Design and Synthesis of Pyrrolo[2,1-c][1,4]benzodiazepine Hybrid Agents

• Main Authors: lin fu lung, 林福隆
• Other Authors: wang jeh jeng
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/62092090806010682902

碩士 === 高雄醫學大學 === 藥學研究所 === 89 === The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs), a family of potent DNA-binding antitumor antibiotics, are produced by Streptomyces species. These drugs react covalently with DNA to form a N2-guanine adduct that lies within the minor groove of DNA. DC-81 is one of the best known example of the PBDs. Several synthetic approaches to DC-81 have been reported, however, most of them are tedious. Herein we would like to report a new synthesis of DC-81 completed in six steps from 4-benzyloxy-5-methoxy-2-nitrobenzoic acid (43). The overall yield was 35%(67% yield based upon the recovered starting material, at the fifth step). Besides, we have synthesized the DC-81 and indole carboxylate (IC) hybrid agents. Some of these drugs are in in vivo test.