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DOI: 10.1055/a-2236-0413
An Improved and Scalable Synthesis of the Potent SREBP Inhibitor KK-052 via [3+2] Cycloaddition
This work was supported in part by Grants-in-Aid from the Japan Society for the Promotion of Science (No. 22K14688 to F.K. and No. 23K06029 to A.K.).
Abstract
KK-052 is a novel vitamin-D-based selective sterol regulatory element-binding protein (SREBP) suppressor that lacks vitamin D genomic activity mediated through the vitamin D receptor in both in vitro and in vivo settings. In our initial synthetic effort, KK-052 was produced as one of the structural isomers obtained via the Mitsunobu reaction involving a CD-ring allyl alcohol and 5-phenyl-1H-tetrazole. In this work, we present a refined methodology for enhancing the selective synthesis of KK-052 through a [3+2] cycloaddition between a CD-ring benzimidoyl chloride and sodium azide, a technique that proved amenable to gram-scale production. Additionally, this synthetic method permitted the production of a more potent m-methyl analogue of KK-052.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2236-0413.
- Supporting Information
Publication History
Received: 04 December 2023
Accepted after revision: 28 December 2023
Accepted Manuscript online:
28 December 2023
Article published online:
07 February 2024
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