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2.4.3.4.2 Deracemization via Deamination/Transamination

DOI: 10.1055/sos-SD-215-00213

Simon, R. C.; Busto, E.; Fischereder, E.-M.; Fuchs, C. S.; Pressnitz, D.; Richter, N.; Kroutil, W.Science of Synthesis: Biocatalysis in Organic Synthesis, (20152414.

Enzymatic deracemization represents an interesting method for the synthesis of enantiopure compounds from racemic amines, theoretically providing the optically pure amine in 100% yield. For example, a process for the deracemization of mexiletine (30) by ω-transaminases in a one-pot two-step procedure leading to either enantiomer in up to >99% conversion and >99% enantiomeric excess has been described.[‌20‌,‌21‌] In the first step, kinetic resolution of the amine 30 is performed (Scheme 20), followed by a stereoselective transamination of the formed intermediate ketone 31 in the second step. The pyruvate consumed in the first step is recycled in situ by an amino acid oxidase (DAAO). To improve the deracemization approach of mexiletine described above, immobilized ω-transaminase has been employed, with the enzyme immobilized in a sol-gel/Celite matrix. In contrast to free enzymes, the sol-gel immobilized ω-transaminases are easily removable by centrifugation or filtration after the first step.[‌86‌] The sol-gel entrapment represents an easy and effective way to prepare high-performance amines. Using this approach (S)-mexiletine [(S)-30] is obtained in enantiomerically pure form and up to 95% isolated yield.[‌20‌]

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References