263396-44-7Relevant articles and documents
The bacterial ammonia lyase EncP: A tunable biocatalyst for the synthesis of unnatural amino acids
Weise, Nicholas J.,Parmeggiani, Fabio,Ahmed, Syed T.,Turner, Nicholas J.
supporting information, p. 12977 - 12983 (2015/10/28)
Enzymes of the class I lyase-like family catalyze the asymmetric addition of ammonia to arylacrylates, yielding high value amino acids as products. Recent examples include the use of phenylalanine ammonia lyases (PALs), either alone or as a gateway to deracemization cascades (giving (S)- or (R)-α-phenylalanine derivatives, respectively), and also eukaryotic phenylalanine aminomutases (PAMs) for the synthesis of the (R)-β-products. Herein, we present the investigation of another family member, EncP from Streptomyces maritimus, thereby expanding the biocatalytic toolbox and enabling the production of the missing (S)-β-isomer. EncP was found to convert a range of arylacrylates to a mixture of (S)-α- and (S)-β-arylalanines, with regioselectivity correlating to the strength of electron-withdrawing/-donating groups on the ring of each substrate. The low regioselectivity of the wild-type enzyme was addressed via structure-based rational design to generate three variants with altered preference for either α- or β-products. By examining various biocatalyst/substrate combinations, it was demonstrated that the amination pattern of the reaction could be tuned to achieve selectivities between 99:1 and 1:99 for β:α-product ratios as desired.
Efficient Kg-Scale Synthesis of Thrombin Inhibitor CRC 220
Jendralla, Heiner,Seuring, Bernhard,Herchen, Joerg,Kulitzscher, Bernd,Wunner, Joachim,et al.
, p. 12047 - 12068 (2007/10/02)
Potent thrombin inhibitor 2 is prepared in 10 steps with 20percent overall yield from commercial 4 on a kg-scale by the convergent approach depicted in Schemes 1 and 2.The (R)-configuration of the 4-amidinophenylalanine piperidide moiety is controlled by asymmetric hydrogenation.A novel method, the hydrogenolysis of amidoximes 11 and 21, is employed to attain a particularly clean transformation of the cyano into the amidinium functionality.Despite of the amorphous nature of target compound 2, the approach is devoid of any chromatographic purification.
