Study towards development of anti-latent tuberculosis pyrroloindoles

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15956
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Osaka University
• Principal Investigator: Kimishima Atsushi 大阪大学, 薬学研究科, 特任助教(常勤) (20812134)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 天然物合成 / 酸化的脱芳香環化 / 連続反応 / 二量化反応 / 構造活性相関 / 潜在性結核菌

Outline of Final Research Achievements

Synthetic study of verticillins with the aim of structure-activity relationship analysis was conducted. As a result, we found a new method to construct C3a acetoxy hexahydropyrroloindole skeleton via tandem oxidative cyclization/acetoxylation of tryptophan and tryptamine derivatives. This synthetic method was also applied to the natural product synthesis, and the short step asymmetric synthesis of (-)-protubonine B was achieved. Furthermore, we have obtained new knowledge of oxidative dimerization of tryptamine derivatives under unique reaction conditions inspired by the developed tandem reaction.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

結核菌は、感染部位の低酸素環境下で潜在化し、既存の薬剤に抵抗性を示すことが知られている。また、この潜在性結核菌への感染者は実に世界人口の約1/3に上る。そのため、潜在化した結核菌にも有効な新規医薬シーズの探索は極めて重要な課題である。 本課題では、結核菌と相同性の高いMycobacterium属細菌に対して活性を示すverticillin類の合成および構造活性相関研究に向け、独自に開発した酸化的脱芳香環化反応を基盤としたピロロインドール類の合成を行った。