Stereoselective chemoenzymatic synthesis of sitophilate: a natural pheromone

The aggregation pheromone of the granary weevil Sitophilus granarius, (2S,3R)-1-ethylpropyl 3-hydroxy-2-methylpentanoate, has been synthesized in 63% total isolated yield and high chemical and enantiomeric purity (98% de, >99% ee) from readily available methyl 3-oxopentanoate. A stereoselective ketone reduction followed by an ester hydrolysis, were the two key steps of the synthesis and were both performed by commercially available enzymes.

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(2S,3R)-1-Ethylpropyl 3-hydroxy-2-methylpentanoateC11H22O3Ee = >99%[α]D25=-3.1 (c 1.7 CHCl3)Source of chirality: enzyme catalyzed asymmetric reductionAbsolute configuration: (2S,3R)