3-Azaspiro[5,5]undecan-2,4-dioxo-3-yl diphenyl phosphate (ASUD-diphenyl phosphate), a new reagent for the synthesis of the N-protected amino acid-ASUD ester

A new reagent, 3-azaspiro[5,5]undecan-2,4-dioxo-3-yl diphenyl phosphate (ASUD-diphenyl phosphate) is described for the synthesis of N-protected amino acid-ASUD esters which are active esters useful in the synthesis of peptides. This compound was synthesized by reacting N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione (HO-ASUD) with diphenyl chlorophosphate in the presence of a base at room temperature and was obtained in high yields. The ASUD-diphenyl phosphate reagent reacts with N-protected amino acids under mild conditions to give the corresponding ASUD active esters, while preserving the enantiomeric purity of the amino acid. The new reagent is a stable crystalline compound and eliminates the need for DCC, a potent skin allergen, used previously for the synthesis of N-protected amino acid-ASUD ester.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Methyl (tert-butoxycarbonyl)-l-phenylalanyl-l-phenylalaninateC24H30N2O5[α]D25 = −13.8 (c 1, CH3OH)Source of chirality: the precursorAbsolute configuration: L

tert-Butyl (R)-(1-(benzylamino)-3-methoxy-1-oxopropan-2-yl)carbamateC16H24N2O4[α]D25 = −20.8 (c 0.9, CHCl3)Source of chirality: the precursorAbsolute configuration: (R)

(R)-2-Acetamido-N-benzyl-3-methoxypropanamideC13H18N2O3[α]D25 = +16.0 (c 1, CH3OH)Source of chirality: the precursorAbsolute configuration: (R)