One-Pot Multi-Enzymatic Synthesis of the Four Stereoisomers of 4-Methylheptan-3-ol

Abstract

The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible stereoisomers of this compound were prepared from 4-methylhept-4-en-3-one by a one-pot procedure in which the two stereogenic centres were created during two sequential reductions catalysed by an ene-reductase (ER) and an alcohol dehydrogenase (ADH), respectively.

Biocatalytic Reduction Reactions from a Chemist's Perspective

“…Despite their simplicity, the combination of OYEs and ADHs, when both used in the reductive direction, allows for the formation of multiple stereoisomers depending on their enantioselectivity, as was recently demonstrated for the synthesis of all four stereoisomers of 4‐methylheptan‐3‐ol (Figure 9 a) [51] and the multiple stereoisomers of dihydrocarveol [52] …”

Discovery, Characterization, Engineering, and Applications of Ene-Reductases for Industrial Biocatalysis

“…In each step, one of two different enzyme variants was employed, which generated products of the opposite enantiomer. This enabled all 4 stereoisomers to be generated, which was advantageous given that each was active against a different species of beetle 66…”

Biokatalytische Reduktionen aus der Sicht eines Chemikers

“…[50] Werden beide Enzyme (OYE und ADH) in reduktiver Richtung verwendet lassen sich mehrere Stereozentren generieren. So konnten beispielsweise alle 4 Stereoisomere von 4-Methyl-3-heptanol (Abbildung 9 a) [51] oder mehrere Stereoisomere des Dihydrocarveols [52] erreicht werden.…”