Catalytic antibodies in synthesis: Design and synthesis of a hapten for application to the preparation of a scalemic pyrrolidine ring synthon for ptilomycalin A

被引:19
作者
Anderson, GT [1 ]
Alexander, MD [1 ]
Taylor, SD [1 ]
Smithrud, DB [1 ]
Benkovic, SJ [1 ]
Weinreb, SM [1 ]
机构
[1] PENN STATE UNIV,DEPT CHEM,UNIVERSITY PK,PA 16802
关键词
D O I
10.1021/jo951469t
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A catalytic antibody-based approach toward the synthesis of an optically active pyrrolidine ring synthon potentially useful for ptilomycalin A is described. Enantiomerically pure hapten 37 was designed and constructed with the eventual goal of generating antibodies for the enantioselective partial hydrolysis of a meso diester such as 44 into a monoacid 45. This transition state analog possesses a phosphonate group containing the requisite oxyanionic character of the tetrahedral intermediate for ester hydrolysis. A newly developed carbamate-based linker, which was found to be much more hydrolytically stable than the commonly used glutarate ester, was developed for coupling of the hapten to a carrier protein.
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页码:125 / 132
页数:8
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