Camptothecin analogues prepn. - involving alkylation prior to reduction and lactonization of chloro-camptothecin precursors

摘要

A cpd. of formula (I) (where R2 is H2 R is an alkyl residue other than t-butyl or methyl) is alkylated to give a cpd. (I) (where R2 is opt. unsatd. 1-5C alkyl. Opt. (II) is reduced to a cpd. of partial formula (III), and opt. (III) is further converted into the lactone of partal formula (IV) with the aid of trifluroacetic acid. Cpds. (IV) are 20-deoxy-7-chlorocamptothecin analogues. Camptothecin and camptothecin-like cpds. have interesting effects on RNA synthesis. Alkylating at the stage of the camptothecin synthesis corresponding to the cpd. (I) rather than carrying out the alkylation on lactonized cpds. avoids side-reaction and improves yields. In an example (I;R=iPr) is used to prepare (II;R=i-Pr, R2=Et) in 75% yield.