CONJUGATE ADDITION OF TRIMETHYLSILYLMETHYL CUPRATES TO ARTEMISINIC ACID - HOMOLOGATION AND SUBSEQUENT CONVERSION TO 9-BETA-MODIFIED ARTEMISININ ANALOGS

Conjugate addition to the acrylic acid moiety of artemisinic acid 2 wa s made possible by in situ protection as a silyl ester followed by tre atment with a trimethylsilylmethyl cuprate such as (TMSCH2)C4H9CuLi . LiX, where X = CN or I. After deprotective workup, the homologated car boxylic acid 9 was obtained in excellent yields. Photoxygenation and a cid treatment of 9 then led to the facile preparation of potent 9 beta -modified analogs of the naturally occurring antimalarial agent artemi sinin.