title: Total Synthesis of the Serine/Threonine-Specific Protein Phosphatase Inhibitor Tautomycin(1).
abstract: A convergent, asymmetric synthesis of the protein phosphatase inhibitor, tautomycin, is described. The natural product was constructed by joining two major fragments of comparable complexity at the C21-C22 bond. Absolute stereochemistry of the C1-C21 ketone originates from (S)-citronellene and (2R,3S)-geraniol epoxide. The anti stereochemical relationships at C6-C7 and C18-C19 were introduced with Duthaler's chiral titanium propionic enolate. Syn stereochemical relationships at C13-C14 and C23-C24 were established using an Evan's oxazolidinone chiral auxiliary. The spiroketal was efficiently constructed via a one-pot double-alkylation-spirocyclization sequence with acetone N,N-dimethylhydrazone serving as the central linchpin. Final coupling of the two halves using a chelation-controlled Mukaiyama aldol addition followed by deprotection yielded synthetic tautomycin that is identical to the natural product.
authors.affiliation: Department of Chemistry, University of California, Irvine, California 92717.
authors.forename: James E.
authors.initials: JE
authors.lastname: Sheppeck
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: A. Richard
authors.initials: AR
authors.lastname: Chamberlin