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. 2022 May 6;87(9):6499-6503.
doi: 10.1021/acs.joc.2c00427. Epub 2022 Apr 20.

Chemoenzymatic Synthesis of the Most Pleasant Stereoisomer of Jessemal

Silvia Venturi  1 , Milos Trajkovic  2 , Danilo Colombo  1 , Elisabetta Brenna  1 , Marco W Fraaije  2 , Francesco G Gatti  1 , Piero Macchi  1 , Emilio Zamboni  1
Affiliations

Chemoenzymatic Synthesis of the Most Pleasant Stereoisomer of Jessemal

Silvia Venturi et al. J Org Chem. .

Abstract

We describe the asymmetric synthesis of the most pleasant enantiomer of Jessemal fragrance. The key steps are (i) the one-pot reduction of an α-chloro-tetrasubstituted cyclohexenone to give the chlorohydrin, catalyzed by two stereoselective redox enzymes (an ene-reductase and an alcohol dehydrogenase); (ii) the regioselective epoxide ring-opening with organocuprate or organolithium nucleophiles. Density functional theory calculations together with the Curtin-Hammett principle allowed the rationalization of the regioselectivity.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Retrosynthesis of Jessemal. (B) One-pot multienzymatic stereoselective reduction of α-chloro cycloenones.
Scheme 1
Scheme 1. (A) Synthesis of Jessemal; (B) C(4) Regioselective Ring-Opening of an Unsubstituted Tetrahydropyranyl Epoxide with Carbon Nucleophiles Reported by Crotti et al.
Scheme 2
Scheme 2. (A) Ring-Opening with Different Nucleophiles; (B) Fürst-Plattner Regiospecificity for the BnNH2 Addition
Figure 2
Figure 2
Energy paths for the BF3 promoted organolithium ring-opening at 195 K. For clarity, THF structures and H atoms are omitted.
See this image and copyright information in PMC

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