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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Diastereoselective total synthesis of (±)-schindilactone A, Part 1: Construction of the ABC and FGH ring systems and
Tian-Wen Sun1, Wei-Wu Ren, Qing Xiao
1Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Science and Peking-Tsinghua Center for Life Sciences, College of Chemistry of Peking University, 202 Chengfu Road, Beijing 100871, China.
Abstract:
First-generation synthetic strategies for the diastereoselective total synthesis of schindilactone A (1) are presented and methods for the synthesis of the ABC, FGH, and CDEF moieties are explored. We have established a method for the synthesis of the ABC moiety, which included both a Diels-Alder reaction and a ring-closing metathesis as the key steps. We have also developed a method for the synthesis of the FGH moiety, which involved the use of a Pauson-Khand reaction and a carbonylative annulation reaction as the key steps. Furthermore, we have achieved the construction of the central 7-8 bicyclic ring system by using a [3,3]-rearrangement as the key step. However, unfortunately, when this rearrangement reaction was applied to the construction of the more advanced CDEF moiety, the anticipated annulation reaction did not occur and the development of an alternative synthetic strategy would be required for the construction of this central core.
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