Chemistry Reference
In-Depth Information
Scheme 14.23
Fig. 14.10
Biochemical approaches to
industrial antibiotics.
efficiency, a route needs to include a recycle step for
the non-hydrolysed product, otherwise the final
yield is limited to 50% (Scheme 14.23).
Lipase-based asymmetric esterifications of profens
[142] has been used industrially for the synthesis of
profen-based prodrugs because of the known gas-
trointestinal side effects that occur upon administra-
tion of the pure acid. Derivatisation of the acid as an
ester lowers these side effects by allowing the ester
hydrolysis to occur
in vivo
. Under these conditions,
one enantiomer of racemic ibuprofen is esterified by
Rhizomucor miehei
lipase in enantiomeric excesses as
high as 97%. In the case of the profens, many dif-
ferent types of prodrugs have been suggested and
could be produced by similar technology [143].
One of the largest pharmaceutical uses for biopro-
cessing is in the production of semi-synthetic peni-
cillins and cephalosporins. Key starting materials in
this industry include the fermentatively produced
penicillins G and V and cephalosporin C. New ana-
logues are prepared by the enzymatic deacylation of
the starting material to give 6-aminopenicillanic acid
or 7-aminocephalosporanic acid [144]. Semi-
synthetic antibiotics are formed by reaction of the
free amine with different acylating agents. Forma-
tion of 7-ACA is a step in the manufacture of the
commercial antibiotic Ceflaclor (Fig. 14.10).
6 Conclusions
The chemical industry is becoming more sensitised
to the perception of black and red manufacturing
and its effect on the environment and society. In
recent years, the industry has been working to
address these issues, especially as a compelling case
is being made that a green approach also can be a
profitable approach. The impact of green technology
will be felt gradually as greater numbers of processes
are improved. Catalysis has earned the right to be
included as a key component of atom-economical
low-waste manufacturing, and will continue to lead
the drive to streamline multistep industrial process.
