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Synthesis 2009(7): 1180-1184  
DOI: 10.1055/s-0028-1088013
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Synthesis of N-Protected α-Amino Acid Hydrazides

Mathieu Bibian, Sarah El-Habnouni, Jean Martinez, Jean-Alain Fehrentz*
Institut des Biomolécules Max Mousseron, UMR 5247, CNRS , Universités Montpellier 1 - Montpellier 2, Faculté de Pharmacie, B.P. 14491, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France
Fax: 33(4)67548654; e-Mail: jean-alain.fehrentz@univ-montp1.fr;
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Publication History

Received 30 October 2008
Publication Date:
16 March 2009 (online)

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Abstract

A new, mild, general, and efficient synthesis of N-protected α-amino acid hydrazides is described. This two-step preparation uses N-aminophthalimide as protected hydrazine to prepare N-protected α-amino acid hydrazide precursors, and subsequent de­phthaloylation with an aminomethyl polystyrene resin yields N-protected α-amino acid hydrazides. It has the advantages of avoiding the use of the toxic hydrazine reagent and being compatible with the most commonly used N-protecting groups. This strategy is particularly interesting in the case of N-(9-fluorenylmethoxycarbonyl)-protected amino acids. Within the limits of chiral HPLC detection, no epimerization is apparent.

Key words

amino acids - hydrazides - epimerization - protecting groups - aminomethyl resins

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Chiral HPLC: Chiracel OD column, 1 mL/min, hexane- i-PrOH, 80:20 with 0.1% TFA, monitoring at λ = 280 nm.