Chemistry Reference
In-Depth Information
in the Sharpless epoxidation as a tool for industrial organic synthesis increased substantially after Sharpless
et al.
discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically
pure titanium-tartrate complex simply by adding molecular sieves to the epoxidation reaction mixture [66].
Using this practical and reproducible catalytic variant, an industrial process for ton-scale productions of (
S
)- and (
R
)-
glycidol and (
S
)- and (
R
)-methylglycidol has been developed. These low-molecular weight epoxy alcohols are
versatile building blocks for the synthesis of a number of chiral molecules.
As far as drug synthesis is concerned, one of the most significant applications of the Sharpless method amongst the
innumerable ones found in the past 20 years is the routine preparation (Fig.
13
) of antipodal pairs of known chirality
of -blockers such as propranolol [67].
Enzymatic Methods
Biocatalysis or biotransformation encompasses the use of biological systems, whether whole cells, cellular extracts
or isolated enzymes, to catalyze the conversion of one compound to another. The potential of microorganisms and
enzymes for the transformation of synthetic compounds with high chemo-, regio- and enantioselectivities has been
demonstrated.
For thousands of years, mankind has used biological processes in an empirical way, e.g., to produce alcoholic
beverages, bread, fermented foods and dairy products. Thanks to the investigations by Louis Pasteur and Robert
Koch in the second half of the 19
th
century, we learned that these processes are in fact catalyzed by micro-organisms
or by microbial enzymes, respectively. This knowledge opened the way for the more rational development of new
microbial and enzymatic processes in the food and dairy sector and in the chemical and pharmaceutical industries.
Early denominations of this new approach were “Zymotechnology” or “Technical Biology”.
The term “Biotechnology” was first used in the year 1917. In these early times of industrial biotechnology, the
leading representatives of the new science were already promoting the idea of using biological systems to create
more efficient, more selective, and environmentally friendlier processes for the conversion of raw materials into
industrial products, thereby substituting problematic chemical transformations. The concept of a more sustainable
use of the limited resources was thus one of the driving forces for the political vision of sustainable development
promoted by national and international conferences and organizations.
A report published by the OECD [68] analyzes the state of the art and the future development needs for industrial
biotechnology. Some important conclusions in this report summarizing the state of the art are:
Biotechnological operations are currently used in a wide range of major industrial processes.
Economic competitiveness has been established for a variety of biotechnological applications to
achieve cleanliness.
Biotechnology-based processes have been successfully integrated into large-scale operations.
Industrial penetration of biotechnology is increasing as a consequence of advances in recombinant
DNA technologies.
Biotechnological operations have led to cleaner processes with lowered production of wastes and in
some cases lower energy consumption.
The fine chemicals industry is one of the industrial segments where the impact of biotechnology is felt
most strongly.
Preparation of L-DOPA by an Enzymatic Process
L-DOPA, a metabolic precursor of dopamine, is a very important drug for the treatment of parkinsonism. A very
interesting industrialized bioprocess is the production of L-DOPA using -tyrosinase (tyrosine phenol lyase) in a
resting cell system. This enzyme catalyzes a variety of reactions: -elimination (I), -replacement (II) and the
reverse of -elimination (III) (R, R' = phenyl-, hydroxyphenyl-, dihydroxyphenyl-, trihydroxyphenyl-).
