Convenient Preparations of Chiral N,N'-Ethylene-Bridged Dipeptides and Their Uses as Units of Pseudopeptides.

Several workers have synthesized chiral and achiral N, N'-ethylene-bridged dipeptides (piperazin-2-one derivatives), and used them mainly as units of biologically active pseudopeptides such i : as enkephalin analogs because these structurally constrained and lipophilic dipeptides afford the character resisting enzymatic hydrolysis to biologically active peptides. However, their synthetic methods have some problems (nonstereoselective, multi-steps, troublesome techniques, expensive reagents etc.) Therefore; we have developed more convenient procedures for preparing N, N'-ethylene-bridged dipeptides. This article reports four kinds of synthetic methods of chiral N, N'-ethylene-bridged dipeptides, in which various (R) or (S) -α-amino acids are used as starting materials. Moreover, a series of studies on the structures and the functionalities (enantioselective inclusion and transport of (R) - and (S) -ammonium salts, complexing of metal ions) of macrocyclic pseudopeptides and on the enkephalin- and dermorphin-like biological activities of linear pseudopeptides containing these dipeptides as their units are introduced and discussed. Also, the synthesis of a macrocyclic polyamine obtained by the BH3 reduction of macrocyclic pseudopeptide and the structure of its metal complex ion are described.