Chemoenzymatic Process Development

Tao, J., Zhao, L. and Ran, N. (2007) Recent advances in developing chemoenzymatic processes for active pharmaceutical ingredients. Organic Process Research Development, 11, 259-267. 

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

Chemoenzymatic processes involving oxidizing enzymes have been reported particularly for specific chemical syntheses. For example, industrially important amino acids can be deracemized by exploiting the enantioselectivity of amino acid oxidases a commercial process has recently been developed in which efficient... 

Epoxide hydrolases are less used than lipases however, in recent years the synthesis of chiral diols with these biocatalysts has emerged as an excellent methodology to develop new and interesting chemoenzymatic processes [13],... 

The Development of Short, Efficient, Economic, and Sustainable Chemoenzymatic Processes... 

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... 

A chemoenzymatic process for the preparation of D- and L-t/ireo-phenylisoserine and derivatives thereof has been developed by Celgene. This process integrates an Erlenmeyer condensation as an initial chemical step which produces racemic threo... 

Although initially prepared and evaluated as a racemate, the NMDA antagonist activity was likely to reside primarily in a single enantiomer. The stereoselective nature of the NDMA receptor is well established, albeit not completely understood. Consequently, several attempts have been undertaken to develop synthetic protocols that would allow preparation of optically active compounds. Early reports of preparation of optically active co-amino-o-carboxyalkylphosphonic acids describe the preparation of (.S )-A P-3 from an optically active amino nitrile prepared by reaction of diethyl 1-formylphosphonate with hydrogen cyanide and (5)-(-)-a-methylbenzylamine. Acid hydrolysis, enrichment of the diastereomers by fractional recrystaUization, and debenzylation lead to the isolation of (.S )-A P-3 in 86% enantiomeric excess. " Recently reported procedures, which use chemoenzymatic processes, offer a more convenient and mild approach for the production of optically pure aminophosphonic acids. Enzymatic hydrolysis of amides using penicillinacylase (EC... 

As a part of ongoing efforts to synthesize a potent, orally active anti-platelet agent, xemilofiban 1 [1], development of an efficient chemoenzymatic process for 2, the chiral yS-amino acid ester synthon (Fig. 1) was proposed. The scheme emphasized the creation of the stereogenic center as the key step. In parallel with the enzymatic approach, chemical synthesis of the / -amino acid ester synthon emphasized formation of a chiral imine, nucleophilic addition of the Reformatsky reagent, and oxidative removal of the chiral auxiliary. This chapter describes a selective amida-tion/amide hydrolysis using the enzyme Penicillin G amidohydrolase from E. coli to synthesize (R)- and (S)-enantiomers of ethyl 3-amino-5-(trimethylsilyl)-4-pen-tynoate in an optically pure form. The design of the experimental approach was applied in order to optimize the critical reaction parameters to control the stereoselectivity of the enzyme Penicillin G amidohydrolase. 

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