On the Electrophilicity of Cyclic Acylphosphoramidates (CAPAs) Postulated as Intermediates

Cyclic acylphosphoramidates (2-hydroxy-2-oxy-1,3,2-oxazaphospholidine-5-ones, CAPAs) are phosphate-activated amino acids possessing both a carboxyl-phosphoryl anhydride and a phosphoramidate bond in a ring. They structurally resemble NCAs (amino acid N-carboxyanhydrides, Leuchs' anhydrides), which have been extensively investigated. By contrast, the chemistry of CAPAs has remained almost unexplored since it was proposed in a prebiotic reaction of inorganic polyphosphates (Polyps) with amino acids. In the present work, the bielectrophilicity of alpha-CAPAs (Gly-CAPA, Ala-CAPA) was identified by isotopic analysis (O-18, N-15) and further proved by trapping alpha-CAPA with nucleophiles such as water, amino acids, phosphate and methanol in alkaline media, which yielded N-phosphoamino acids and peptide phosphoanhydride and phosphate ester derivatives. By comparison with the reactivity of NCAs, the bielectrophilicity of CAPAs indicates that CAPAs can provide rich chemistry. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weiriheim, Germany, 2009)