Generation of quaternary stereocenters via ene-reductase mediated desymmetrization of cyclohexadienones

Description

Molecules containing quaternary stereocenters often show interesting biological activities. However, the stereoselective assembly of such molecules still represents a challenging task in organic chemistry, especially when the quaternary stereocenter in question shall be formed in a remote position from a functional handle such as a carbonyl group. One solution to this problem is the desymmetrization of cyclohexadienones. This strategy allows the establishment of a quaternary stereocenter in γ-position to the carbonyl moiety.
Previously, this strategy has been demonstrated for metal hydride catalyzed systems.2,3 Due to our ongoing interest in the field of non-natural ene-reductase catalyzed biotransformations,4 we established a yet unpublished ene-reductase mediated desymmetrization of cyclohexadienones. The investigated ene-reductases (OPR3 and YqjM) are able to perform these transformations in >99% ee. Furthermore, overreduction to the fully saturated cyclohexanones is observed only in small amounts, even when the biotransformations are carried out with as much as two equivalents of NADH cofactor. In summary, our biocatalytic system allows the formation of cyclohexenones equipped with a quaternary stereocenter in nearly enantiopure form. The products itself bear the potential of diverse follow up chemistry, without erosion of enantiopurity.

Period	16 Jul 2023 → 21 Jul 2023
Event title	Gordon Research Conference: 2023 Enzymes, Coenzymes and Metabolic Pathways
Event type	Conference
Location	Waterville Valley, United States, New HampshireShow on map
Degree of Recognition	International