ABSTRACT
Key Words: Biocatalysis; chiral intermediates; enzymatic processes; synthesis of pharmaceuticals.
The production of single enantiomers of chiral intermediates has become increasingly important in the pharmaceutical industry [1]. Single enantiomers can be produced by chemical or chemoenzymatic synthesis. The advantages of biocatalysis over chemical synthesis are that enzyme-catalyzed reactions are often highly enantioselective and regioselective. They can be carried out at ambient temperature and atmospheric pressure, thus avoiding the use of more extreme conditions, which could cause problems with isomerization, racemization, epimerization, and rearrangement. Microbial cells and enzymes derived therefrom can be immobilized and reused for many cycles. In addition, enzymes can be overexpressed to make biocatalytic processes economically efcient, and enzymes with modied activity can be tailor made. Directed evolution of biocatalysts can lead to increased enzyme activity, selectivity, and stability [2-10]. A number of review articles [11-21] have been published on the use of enzymes in organic synthesis. This review provides
16.11 Tryptase Inhibitors...................................................................................... 233 16.11.1 Enzymatic Preparation of (S)-N(tert-Butoxycarbonyl)-3-
Hydroxymethyl Piperidine ........................................................... 233 16.12 Anticholesterol Drugs: Hydroxymethyl Glutaryl CoA Reductase
Inhibitors .....................................................................................................234 16.12.1 Preparation of (S)-4-Chloro-3-Hydroxybutanoic Acid Methyl
Ester .............................................................................................234 16.12.2 Enzymatic Reduction of 3,5-Dioxo-6-(Benzyloxy) Hexanoic
Acid, Ethyl Ester .......................................................................... 235 16.13 Anti-Alzheimer’s Drugs ............................................................................. 235
16.13.1 Enantioselective Enzymatic Reduction of 5-Oxohexanoate and 5-Oxohexanenitrile ............................................................... 235
16.13.2 Enantioselective Microbial Reduction of Substituted Acetophenone ............................................................................... 236
16.14 Anti-Infective Drugs ................................................................................... 237 16.14.1 Microbial Hydroxylation of Pleuromutilin or Mutilin ................. 237 16.14.2 Enzymatic Synthesis of l-β-Hydroxyvaline ................................ 239
16.15 Melatonin Receptor Agonist .......................................................................240 16.15.1 Enantioselective Enzymatic Hydrolysis of Racemic
1-{2′,3′-Dihydro Benzo[b]furan-4′-yl}-1,2-oxirane ......................240 16.15.2 Biocatalytic Dynamic Kinetic Resolution of (R,S)-1-
{2′,3′-Dihydrobenzo[b]furan-4′-yl}-ethane-1,2-diol .................... 241 16.16 Conclusion ..................................................................................................242 Acknowledgments ..................................................................................................242 References ..............................................................................................................242
some examples of the use of enzymes for the synthesis of single enantiomers of key intermediates used in pharmaceutical synthesis.
