OXIDATIVE PHOTOCHEMICAL DECARBOXYLATION OF ZARAGOZIC ACID-A

A unique decomposition reaction of the novel squalene synthase inhibit ors called zaragozic acids has been studied. Under very mild condition s, e.g. by merely exposing their solutions to air and visible light at ambient temperature, these compounds, characterized by the [3.2.1]oct ane-4,6,7-trihydroxy-3,4,5-tricarboxylic acid core, rapidly decompose. As relatively stable intermediates in the cascade of decomposition, t he biologically active yclo[3.2.1]octane-6,7-dihydroxy-4-keto-5-caroxy lic acid (or 3,4-decarboxy-4-dehydro) derivatives of these compounds h ave been isolated in ca. 20% yield. Derivatization on the highly react ive 4-carbonyl group yields stable derivatives, several of which are p otent inhibitors of squalene synthase. Further decomposition results i n the elimination of C3 and C4 atoms and the carboxylic acid on C5, th e oxidation of C5 to carboxylic acid and the liberation of the oxo gro up on C1. Specific results obtained with zaragozic acid A, a key repre sentative of the family of these potent cholesterol-lowering agents, a re presented in this study.