Asymmetric Synthesis of Optically Pure Pharmacologically Relevant Amines Employing ω-Transaminases

✍ Scribed by Dominik Koszelewski; Iván Lavandera; Dorina Clay; David Rozzell; Wolfgang Kroutil

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 247 KB
• Volume: 350
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.200800496

✦ Synopsis

Abstract

Various ω‐transaminases were tested for the synthesis of enantiomerically pure amines from the corresponding ketones employing D‐ or L‐alanine as amino donor and lactate dehydrogenase to remove the side‐product pyruvate to shift the unfavourable reaction equilibrium to the product side. Both enantiomers, (R)‐ and (S)‐amines, could be prepared with up to 99% ee and >99% conversions within 24 h at 50 mM substrate concentration. The activity and stereoselectivity of the amination reaction depended on the ω‐transaminase and substrate employed; furthermore the co‐solvent significantly influenced both the stereoselectivity and activity of the transaminases. Best results were obtained by employing ATA‐117 to obtain the (R)‐enantiomer and ATA‐113 or ATA‐103 to access the (S)‐enantiomer with 15% v v^−1^ DMSO.