Scalable Asymmetric Synthesis of MK-8998, a T-Type Calcium Channel Antagonist

J Org Chem. 2022 Feb 18;87(4):2120-2128. doi: 10.1021/acs.joc.1c01795. Epub 2021 Sep 28.

Abstract

Two scalable and efficient synthetic routes for the synthesis of a T-type calcium channel antagonist MK-8998 were developed from a simple pyridine building block. The key step to set the stereochemistry relied on either chiral rhodium catalyst-mediated asymmetric hydrogenation of an enamide or transamination of an arylketone that provided the corresponding product in high enantioselectivity and high yield.

MeSH terms

  • Amination
  • Calcium Channel Blockers* / pharmacology
  • Catalysis
  • Hydrogenation
  • Rhodium*
  • Stereoisomerism

Substances

  • Calcium Channel Blockers
  • Rhodium