American Chemical Society
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Total Synthesis of the Cytotoxic Threo, Trans, Erythro, Cis, Threo Annonaceous Acetogenin Trilobin

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journal contribution
posted on 1999-01-15, 00:00 authored by James A. Marshall, Hongjian Jiang
A synthesis of trilobin, a new stereochemical varient of the adjacent bis-tetrahydrofuran subgroup of the Annonaceous acetogenins, is described. The synthesis involves three stereochemically defining carbon−carbon bond-forming steps. The first of these introduces the C23−C24 stereocenters and the left side chain by means of an SE2‘ addition of the nonracemic 11-carbon γ-oxygenated allylic indium reagent derived from the α-oxygenated allylic stannane 4 to a C24−C16 core aldehyde 3. The second develops the C15−C16 stereocenters and a segment of the right chain through BF3-promoted SE2‘ addition of the nonracemic 6-carbon γ-oxygenated allylic stannane 11 to the C16−C34 aldehyde 10. The third employs the addition of the dialkylzinc reagent 17 to the C10−C34 aldehyde 15 in the presence of a chiral bis-sulfonamide catalyst to establish the C10 stereocenter while adding the C1−C9 residue of the right chain. The C36 stereocenter and the butenolide are appended through condensation of the C1−C34 ester with the protected (S)-lactaldehyde 23.