Pd触媒によるアレン連続環化反応を利用したErgot Alkaloid骨格の一挙構築法開発と応用

抄録

Ergot alkaloids have been reported to exhibit broad biological activity. Several synthetic derivatives are used as important drugs (e.g., for Parkinson's disease). We investigated direct construction of the C/D ring system of ergot alkaloids based on palladium-catalyzed domino cyclization of amino allenes. Treatment of amino allene derivatives bearing a bromoindolyl group with Pd(PPh₃)₄ (5 mol%) and K₂CO₃ in DMF at 120 ^oC gave the desired tetracyclic indoles having the common core structure of ergot alkaloids in good yields. With this biscyclization as the key step, total synthesis of (+/-)-lysergic acid, (+/-)-lysergol and (+/-)-isolysergol was achieved. The proposed mechanism for biscyclization based on the stereochemical course of the reaction is also presented.