3- Aminonocardicinic acid

The methodology provides a synthesis of 3-aminonocardicinic acid (1), from p-hydroxyphenylglycine.2... 

Aminonocardicinic acid, 233 Ancepsenolide, 74 Antheridium-inducing factor, 259 Anthracyclines and derivatives, 71, 156,... 

A recent synthesis of 3-aminonocardicinic acid (3, the nucleus of nocardicins, antibiotics from actinomycetes) involved this cyclization of a /3-halopropionamide. Thus treatment of 1 with NaH in dilute solution (DMF-CH2CI2) led to the /3-lactam... 

Townsend, C. A., Nguyen, L. T. Improved asymmetric synthesis of (-)-3-aminonocardicinic acid and further observations of the Mitsunobu reaction for -lactam formation in seryl peptides. Tetrahedron Lett. 1982, 23,4859-4862. 

In a series of papers [54-56], Palomo reported work leading to C-4-unsubstituted P-lactams including 3-aminonocardicinic acid. The cis. trans ratio of products of the ketene-imine cycloaddition was shown to be dependent on the bulk of the substituents in these groups. Thus while imine 78 gave an equimolar ratio of cis and trans azetidinones 79, use of the 2-methylcinnamaldehyde-derived imine 80 afforded only the c/5-compound 81. A useful method was... 

Total syntheses of nocardicin A and D have been reported. The important stage is the preparation of 3-aminonocardicinic acid from 4-hydroxyphenylglycine via an acid chloride-imine reaction (Scheme 128). ... 

The nocardicin nucleus 3-aminonocardicinic acid (3-ANA) (7) has not been found in nature, but can be prepared by deacylation of nocardicin C using microbial amidases 10). The first chemical method leading to (7) involved acid treatment of the bisthiourea derivative (8) of nocardicin C 11). A more recent method 12) makes use of the reaction of the oxime grouping of nocardicin A with di-/-butyl dicarbonate. This results in (9) which on treatment with trifluoroacetic acid gives (7). Further confirmation of the structure and stereochemistry of the nocardicins was the identification of the acylamino-derivative (10) derived from 3-ANA, with a compound obtained by partial synthesis from penicillin G 11). Another semi-synthetic approach (75) to the nocardicins from penicillin is by way of the thiazoline (11), the final step being Raney nickel desulphurisation of (12). 

Kamori, T., K. Kunigita, K. Nakahara, H. Aoki, and H. Imanaka Production of 3-Aminonocardicinic Acid from Nocardicin C by Microbial Enzymes. Agric. Biol. Chem. 42, 1439 (1978). 

Mattingly, P. G., and M. J. Miller Synthesis of 2-Azetidinones from Serine-hydroxamates Approaches to the Synthesis of 3-Aminonocardicinic Acid. J. Org. Chem. 46, 1557 (1981). 

In a similar way, several cephalosporins have been hydrolyzed to 7-aminodeacetoxycephalosporanic acid (72), and nocardicin C to 6-aminonocardicinic acid (73). Penicillin G amidase from Pscherichia coli has been used in an efficient resolution of a racemic cis intermediate required for a preparation of the synthon required for synthesis of the antibiotic Loracarbef (74). The racemic intermediate (21) underwent selective acylation to yield the cis derivative (22) in 44% yield the product displayed a 97% enantiomeric excess (ee). 

Nocardicin C 3-Aminonocardicinic and a-aminoadipic acids Pseudomonas schuyikilliensis... 

A novel synthesis of nocardicins from hexahydro-2-triazines has been reported/ The strategy behind this synthesis lies in the expectation that treatment of hexahydro-s-triazines with a Lewis acid should give formaldimines which on reaction with an acid chloride would yield monocyclic jS-lactams. This was realized in practice with the hexahydro-s-triazines derived from a-amino-acids, e.g. Scheme 95. The 3-aminonocardicin nucleus is readily available by application of the usual deprotection procedures. 

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