Synthetic Study of Lactmaycins with Cathepsin B Inhibitory Activity

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K05518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Meiji University
• Principal Investigator: OGAWA Narihito 明治大学, 理工学部, 専任准教授 (50611109)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ラクトマイシン類 / カップリング反応 / 立体選択的合成

Outline of Final Research Achievements

Lactomycins are isolated from Streptomyces sp. ACT232. In this study, we synthesized lactomycins with the aim of structure-activity relationship (SAR) studies. After the reaction of optically active glycidol with 3-butyn-1-ol derivatives as starting material, the terminal hydroxy group was protected with dimethylvinylsilyl chloride. The silyl group was used to construct trisubstituted olefin by an intramolecular hydrosilylation reaction. The silyl group was converted to iodine, and the C3-C13 carbon chain was constructed by Suzuki-Miyaura coupling reaction of the borane in the C3-C7 part. Subsequently, an intramolecular lactonization reaction was used to construct the C1-C13 part.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

ラクトマイシン類はホスラクトマイシン類やロイストロダクシン類と類似の化学構造を持つため、タンパク質脱リン酸化酵素の一種であるプロテインホスファターゼ2A（PP2A）に対して阻害活性を示す可能性がある。また、ラクトマイシン類はホスラクトマイシン類よりも官能基が少ないため、簡便な合成法が開発できれば、様々な生物学的な研究や創薬研究へ展開しやすくなる。