A concise and stereoselective chemoenzymatic synthesis of Sitophilate, the male-produced aggregation pheromone of Sitophilus granarius (L.)

(2S,3R)-Sitophilate, the male-produced aggregation pheromone of the granary weevil Sitophilus granarius (L.) was prepared stereoselectively using a novel chemoenzymatic approach in 50% overall yield. The synthetic design was based on an enantioselective fungal reduction of ethyl 2-methyl-3-oxopentanoate with a strain of Aureobasidium pullulans (CCM H1), followed by a Mitsunobu inversion at C3. The last step in the synthetic sequence was a lipase-mediated transesterification using the commercially available Candida antarctica B lipase (CaL B, Novozym 435) using microwave irradiation under solvent-free conditions.

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(2S,3R)-Ethyl 3-hydroxy-2-methylpentanoateC8H16O3ee = >99%[α]D25=+15.0 (c 2.8, MeOH)Source of chirality: enzymatic reduction (Aureobasillium pullulans) and further Mitsunobu reactionAbsolute configuration: (2S,3R)

(2S,3R)-Pentan-3-yl 3-hydroxy-2-methylpentanoateC11H22O3ee = >99%[α]D22=-5.4 (c 1.0, AcOEt)Source of chirality: enzymatic reduction (Aureobasillium pullulans) and further Mitsunobu reactionAbsolute configuration: (2S,3R)