Hiroaki Tagawa

Antitumor Agents. VI. Synthesis and Antitumor Activity of Ring A-, Ring B-, and Ring C-Modified Derivatives of Camptothecin

Eleven ring A-, ring B-, and ring C-modified analogues of the antitumor alkaloid camptothecin (1) were prepared and evaluated for cytotoxicity and antitumor activity against P388 mouse leukemia. Among the six ring A-modified analogues, hexacyclic compound (14) retained the same order of activity as (1). Most of the ring B- and ring C-modified analogues displayed greatly reduced activity, whereas compound (39), which has an alkylidene group at position 5, was found to be as active as (1). These results confirmed the necessity of the intact rings A, B, and C of (1) for antitumor activity. Further, the higher activity of (14) and (39) suggest that the «northern» part of the camptothecin molecule may be a suitable site for functionalization to obtain more potent analogues of (1)

Antitumour agents. Part 2. Asymmetric synthesis of (S)-camptothecin

The total synthesis of (S)-camptothecin by a novel diastereoselective ethylation process is described.