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 identified as a promising candidate. A practical, scalable synthesis of I that limits the isolation of cytotoxic compounds to only that of the final product is described. The convergent process features a novel phase transfer-promoted glycosylation of aglycone core (4); subsequent hydrolysis provides anhydride (8). The hydrazine fragment (3), which is coupled with 8, is synthesized via a modification of existing procedures. The coupled product (2) is subsequently hydrogenated to provide 1 in excellent purity via direct crystallization (> 99.3 A%). (C) 2001 Elsevier Science Ltd. All rights reserved.