Synthesis of a C1-C21 subunit of the protein phosphatase inhibitor tautomycin: A formal total synthesis

被引:52
作者
Marshall, JA [1 ]
Yanik, MM [1 ]
机构
[1] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA
关键词
D O I
10.1021/jo0056951
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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)(2)-C=O, 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.
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收藏
页码:1373 / 1379
页数:7
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