On the synthesis of N-maleoyl amino acids in aqueous media: cautionary tales for the unwary traveller

Michael John Paterson,Aleksandar Jovanovic

doi:10.3998/ark.5550190.0011.a02

Abstract

The high cost or protracted syntheses associated with N-maleoyl amino acid derivatives coupled with a considerable demand from both the life and physical sciences has spurred the search for facile, low-cost routes to these compounds. Herein, we demonstrate that a recently published method purporting to deliver N-maleoyl amino acids by cyclization of maleamic acids in water, instead results in a hydrolysis product, namely the corresponding hemi-maleate salt.

Highlights

There is a considerable demand for low-cost, high purity N-maleoyl amino acids (NMAAs) for use in such diverse pursuits as the preparation of polymers,[1] the elaboration of metal surfaces[2] and the synthesis of bioconjugates.[3]
The widespread use of NMAA active esters as heterobifunctional crosslinkers has resulted in the development of a number of methods[4] for their rapid preparation; for applications requiring the free acids the synthetic options are less appealing
The traditional methods used to prepare NMAAs are limited in their utility by either a lack of scalability,[5] that they are cumbersome from a practical perspective,[6] or that they require a protracted synthesis.[7]

Summary

Introduction

There is a considerable demand for low-cost, high purity N-maleoyl amino acids (NMAAs) for use in such diverse pursuits as the preparation of polymers,[1] the elaboration of metal surfaces[2] and the synthesis of bioconjugates.[3]. Preparation and attempted cyclization using the Song methodology i) Method A acetic acid 8 h ii) Method B water 4 h.

Results

Conclusion