5872-74-2Relevant articles and documents
Exploring the scope of an α/β-aminomutase for the amination of cinnamate epoxides to arylserines and arylisoserines
Shee, Prakash K.,Ratnayake, Nishanka Dilini,Walter, Tyler,Goethe, Olivia,Onyeozili, Edith Ndubuaku,Walker, Kevin D.
, p. 7418 - 7430 (2019/08/20)
Biocatalytic process-development continues to advance toward discovering alternative transformation reactions to synthesize fine chemicals. Here, a 5-methylidene-3,5-dihydro-4H-imidazol-4-one (MIO)-dependent phenylalanine aminomutase from Taxus canadensis (TcPAM) was repurposed to irreversibly biocatalyze an intermolecular amine transfer reaction that converted ring-substituted trans-cinnamate epoxide racemates to their corresponding arylserines. From among 12 substrates, the aminomutase ring-opened 3′-Cl-cinnamate epoxide to 3′-Cl-phenylserine 140 times faster than it opened the 4′-Cl-isomer, which was turned over slowest among all epoxides tested. GC/MS analysis of chiral auxiliary derivatives of the biocatalyzed phenylserine analogues showed that the TcPAM-transamination reaction opened the epoxides enantio- A nd diastereoselectively. Each product mixture contained (2S)+(2R)-anti (erythro) and (2S)+(2R)-syn (threo) pairs with the anti-isomers predominating (-90:10 dr). Integrating the vicinal proton signals in the 1H NMR spectrum of the enzyme-catalyzed phenylserines and calculating the chemical shift difference (?"?) between the anti and syn proton signals confirmed the diastereomeric ratios and relative stereochemistries. Application of a (2S)-threonine aldolase from E. coli further established the absolute stereochemistry of the chiral derivatives of the diastereomeric enzymatically derived products. The 2R:2S ratio for the biocatalyzed anti-isomers was highest (88:12) for 3′-NO2-phenylserine and lowest (66:34) for 4′-F-phenylserine. This showed that the stereospecificity of TcPAM is in part directed by the substituent-type on the cinnamate epoxide analogue. The catalyst also converted each cinnamate epoxide analogue to its corresponding isoserine, highlighting a biocatalytic route to arylisoserines, which play a key role in building the pharmacophore seen in anticancer and protease inhibitor drugs.
Neighbouring group effects promote substitution reactions over elimination and provide a stereocontrolled route to chloramphenicol
Easton, Christopher J.,Hutton, Craig A.,Merrett, Martin C.,Tiekink, Edward R. T.
, p. 7025 - 7036 (2007/10/03)
In reactions of β-brominated valine and p-nitrophenylalanine derivatives to give β-hydroxy amino acid derivatives the carboxyl group, when protected as an amide, exerts a neighbouring group effect to facilitate the substitution process, and reduce competing elimination reactions. As a consequence of the effect, the (2R,3R)- and (2R,3S)-stereoisomers of 3-bromo-N-tert-butyl-N(α)-phthaloyl-p-nitrophenylalaninamide both react to give (2S,3R)-3-hydroxy-N-tert-butyl-N(α)-phthaloyl-p-nitrophenylalaninamid e, providing a stereoconvergent route to chloramphenicol.
