Studies on conformationally restricted, disiloxane bridged analogues of the enkephalins
Abstract
Solution-phase synthesis of protected [Ser2, Ser5]- and [D-Ser2, Ser5]-enkephalins, followed by treatment with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane [Pri2Si(Cl)–O–Si(Cl)Pri2] in base have yielded cyclic bridged disiloxane analogues showing biological activity in an in vitro assay. Highfield 1H n.m.r. studies augmented by n.O.e. difference spectroscopy, temperature dependence studies of the amide protons, and the use of computer graphics support the presence of a 2→5 H-bonded β-bend conformation for the most biologically potent of the cyclic analogues.