Efficient synthesis of PBD conjugate agents

ORGN 698

Wan-Ping Hu1, Chung-Yu Chen2, and Jeh-Jeng Wang, jjwang@kmu.edu.tw2. (1) Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, (2) Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a group of potent, naturally occurring antitumor antibiotics produced by Streptomyces species. Recently, we reported the total synthesis of a series of novel PBD-indole conjugates. The biological studies showed that these agents have potential for use as highly potent broad-spectrum antitumor/anticancer compounds to inhibit the growth of a variety of cancer cell lines. In this presentation, we will describe the improved synthesis of these conjugates. The three-step synthesis, debenzylation of MOM-protected 8-benzyloxy-PBD, coupled with indoles, reduction of ether-protected conjugates generates the title compounds in high yields.