SYNTHETIC STUDIES ON BIOLOGICALLY-ACTIVE NATURAL-PRODUCTS USING PALLADIUM-PROMOTED CYCLIZATION

The use of palladium complexes as reagents for the synthesis of biolog ically active natural products has been under development for at least the past three decades, and many elegant total syntheses of structura lly complicated natural products, possessing pharmacologically importa nt properties, have been realized employing Heck reaction, cycloisomer ization process, and allylic alkylation reaction. In our recent contri bution to this area, we would like to describe total syntheses of aphi dicolin (diterpene), pumiliotoxin C (alkaloid), methyl pederate (left segment of mycalamides), hirsutene (sesquiterpene), stemodin (diterpen e), and methyl atis-16-en-19-oate (diterpene) using palladium-promoted cyclization as key step. Although the palladium-promoted cycloalkenyl ation reaction of an olefinic silyl enol ether is a powerful strategy for construction of polycyclic system, relatively little is known abou t successful application of the above reaction to biologically active natural product syntheses. Herein we report the development of novel p alladium-catalyzed cycloalkenylation reaction of cross-conjugated sily l enol ethers and its application to a tetracyclic diterpene synthesis .