Azetidine-2-carboxylic acid structure

Our interest in the polyoxin group of antibiotics [50] was focused on the nature of polyoximic acid [51], a deceptively simple azetidine carboxylic acid derivative which had eluded the efforts of synthetic chemists [52] since the original publication of the structure. Only recently was a synthesis reported for /rnatural product based on low field NMR stupes [51]. A total synthesis of this acid in our laboratory [54,55], and comparison of NMR spectra with a sample kindly provided by Professor Isono showed that they were different. The sample of the naturally-derived amino acid was suitable for X-ray analysis (even after 20 years of isolation and storage ), and it proved to be ci5-polyoximic acid [54]. A new synthesis of this isomer was undertaken and confirmed its structural as well as stereochemical identity (Scheme 9) [55]. TTie stereochemical revision of polyoximic acid could... 

In addition to effects on biochemical reactions, the inhibitors may influence the permeability of the various cellular membranes and through physical and chemical effects may alter the structure of other subcellular structures such as proteins, nucleic acid, and spindle fibers. Unfortunately, few definite examples can be listed. The action of colchicine and podophyllin in interfering with cell division is well known. The effect of various lactones (coumarin, parasorbic acid, and protoanemonin) on mitotic activity was discussed above. Disturbances to cytoplasmic and vacuolar structure, and the morphology of mitochondria imposed by protoanemonin, were also mentioned. Interference with protein configuration and loss of biological activity was attributed to incorporation of azetidine-2-carboxylic acid into mung bean protein in place of proline. 

In addition to the 20 amino acids most frequently found in proteins a large group of amino acids occur in plants, bacteria, and animals that are not found in proteins. Some are found in peptide linkages in compounds that are important as cell wall or capsular structures in bacteria or as antibiotic substances produced by bacteria and fungi. Others are found as free amino acids in seeds and other plant structures. Some amino acids are never found in proteins. These nonprotein amino acids, numbering in the hundreds, include precursors of normal amino acids, such as homoserine and diaminopimelate intermediates in catabolic pathways, such as pipecolic acid d enantiomers of normal amino acids and amino acid analogs, such as azetidine-2-carboxylic acid and canavanine, that might be formed by unique pathways or by modification of normal amino acid biosynthetic pathways. 

Thus, diaziridine (5) is also named as a 2-hydrazipropane. A convenient short name for the N-N fragment of the diazirine cycle is azi (not to be confused with the similar abbreviations azy and azo for the residues of aziridine 2-carboxylic acid and azetidine 2-carboxylic acid, respectively <84YGK390>. The chemical structures of diaziridinone (6), diziridinimine (7), as well as fused diaziridine C—N bridged (8) and N—N bridged (9) (usually cis) systems are given. 

In another example, biodegradation of azetidine ring structures was investigated using the toxic, plant, natural product L-azetidine-2-carboxylic acid (ACA). ACA is made in large quantities by certain plants, such as Lily of the Valley, to ward off pathogens [26]. Despite this, some bacteria metabolize ACA productively (Fig. 3). Pseudomonas strain A2C was isolated from soil beneath Lily of the Valley plants and was able to grow on L-azetidine-... 

Figure 4.2 Structure of azetidine-2-carboxylic acid anhydride 12 and nicotianamine 13.

Certain changes in the proportion of different actinomycins synthesized by a given Streptomyces sp. may result from changes in the amino acid composition of the culture medium. Studies by Katz and Goss have indicated that addition to the medium of proline, hydrox5 roline, or sarcosine respectively may result in an increased synthesis of actinomycins with these particular residues at sites A and A, and that the addition of pipecolic acid or azetidine-2-carboxylic acid results in the production of new actinomycins in which residues of the added compounds occupy these sites. It seems that the peptide synthesizing mechanism does not distinguish perfectly, at sites A and A, between amino acids of similar structure. 

Kristensen I, Larsen PO (1974) Azetidine-2-carboxylic acid derivatives from seeds of Fagus silvatica L. and a revised structure for nicotianamine. Phytochemistry 13 2791-2798 Lloyd HA, Pales HM, Goldman ME, lerina DM, Plowman T, Schultes RE (1985) Brunfelsamidine a novel convulsant from the medicinal plant Brunfelsia grandiflora. Tetiahedron Lett 26 2623-2624... 

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