Synthetic Studies toward Biologically Active Quinones and Alkaloids

by Joo, Beomjun

Part 1 describes the synthesis and biological evaluation of small-molecule phosphatase inhibitors. The targets for the synthesized compounds are mainly Cdc25 phosphatases, which play a key role in regulating cell cycle and are often over-expressed in cancers. Highlights of the synthesis are the amide bond formation, the synthesis of secondary amines via o-Ns chemistry, the ring opening of the lactam by the amine, the preparation of various (iso)quinolinediones and the substitution reactions of (iso)quinolinediones with amines and thiols. The synthesis and reaction of isoquinonlinediones are particularly highlighted in the total synthesis of caulibugulones A-E. Biological assays established the (iso)quinolinediones as new phosphatase inhibitors with considerable selectivity against the Cdc25 family of DSPases. Part 2 describes the synthetic studies toward the total synthesis of parvistemonine, which represents one of the most challenging synthetic targets among Stemona alkaloids. The studies are mainly focused on the development of a fragmentation strategy aimed at the total synthesis of parvistemonine. Highlights of these studies are the synthesis of vinyl azides, the fragmentation reaction of tertiary alcohols and the use of the trimethylsilyl-methylene group as a directing group in the fragmentation reaction. These studies demonstrate a novel vinylogous azido alcohol fragmentation reaction in simple model systems and a regioselective fragmentation reaction of hydroxy indolines.