7 - Aminodeacetoxycephalosporanic acid

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). 

Scheme 6.20 One-pot conversion of phenylglycine nitrile and 7-aminodeacetoxycephalosporanic acid to cephalexin.

Since amides are often used as acyl donors in the enantioselective acylation of amines, a combination of a NHase and an amidase could, in principle, be used for the direct acylation of an amine by the nitrile precursor of the amide. An example of such a one-pot reaction is shown in Scheme 6.20. The (R)-enantiomer of phenylglycine nitrile undergoes NHase-catalyzed conversion to the corresponding (R)-amide and the latter reacts in situ with 7-aminodeacetoxycephalosporanic acid, in the presence of penidlhn amidase, to afford the cephalosporin antibiotic, cephalexin [39]. 

The enzymatic synthesis of P-lactam antibiotics from P-lactam nuclei 6-aminope-nicillanic acid (APA) and 7-aminodeacetoxycephalosporanic acid (ADCA) and appropriate side chain donors has been largely studied [75, 76]. 

The manufacture of several semisynthetic oral cephalosporin antibiotics involves the chemical ring expansion of penicillin V to 7-aminodeacetoxycephalosporanic acid (7-ADCA Fig. 2 [68]). This is a costly and potentially environmentally damaging process [69], Cloning of the C. acremonium cefEF gene (DAOCS/ DACS [47]) and the S. clavuligerus cefD (IPNE) and cefE gene (DAOCS [43]) opened the possibility for biosynthetic/enzymatic processes for production of 7-ADCA. 

In the very important therapeutic class of antibiotics, both 6-AP A (6-amino-penicillinic acid) and 7-ADC A (7-aminodeacetoxycephalosporanic acid) are being produced today on multi-ton scale using the cross-linked crystal form of peni-cillin-G amidase (SynthaCLEC -PA) (P. Lanciano, President, Altus Biologies,... 

A/-(Phenylacetyl)-7- aminodeacetoxycephalosporanic acid 7-Phenylacetamidodeacetoxy-cephalosporanic acid C16H16N2O4S 27266-72-7 332.374 cry(2-Pr0H/ 200 peth) ... 

An important industrial process using peracetic acid for sulphoxide formation is that of 7-ADCA (7-aminodeacetoxycephalosporanic acid, a cephalosporin antibiotic precursor) production, in which penicillin is oxidised to sulphoxide followed by ring-expansion [218] (Figure 9.11). 

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