Development of anti-XDR-TB leads based on catalytic asymmetric synthesis and chemical biology

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460168
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: WATANABE Takumi 公益財団法人微生物化学研究会, 微生物化学研究所, 部長 (80270544)
• Co-Investigator(Renkei-kenkyūsha): ISHIZAKI Yoshimasa (公財)微生物化学研究会, 微生物化学研究所 第2生物活性研究部, 主任研究員 (10414103) ; UMEZAWA Yoji (公財)微生物化学研究会, 微生物化学研究所 分子構造解析部, 部長 (60160313) ; SAKAMOTO Shuichi (公財)微生物化学研究会, 微生物化学研究所 沼津支所, 上級研究員 (60346070)
• Research Collaborator: Gandamala Ravi (公財)微生物化学研究会, 微生物化学研究所 有機合成研究部, 博士研究員 ; Wang Lu (公財)微生物化学研究会, 微生物化学研究所 有機合成研究部, 博士研究員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 触媒的不斉合成 / ケミカルバイオロジー / XDR-TB / 抗結核薬 / 構造活性相関

Outline of Final Research Achievements

Initially, caprazamycin derivatives which is not accessible by semi-synthetic strategy starting from naturally-occurring captazamycin were prepared based on the catalytic asymmetric synthetic route to caprazol and caprazamycin; caprazol derivatives with longer aliphatic side chain installed on one of the nitrogen atoms embedded in the seven-membered lactam core were successfully synthesized.
Then, catalytic asymmetric synthesis of CPZEN-45 was accomplised. In the synthetic route, a complex comprising Zn and chiral linked-BINOL ligand was found to be effective for the aldol reaction to construct the beta-hydroxyamino acid substructure to show excellent diastereoselectivity.

Free Research Field

有機化学