Divergent syntheses of Natural Iridoids

Abstract

Iridoids are a family of monoterpene secondary metabolites found in a large number of plant families usually as glycoside. Iridoid families could be found in folk medicinal plants used as bitter tonics, sedatives, hypotensives, remedies for wounds and skin disorders. Recent, their broad biological activities and their key role in biosynthesis of alkaloids make them attractive targets for synthetic chemists and biologists. The most of iridoids structurally consist of highly oxygenated cis-fused cyclopenta[c]pyran skeleton. In 2010, iridoid natural product, jatamanins were first isolated from extract of Nardostachys jatamansi. These jatamanins commonly have cis-fused cyclopenta[c]pyran, but they have different oxidation states. Total syntheses of jatamanins have not been accomplished since isolation. Herein, we described the enantioselective total syntheses of jatamanins in a divergent manner. First total syntheses of jatamanin A, F, G, and J and syntheses of gastrolactone and nepetalactone were accomplished. Divergent syntheses of iridoids could be easily transformed from differentiating oxidation state of cis-fused cyclopenta[c]pyran intermediate. The key features of our syntheses involve (1) divergent synthesis of various jatamanins via common intermediate, (2) stereoselective Pd(0)-catalyzed allylic alkylation, (3) consecutive diastereoselective epoxidation and epoxide opening which provided contiguous four stereogenic centers.