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 α‐CAPAs (Gly‐CAPA, Ala‐CAPA) was identified by isotopic analysis ( 18 O, 15 N) and further proved by trapping α‐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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)