrothevinones) allows considerably improved access to a series of beta-k etones (beta-dihydrothevinones). The extent of epimerisation of the 7 alpha -ketone is determined by the degree of steric bulk in both the 6,14-bridge and in the ketone side chain. (C) 2000 Elsevier Science Ltd. Ail rights res erved.