Practical synthesis of a potent indolocarbazole-based, DNA topoisomerase inhibitor

DNA topoisomerase I inhibitors are currently under investigation as cancer chemotherapy agents of which indolocarbazole glycoside (1) has been identif ied as a promising candidate. A practical, scalable synthesis of I that lim its the isolation of cytotoxic compounds to only that of the final product is described. The convergent process features a novel phase transfer-promot ed glycosylation of aglycone core (4); subsequent hydrolysis provides anhyd ride (8). The hydrazine fragment (3), which is coupled with 8, is synthesiz ed via a modification of existing procedures. The coupled product (2) is su bsequently hydrogenated to provide 1 in excellent purity via direct crystal lization (> 99.3 A%). (C) 2001 Elsevier Science Ltd. All rights reserved.