Lactams microbial hydroxylation

Although much of the work on the microbial hydroxylation of amides has been directed at active-site m ing of the enzyme responsible, the products themselves are valuable building blocks for further synthesis, for example, for various optically active sesquiteipenes or -lactams. In this latter context regioselective hydroxylation of unactivated positions is particularly attractive as several -lactam antibiotics, e.g. the carbapenem derivative thienamycin, have a free hydroxy group in their structure. 

After the discovery of the antibiotic thienamycin, compounds that contain tiie car-bapenem and penem ring systems have attracted much attention. The importance of stereochemistry of the hydroxyethyl group is demonstrated by the fact that this group must be in the R) configuration for antimicrobial activity to take place. Previously, synthesis of carbapenem and penum compounds have often utilized the optically active P-lactam intermediates [192-194]. Recently, d-(—)-3-hydroxybutyric acid prepared by the microbial hydroxylation of butyric acid has been used in the preparation of p-lactam [195,196]. 

Cephalosporins are -lactam antibiotics that block microbial cell wall synthesis. The original cephalosporin. Cephalosporin C, has only weak antibiotic activity. Therefore much more powerful second generation cephalosporins were developed by side-chain modification. Modifications at Cl are most effective but modifications at position 3 are also important so as to increase in vivo activity. Synthesis of the second generation cephalosporin cefuroxime requires the replacement of the C3 acetoxy side-chain of the precursor with a caibamate group. Chemical methods proceed via a hydroxylated intermediate which causes problems due to a tendency to lactonise at low pHs. Therefore development of a biocatalysis step was initiated in order to achieve selective reaction nnder mild conditions. 

---

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ , ]

See also in sourсe #XX -- [ , ]

See also in sourсe #XX -- [ ]

---