Directed Biosynthesis of Mitragynine Stereoisomers

Carsten Schotte(Max Planck Institute for Chemical Ecology), Yindi Jiang(Max Planck Institute for Chemical Ecology), Dagny Grzech(Max Planck Institute for Chemical Ecology), Thu‐Thuy T. Dang(Max Planck Institute for Chemical Ecology), Larissa C. Laforest(University of Florida), Francisco León(University of Florida), Marco Mottinelli(University of Florida), Satya Swathi Nadakuduti(University of Florida), Christopher R. McCurdy(University of Florida), Sarah E. O’Connor(Max Planck Institute for Chemical Ecology)
Journal of the American Chemical Society
February 22, 2023
Cited by 67Open Access
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Abstract

("kratom") is used as a natural remedy for pain and management of opioid dependence. The pharmacological properties of kratom have been linked to a complex mixture of monoterpene indole alkaloids, most notably mitragynine. Here, we report the central biosynthetic steps responsible for the scaffold formation of mitragynine and related corynanthe-type alkaloids. We illuminate the mechanistic basis by which the key stereogenic center of this scaffold is formed. These discoveries were leveraged for the enzymatic production of mitragynine, the C-20 epimer speciogynine, and fluorinated analogues.


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