Prolines mercaptoacyl

Split synthesis of the library using four amino acids, four aldehydes, and five olefins in the presence of four mercaptoacyl chlorides (Scheme 3.110) generated the required proline library that was screened, after TEA cleavage of the products from the solid support, for inhibition of angiotensin converting enzyme ACE. 

E. M., Gallop, M. A. (1995) Combinatorial organic synthesis of highly functionalized pyrrolidines identification of a potent angiotensin converting enzyme inhibitor from a mercaptoacyl proline library. J Am Chem Soc 117, 7029-7030. 

MA Ondetti, A Miguel, J Krapcho. Mercaptoacyl derivatives of substituted prolines. U.S. Patent 4316906, 1982. 

Since functionalised prolines and proline analogues are frequently found as C-terminal residues in numerous ACE inhibitors. Gallop et al. used this solid-phase chemistry to generate a library of mercaptoacyl prolines. Thus the library was prepared by the split synthesis using four amino acids, four aldehydes, five olefins, and three mercaptoacyl chlorides as shown in Scheme 4.1.21. 

Scheme 1. The Affymax mercaptoacyl proline library 1.18 active against ACE. Direct comparison of iterative deconvolution and encoding protocols [19,21].

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