Biocatalysis dynamic kinetic resolution

Dynamic Kinetic Resolution of Amines Involving Biocatalysis and In Situ Free-radical-mediated Racemization... 

Gastaldi, S., Escoubet, S., Vanthuyne, N., Gil, G. and Bertrand, M.P., Dynamic kinetic resolution of amines involving biocatalysis and in situ free radical mediated racemization. Org. Lett., 2007, 9, 837-839. 

As well as biocatalysis in neat organic solvents and biphasic systems (fundamentals and synthetic applications), the present volume covers new and promising aspects of non-aqueous enzymology that have emerged in recent years, including biocatalysis with undissolved solid substrates or vaporized compounds, the use of ionic liquids as solvents, and the preparative-scale exploitation of oxynitrilases and dynamic kinetic resolutions . For the sake of completeness and comparison,... 

An excellent example of the successful combination of chemo- and biocatalysis in a two-step cascade process is provided by the dynamic kinetic resolutions (DKR) of chiral alcohols and amines. We first suggested [6], in 1993, that (de)-hydrogenation catalysts should be capable of catalyzing the racemization of chiral alcohols and amines via a dehydrogenation/hydrogenation mechanism as shown in Fig. 9.1. 

Kim, M.-J., Ahn, Y., Park, J. Dynamic kinetic resolution and asymmetric transformations by enzyme-metal combination. In Biocatalysis in the Pharmaceutical and Biotechnology Industries (ed. Patel, R.N.), 2007, CRC Press, Boca Raton, FL, 249-272. 

Another example, from the Pfizer portfolio, of successful incorporation of biocatalysis to make functional group interconversions (FGIs) more efficient in API synthesis is in a program for a smoothened (SMO) receptor inhibitor [17], Introduction of a transaminase-catalyzed stereoselective reductive amination of a 4-piperidone 4 with concurrent dynamic kinetic resolution (DKR) gave amine 5 (Scheme 7.2), resulting in the highly efficient incorporation of two chiral centers in a single step. 

Hetero Diels-Alder-Biocatalysis approach for the synthesis of (S)-3- 2-[(methyl-sulfonyl) oxy]ethoxy -4-(triphenylmeth-oxy)-l-butanol methanesulfo-nate successful application of an enzyme resolution process Multi-kilo resolution of XU305, a key intermediate to the platelet glycoprotein Ilb/IIIa receptor antagonist roxifiban via kinetic and dynamic enzymatic resolution... 

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