An Efficient Conversion of Camptothecin to 10-Hydroxycamptothecin

摘要

The alkaloid camptothecin (1) received intense synthetic and clinical interest following the 1966 report of its isolation, structure determination, and strong anti-tumor activity. This interest waned when the compound was found to have severe clinicaltoxicity caused in part by its lack of solubility, but it returned following the 1985 report that 1 acts by inhibiting DNA topoisomerase I, which governs the topology of DNA reassembly following replication. This represented a new and potentially selective mode of action since the enzyme is present in much larger quantities in transformed, neoplastic cells than in normal cells. Consequently, a number of groups began investigating derivatives of 1 in hopes of finding one that retained the ability to. inhibit topoisomerase I but avoided toxicity problems.