Amino acid pathway cyclization

The principal pathway for the decomposition of aspartame begins with the cleavage of the ester bond, which may or may not be accompanied by cyclization (Eig. 2). The resultant diketopipera2ine and/or dipeptide can be further hydroly2ed into individual amino acids (qv). 

A more complex pathway of activation is seen in N-amino acid derivative of phosphoramidic acid diesters of antiviral nucleosides, as exemplified by prodrugs of stavudine (9.79, Fig. 9.14) [153 -155], The activation begins with a carboxylesterase-mediated hydrolysis of the terminal carboxylate. This is followed by a spontaneous nucleophilic cyclization-elimination, which forms a mixed-anhydride pentacycle (9.80, Fig. 9.14). The latter hydrolyzes spontaneously and rapidly to the corresponding phosphoramidic acid monoester (9.81, Fig. 9.14), which can then be processed by phosphodiesterase to the nucleoside 5 -monophosphate, and by possible further hydrolysis to the nucleoside. 

The library synthetic pathway is depicted, where the dendritic structure shown in Figure 7.24 is simplified as a single functional site rather than the actual eight carried by the dendritic core. Coupling with a protected amino acid (A, I, or F, first monomer set) and deprotection produced a resin bound amine which was amidated with y- or <5-ketoacids (second monomer set) and finally cyclized with substituted phenylhydrazines (third monomer set) to give the dendrimer bound indoles. These were cleaved by heating at 50°C with methanolic triethylamine, producing the pure library pools in solution (total yield >60%, HPLC purity >85%). 

The isolation of alkaloids bearing the 8-hydroxyquinoline moiety prompted postulation (17) of a biosynthetic pathway to 1 from the amino acid tryptophan, for which chemical analogies are known (22) (Scheme 2). It should be noted, however, that, in general, quinolines are biosynthesized from anthranilic acid (14). Biosynthesis of broussonetine (4) would involve condensation of two molecules of 1 with a molecule of acetyl-CoA followed by cyclization, as depicted in Scheme 3. 

Oxazolidin-5-one Intermediates. Several workers have demonstrated the significance of an inframolecular cyclization (Scheme 8) in the Schiff base form of aldosyl-a-amino acids, as an intermediate step of the Amadori rearrangement, which is accompanied by decarboxylation of the amino acid. One important example of the reaction is a pathway for acrylamide formation from D-glucose and L-asparagine in fried foods, such as potatoes. 

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