New total synthesis of (+)-ambrein

The convergent synthesis of (+)-ambrein 1 was achieved based on a modified Julia coupling reaction between aldehyde 14 corresponding to the left-half A and sulfone 25a or 25b corresponding to the right-half B. Aldehyde 14 was synthesized in 14% overall yield (nine steps) from the enzymatic resolution product, epoxy alcohol (8aS)-2. Sulfone 25a or 25b was synthesized in 11 steps (25a: 41% overall yield, 25b: 56% overall yield) from the enzymatic resolution product, (1S,6S)-2,2-dimethyl-6-hydroxyhexane-1-carboxylate 4.

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(+)-AmbreinC30H52OEe = >99%[α]D24=+18.9 (c 0.47, EtOH)Source of chirality: lipaseAbsolute configuration: (1R,2R,4aS,8aS,1″S)