Total synthesis and structure elucidation of anti-microbial FO-7711CD6 by using chirality-returning synthetic process

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460025
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Tokyo University of Science
• Principal Investigator: UCHIRO Hiromi 東京理科大学, 薬学部, 教授 (00307711)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 不斉全合成 / 構造決定 / 生物活性物質 / 抗菌活性物質 / 大環状化合物 / 芳香族求核置換反応 / 付加脱離型反応 / 高ひずみ化合物

Outline of Final Research Achievements

Asymmetric total syntheses of GKK1032A2 and its three kinds of stereoisomers were investigated to elucidate the stereochemistry of anti-microbial compound FO-7711CD6. A construction of highly strained 13-membered macrocycle of GKK1032A2 was achieved by Ullmann etherification. The obtained trace amount of macrocycle was successfully converted to the desired final product and its 1H-NMR spectrum and HRMS are in good agreement with that of GKK1032A2. However, the poor yield of macrocyclizaion is a serious problem for the completion of total synthesis. Therefore, a new efficient method for the construction of 13-membered macrocycle utilizing nucleophilic aromatic substitution of arene chromium complex was investigated and successfully developed. End games toward the total synthesis of GKK1032A2 in large scale are now in progress. Three kinds of stereoisomers of GKK1032A2 will be synthesized by the developed method to elucidate the precise stereochemistry of FO-7711CD6.

Free Research Field

有機合成化学