Chemoenzymatic processes scale

An Integrated Approach to Developing Chemoenzymatic Processes at the Industrial Scale... 

Attempts to use the secosteroid biosynthetic enzymes in a chemoenzymatic synthesis have recently proved successful. An acetone powder from P. americana transformed gorgosterol to 9(11)-secogorgosterol in a quantitative yield on a 5 mg scale [82]. The transformation was found to require both NAD and NADP. Interestingly, this chemoenzymatic process proved to be applicable to the production of a variety of known and novel 9( 11 )-secosterols indicating the lack of specificity of the enzymes involved and the utility as a synthetic tool [83], The secosteroids 48 - 51 were produced from their corresponding steroid in yields of 30 - 78%. 

Purkarthofer, T., Pabst, T., van den Broek, C. et al. (2006) Large-scale synthesis of (/ )-2-amino-l-(2-furyl) ethanol via a chemoenzymatic approach. Organic Process Research Development, 10, 618-621. 

Finally, natural (i )-(-)-mevalonolactone, a key intermediate from a broad spectrum of cellular biological processes and their regulation, was synthesised via eight steps in 55% overall yield and > 99% ee (Scheme 19). In the key step, the aforementioned enantioconvergent chemoenzymatic deracemization route was applied. Thus, 2-methyl-2-benzyl-oxirane ( )-2 g was deracemized on a large scale (10 g) using lyophilized cells of Nocardia EHl and sulfuric... 

Blayer S, Woodley JM, Dawson MJ, Lilly MD (1995) Process Development for Scale-Up of Biotransformations Chemoenzymatic Synthesis of N-Acetylncuraminic Acid. Biotrans 95, Warwick, UK... 

The asymmetric hydrolysis of (exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol, diacetate ester (37) to the corresponding chiral monoacetate ester (38) (Fig. 12B) has been demonstrated with lipases [61]. Lipase PS-30 from P. cepacia was most effective in asymmetric hydrolysis to obtain the desired enantiomer of monoacetate ester. The reaction yield of 75 M% and e.e. of >99% were obtained when the reaction was conducted in a biphasic system with 10% toluene at 5 g/liter of the substrate. Lipase PS-30 was immobilized on Accurel PP and the immobilized enzyme was reused (5 cycles) without loss of enzyme activity, productivity, or e.e. of product (38). The reaction process was scaled up to 80 liters (400 g of substrate) and monoacetate ester (38) was isolated in 80 M% yield with 99.3% e.e. The product was isolated in 99.5% chemical purity. The chiral monoacetate ester (38) was oxidized to its corresponding aldehyde and subsequently hydrolyzed to give chiral lactol (33) (Fig. 12B). The chiral lactol (33) obtained by this enzymatic process was used in chemoenzymatic synthesis of thromboxane A2 antagonist (35). 

Fig. 10) [165], The Cytel corporation in San Diego has been able to scale-up this process for the routine production of kilogram quantities in each run of reactions [144]. The sialyl Le tetrasaccharide and its analogs are of pharmaceutical interest in the context of new treatments for chronic inflammatory diseases (psoriasis, rheumatoid arthritis), tumors, and tissue injuries following a heart attack, stroke, or organ transplant. Sialyl Lex and its analogs are therefore enthusiastically pursued by several pharmaceutical companies. Strategies for the solid-phase chemoenzymatic synthesis of glycopeptides (and glycolipids) containing sialyl Lex have also been designed and reported [144,156, and references therein].

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