137767-91-0Relevant academic research and scientific papers
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.
General Method for the Synthesis of Enantiomerically Pure β-Hydroxy-α-amino Acids, containing Fluorine Atoms in the Side Chains. Case of Stereochemical Distinction between Methyl and Trifluoromethyl Groups. X-Ray Crystal and Molecular Structure of the Nickel(II) Complex of ...
Soloshonok, Vadim A.,Kukhar, Valeri P.,Galushko, Sergei V.,Svistunova, Nataly Yu.,Avilov, Dimitri V.,et al.
, p. 3143 - 3156 (2007/10/02)
The chiral NiII complex 1 of a Schiff's base derived from (S)-o-benzophenone (BPB) and glycine was treated with fluoro-substituted aldehydes (aliphatic and aromatic) in MeOH or CHCl3.The addition proceeds with high diastereoselectivity to give, if catalysed by MeONa in MeOH, the corresponding complexes of syn-(2R)-3-fluorophenylserines (84-100percent) d.e.) and syn-(2S)-fluoroalkylserines (90percent d.e.), and, if catalysed by NEt3 or DABCO (MeOH or CHCl3), the corresponding complexes of syn-(2S)-, and anti-(2S)-3-fluorophenylserines and fluoroalkylserines.The second-order asymmetric transformation may be successfully employed to obtain diastereoisomerically pure complexes of anti-(2R)-3-fluorophenylserines.Condensation of trifluoroacetone with complex 1, catalysed by MeONa, gave predominantly (at least >95percent d.e.) the diastereoisomeric complex, containing (2S,3S)-β-(trifluoromethyl)threonine, as shown by an X-ray diffraction structural study.Diastereoisomerically and enantiomerically pure fluorine-containing 3-phenyl- and 3-alkyl-serines were obtained from the corresponding diastereomerically pure complexes, separated by chromatography or crystallization.The initial chiral auxiliary BPB was recovered (80-98percent).The influence of the reaction's conditions and the nature of the corresponding fluoro-substituted aldehydes on the diastereoselectivity of the reactions is discussed.
