Total Synthesis of Yuzurine-type Alkaloid Daphgraciline
Lixuan Li, Long Min, Tian-Bing Yao, Shu-Xiao Ji, Chuang Qiao, Peilin Tian, Jianwei Sun, Chuang‐Chuang Li
Abstract
The first total synthesis of daphgraciline has been achieved, which also represents the first example of the synthesis of Daphniphyllum yuzurine-type alkaloids (∼50 members). The unique bridged azabicyclo[4.3.1] ring system in the yuzurine-type subfamily was efficiently and diastereoselectively assembled via a mild type II [5+2] cycloaddition for the first time. The compact tetracyclic [6–7–5–5] skeleton was installed efficiently via an intramolecular Diels–Alder reaction, followed by a benzilic acid-type rearrangement. The synthetically challenging spiro tetrahydropyran moiety in the final product was installed diastereoselectively via a TiIII-mediated reductive epoxide coupling reaction. Potential access to enantioenriched daphgraciline is presented.