The chiral switch

For small-scale chemistry, the practical value of the specificity and selectivity inherent in enzymatic catalysis is increasingly recognized. The topic is the subject of a number of recent books (see the Bibliography at the end of each chapter), and the current literature is full of examples. There may be some resistance to the large-scale use of enzymes, but there are now enough manufacturing processes in operation to demonstrate the effectiveness of the technology. 

The authorities who licence pharmaceuticals have begun to argue that where the products are chiral, then the isomers should be separated and 

The lactate dehydrogenases which are responsible in whole organisms for the synthesis of one or other enantiomer of lactic add will also synthesize a range of substituted -hydroxy adds from -keto adds. The purified enzymes are used, and the reactions are more complex than those which the lyases catalyse, in that they require NADH as a reducing agent. This must 

D-glycerol-3-phosphate (s -glycerol-3-phosphate) (47X which is used in phospholipid manufacture, is another synthon whose production requires the recycling of a co-factor. It is synthesized from glycerol and ATP, with 

The suppliers of fine chemicals initially produce many new chiral compounds in kilogram amounts on the assumption that scale-up to an annual production of about 1 tonne is practical. The pharmaceutical industry almost certainly produces other synthons on this scale from its own resources. The outcome is likely to be an increasing use of enzymes in 

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The enantioselective hydrogenation of C=N bonds is the least-developed hydrogenation reaction, even though many active ingredients contain chiral amine moieties. The main reason for this situation is that effective catalysts - mainly Ir-diphosphine complexes - have been developed only during the past 10 years [124]. A major incentive for the development of more active catalysts was the chiral switch of metolachlor made in 1997 by Ciba-Geigy [125, 126]. 

Blaser, H.-U. The Chiral Switch of (S)-Metolachlor A Personal Account of an Industrial Odyssey in Asymmetric Catalysis. Adv. Synth. Catal. 2002, 344, 17-31. 

The chiral switch of the metolachlor was achieved in 1997. It was put on the market with a content of approximately 90% of the Sc active diastereomers. The key step of the large-scale enantioselective synthesis is the catalytic hydrogenation of the MEA imine shown in Figure 17. A mixture of [IrCl(l,5-cyclooctadiene)]2, the chiral diphosphine (i ,5)-xylyphos, iodide (as tetrabutylammonium or sodium salts) and acetic (30%) or sulfuric (at low... 

The chiral switch of Metola-clilor the development of a large-scale enantioselective catalytic process Enantioselective hydrogenation towards a large-scale total synthesis of (R,R,R)-a-tocopher-ol... 

The Chiral Switch of Metolachlor The Development of a Large-Scale Enantioselective Catalytic Process1... 

The chiral switch from the racemate to an enriched form is attractive not only for pharmaceuticals but also for agrochemicals, and enantioselective hydrogenation is a particularly suitable and commercially feasible technology to allow this. 

Hutt, A, and Valentova, J. (2003). The chiral switch The development of single enantiomers drugs from racemates, Acta Facult. Pharm. Univ. Comenianae., 50, 7-23. 

Table 13.1 illustrates some examples of the chiral switch among APIs. ... 

Blaser H-U (2002) The chiral switch of (S)-metolachlor a personal account of an industrial odyssey in asymmetric catalysis. Adv Synth Catal 344 17-31... 

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