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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Asymmetric Synthesis of Triazole Antifungal Agents Enabled by an Upgraded Strategy for the Key Epoxide Intermediate
Yu Tang1, Zhuo Li1, Meiqi Zeng1
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China.
Abstract:
A streamlined and efficient approach to the key epoxide intermediate for the asymmetric synthesis of triazole antifungal agents is presented. This synthesis highlights a P(NMe2)3-mediated nonylidic olefination of α-keto ester, ensuring the exclusive formation of the requisite (Z)-alkene, followed by a highly enantioselective Jacobsen epoxidation to establish the two vicinal stereocenters in a single step. The versatility of this strategy is exemplified through the efficient synthesis of efinaconazole and ravuconazole.
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