A Novel 2H-Azirin-3-amine as a Dipeptide (Aib-Hyp) Synthon

Abstract

The synthesis of methyl (2S,4R)-4-(benzyloxy)-N-(2,2-dimethyl-2H-azirin-3-yl)prolinate (10), a novel 2H-azirin-3-amine ('3-amino-2H-azirine'), is described (Scheme 1). The reaction of methyl (2S,4R)-N-(2- methylpropanoyl)-4-(benzyloxy)prolinate (7) with Lawesson reagent gave methyl (2S,4R)-4-(benzyloxy)-N-[2-(methylthio)propanoyl]prolinate (8) and consecutive treatment with COCl2, 1,4-diazabicyclo[2.2.2]octane (DABCO), and NaN3 led to 10. The use of 10 as a building block of the dipeptide Aib-Hyp (Aib = 2- aminoisobutyric acid, Hyp = (2S,4R)-4-hydroxyproline) is demonstrated by the syntheses of several model peptides (Scheme 2 and Table). The benzyl protecting group of the 4-OH function in Hyp in the model peptides has been removed in good yields.