A superior synthesis of aspartame

✍ Scribed by Fredric J. Vinick; Stanley Jung

• Book ID: 104220591
• Publisher: Elsevier Science
• Year: 1982
• Tongue: French
• Weight: 185 KB
• Volume: 23
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)87092-6

✦ Synopsis

The dlpeptlde sweetener, aspartame, has been prepared In high yield via the coupling of L-phenylalanlne methyl ester and L-aspartlc acid N-thlocarboxyanhydrrde.

The novel dipeptlde sweetener, aspartame,* I, was first synthesrzed In 1966.' Since that time considerable effort has been devoted to dlacoverlng a short, highly efficient route to thrs unique substance.

HO cpc~"

2 CO2CH3

In order to synthesize aspartame effectively one must overcome the inherent dlfflculty of achieving reglospeclfrc reactlvlty at the a-carboxyl group of aspartlc acid, 2.

Two partrcularly lngenrous solutions to this problem have been reported. Pletsch' utilized B-lactam 2 as a means of protecting the aspartyl f3-carboxyl group; Isowa and Oyama* were able to couple N-carbobenzoxy-L-aspartlc acid exclusively at the a-positron, employing the enzyme, thermolysm, as a catalyst.

2

The most commonly used approach to aspartame has, however, involved ring openrng of an aspartlc anhydrlde, e.g., 4a_c.