Glutamic acid monoesters

General synthetic methods of preparation pf a-monoesters and a-mono-amides of MTX were also described by Piper et al. [240], The key intermediate in their scheme was 2,4-diamino-6-bromomethylpteridine, which could be condensed, for example, with a-methyl V-[4-(V-methylamino)ben-zoyl]-L-glutamate or A -[4-(V-methylamino)benzoyl]-L-glutamic acid a-amide... 

The synthesis of monoesters based on perfluorinated alcohols and aspartic or glutamic acid has been reported, and the corresponding betaines (24) have been prepared (Scheme 21). The yields for these reactions are universally poor, however [15]. 

Likewise the acid or base catalyzed reaction of an alcohol and an acid anhydride is a regular method of esterification [4]. For many acids the most convenient experimental procedure is to form a mixed anhydride in situ by reaction with trifluoroacetic anhydride [23, 24] or the reagents listed above (method A). Cyclic anhydrides of dibasic acids yield monoesters with alcohols and this reaction is utilized in the preparation of glutamine (11) from glutamic acid (10) and in a similar synthesis of asparagine [35, 36]. 

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