Portal de Periódicos da CAPES

Synthesis of a C1−C21 Subunit of the Protein Phosphatase Inhibitor Tautomycin: A Formal Total Synthesis

2001; American Chemical Society; Volume: 66; Issue: 4 Linguagem: Inglês

10.1021/jo0056951

1520-6904

James A. Marshall, Mathew M. Yanik,

Marine Sponges and Natural Products

The synthesis of a C1−C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2CO, to afford an intermediate ketone which is converted to the core spiroketal moiety of tautomycin upon acid treatment. Chain elongation by another addition of the aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high diastereoselectivity to install the remaining stereocenters. The resulting homopropargylic alcohol adduct is converted to a methyl ketone through intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived five-membered siloxane. This ketone proved identical to an intermediate employed by Chamberlin in a prior total synthesis of tautomycin.