極めて安定な新規カンナビノイド生物学的等価体の不斉合成に成功～カンナビノイドの医薬的応用へ期待～

2025-03-07 早稲田大学

<関連情報>

• https://www.waseda.jp/inst/research/news/79953
• https://pubs.acs.org/doi/10.1021/jacs.4c18319

リガンドが制御する1,7-エニンの位置およびエナンチオ選択的[2 + 2 + 2]環化付加反応:ベンゾ[c]クロメン-1-オール骨格の構築とエナンチオ濃縮カンナビノールバイオアイソステアへのアクセス Ligand-Governed Regio- and Enantioselective [2 + 2 + 2] Cycloaddition of 1,7-Enynes: Assembly of the Benzo[c]chromen-1-ol Backbone and Access to Enantioenriched Cannabinol Bioisostere

King Hung Nigel Tang,Taichi Kishi,Natsuhiko Sugimura,Yuto Horio,and Takanori Shibata
Journal of the American Chemical  Published: February 5, 2025
DOI:https://doi.org/10.1021/jacs.4c18319

Abstract

We herein report a regioselective synthesis of the benzo[c]chromenol core via cationic rhodium-catalyzed [2 + 2 + 2] cycloaddition of 1,7-enynes with tetrolic acid derivatives. With the selection of an appropriate ligand, both regioisomers could be obtained in excellent regiomeric ratio and enantiomeric excess. The regioselectivity was governed by different factors, which was suggested by computational studies. Furthermore, the asymmetric synthesis of an axially chiral cannabinol bioisostere candidate was achieved by the transformation from central chirality to axial chirality. Demonstration of the synthesis of a natural compound was also depicted.