Cyclol formation from tripeptides containing β-alanine

Abstract
Attempts to synthesize stable tetrahedral intermediates (cyclols) from β-alanine containing precursors are described. Cyclization of N-(N-benzyloxycarbonyl-β-alanyl)-Phe-Pro-ONp gave N-(N-benzyloxycarbonyl-β-alanyl)cyclo-(Phe-D-Pro). Cyclization of N-(N-benzyloxycarbonyl-Ala)-βAla-Pro-ONp and of N[N-(R)-(α-hydroxyisovaleryl)-βAla]-Pro-ONp afforded the corresponding anhydrocyclols. The first example of an oxa-cyclol related to a ten-membered cyclodepsitripeptide was synthesized by acylating cyclo-(βAla-Pro) with α-benzyloxypropionyl chloride followed by hydrogenolytic removal of the O-benzyl protecting group.

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