Stereoselective Synthesis of Steroidal Skeleton Having cis-fused C-D Ring System and Search for New Anticancer Compounds

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: University of Toyama
• Principal Investigator: Matsuya Yuji 富山大学, 学術研究部薬学・和漢系, 教授 (50255858)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オルトキノジメタン / 分子内Diels-Alder反応 / シスCD縮環型ステロイド骨格

Outline of Final Research Achievements

New method for construction of cis-fused steroidal skeleton was investigated using o-quinodimethane intermediate generated from thermal reaction of benzocyclobutene (BCB) derivatives. The substrate of this key reaction was successfully synthesized via aldol reaction between the BCB compound corresponding to A-ring and the aldehyde corresponding to D-ring. The thermal reaction of this substrate afforded the desired cis-fused steroidal compound.
In addition, oxidative synthetic routes for the D-ring structure of natural andrastins were investigated using a model substrate, and evaluation experiments of FTase inhibitory activity of the synthesized andrastin analogous compounds were also performed.

Free Research Field

有機化学

Academic Significance and Societal Importance of the Research Achievements

合成法があまり一般化されていない、シスCD縮環型ステロイド骨格を構築する有効な方法を示すことができた。また、同骨格を有し、抗癌性が期待される天然物アンドラスチン類の類縁化合物合成も行い、天然物を上回る活性化合物を見出したことから、本天然物に基づいた構造設計と化学合成が、新規な抗癌性化合物探索の有効なアプローチとなることが示された。