Catalytic asymmetric synthesis of (S,4E,15Z)-docosa-4,15-dien-1-yn-3-ol, an antitumor marine natural product

An efficient enantioselective total synthesis of an antitumor marine natural product (S,4E,15Z)-docosa-4,15-dien-1-yn-3-ol 1 with 96% ee and 15% overall yield has been achieved; this is the first preparation of 1 via asymmetric catalytic strategy. The key steps involve the asymmetric addition of trimethylsilylacetylene to a diolefinc aldehyde using a (R,R)-ProPhenol ligand and a zipper reaction of an alkyne.

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(S,4E,15Z)-Docosa-4,15-dien-1-yn-3-olC22H38OEe = 96%[α]D20 = +18.4 (c 0.10, MeOH)Source of chirality: (R,R)-ProPhenolAbsolute configuration: (S)