Syntheses of Bufospirostenin A and Ophiopogonol A by a Conformation-Controlled Transannular Prins Cyclization
Peicheng Yang1,2, Yan-Yu Li3, Hailong Tian2
1Shanghai Frontiers Science Center for TCM Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
Abstract:
Controlling the conformation of medium-sized rings is challenging because of their flexibility and ring strain effects. Herein, we report non-Curtin-Hammett conditions for the precise control of the conformation of cyclodecenones to effect the first cis-selective transannular Prins cyclization, which enabled concise syntheses of the 5(10→1)abeo-steroids bufospirostenin A and ophiopogonol A in only seven steps from inexpensive starting materials. Computational results indicated that the key cyclization was kinetically controlled and proceeded via either a Prins pathway or a carbonyl-ene pathway, depending on the reaction conditions. Moreover, conformational isomerization played a critical role in determining the stereochemistry of the products.
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