Diversification of structurally significant cycloartane-type triterpenes: exploiting beddomeilactone

Abstract

The cycloartane-type triterpenes are a structurally important class of natural products with diverse biological activity. Here, we present synthetic strategies and chemical modifications for obtaining a number of recently reported cycloartane-type triterpenes, along with various close-to-natural novel derivatives. The naturally abundant beddomeilactone (1) serves as the key resource for most transformations. Notably, the linear sequences we put forward for synthesising three natural products from 1, include the selective reduction of 1 to generate the 2 with desired stereochemistry, the lactonization of 2 gives 3 qualitatively, and a selective olefin reduction of 3 gives 11. Further selective olefin reduction of 1 and 2 was carried out in order to produce dihydro-analogues (15 and 17). Acid-catalyzed esterification of 1 led to retro-aldol, forming novel analogue 18; also synthesised the expected ester derivative 5. Subsequent transformations, such as epoxidation, lactone ring opening, and amidation, produced diverse synthetic analogues (19–21). We also efficiently converted compound 4 into 2,4-epi-­binectarilactone (22), a structural analogue of 3.