H-p-Phenyl-D-Phenylalanine

Acrylamide has been reported as an important dietary risk factor from carbohydrate-rich processing food. However, systemic biological effects on the serum metabolomics induced by acrylamide have poorly been understood. In the present study, we evaluated the metabolic profiles in a rat serum after exposure to acrylamide using ultrahigh-performance liquid chromatography combined with quadrupole-orbitrap high-resolution mass spectrometry. The serum biochemical parameters of the treated and control groups were also determined using an automatic biochemical analyzer. Compared with the control group, 10 metabolites were significantly upregulated, including citric acid, d-(-)-fructose, gluconic acid, l-ascorbic acid 2-sulfate, 2-hydroxycinnamic acid, valine, l-phenylalanine, prolylleucine, succinic acid, and cholic acid, while 5 metabolites were significantly downregulated, including 3-hydroxybutyric acid, 4-oxoproline, 2,6-xylidine, 4-phenyl-3-buten-2-one, and N-ethyl-N-methylcathinone in the serum of 4-week-old rats exposed to acrylamide in the high-dose group (all P < 0.05). Importantly, acrylamide exposure affected metabolites mainly involved in the citrate cycle, valine, leucine, and isoleucine biosyntheses, phenylalanine, tyrosine and tryptophan biosyntheses, and pyruvate metabolism. These results suggested that exposure to acrylamide in rats exhibited marked systemic metabolic changes and affected the cardiovascular system. This study will provide a theoretical basis for exploring the toxic mechanism and will contribute to the diagnosis and prevention of acrylamide-induced cardiovascular toxicity.

Enantiomers of a series of hydantoin derivatives were prepared from d- and l-amino acids with p-tolyl isocyanate and 3,5-bis(trifluoromethyl)phenyl isocyanate as guests for chiral recognition by 1H NMR spectroscopy. Meanwhile, several tetraaza macrocyclic compounds were synthesized as chiral solvating agents from d-phenylalanine and (1S,2S)-(+)-1,2-diaminocyclohexane. An uncommon enantiomeric discrimination has been successfully established for hydantoin derivatives, representatives of five-membered N,N-heterocycles, in the presence of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1c by means of 1H NMR spectroscopy. Several unprecedented nonequivalent chemical shifts (up to 1.309 ppm) were observed in the split 1H NMR spectra. To evaluate practical applications in the determination of enantiomeric excess (ee), the ee values of samples with different optical purities (up to 95% ee) were accurately calculated by the integration of relevant proton peaks. To better understand the chiral discriminating behavior, Job plots of (±)-G1 with TAMCSA 1a were investigated. Furthermore, in order to further explore any underlying intermolecular hydrogen bonding interactions, theoretical calculations of the enantiomers of (S)-G1 and (R)-G1 with TAMCSA 1a were performed by means of the hybrid density functional theory (B3LYP/6-31G*) of the Gaussian 16 program.

Biocatalytic processes were used to prepare chiral intermediates required for the synthesis of Omapatrilat 1 by three different routes. The synthesis and enzymatic conversion of 2-keto-6-hydroxyhexanoic acid 3 to L-6-hydroxynorleucine 2 was demonstrated by reductive amination using beef liver glutamate dehydrogenase. To avoid the lengthy chemical synthesis of the ketoacid 3, a second route was developed to prepare the ketoacid by treatment of racemic 6-hydroxy norleucine [readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin 4] with D-amino acid oxidase from porcine kidney or Trigonopsis variabilis followed by reductive amination to convert the mixture completely to L-6-hydroxynorleucine in 98% yield and 99% enantiomeric excess (e.e.). The enzymatic synthesis of (S)-2-amino-5-(1,3-dioxolan-2-yl)-pentanoic acid (allysine ethylene acetal, 5) was demonstrated using phenylalanine dehydrogenase (PDH) from T. intermedius. Phenylalanine dehydrogenase was cloned and overexpressed in Escherichia coli and Pichia pastoris. Using PDH from E. coli or P. pastoris, the enzymatic process was scale-up to prepare kg quantity of allysine ethylene acetal 5. The reaction yields of >94% and e.e. of >98% were obtained for allysine ethylene acetal 5. An enzymatic process was developed for the synthesis of [4S-(4a,7a,10ab)]1-octahydro-5-oxo-4 [[(phenylmethoxy)carbonyl]amino]-7H-pyrido-[2,1-b] [1,3]thiazepine-7-carboxylic acid [BMS-199541-01]. The enzymatic oxidation of the epsilon-amino group of lysine in the dipeptide dimer N(2)-[N[[(phenyl-methoxy)carbonyl] L-homocysteinyl] L-lysine)-1,1-disulphide [BMS-201391-01] to produce BMS-199541-01 using a novel L-lysine epsilon-aminotransferase (LAT) from Sphingomonas paucimobilis SC 16113 was demonstrated. This enzyme was overexpressed in E. coli and a process was developed using the recombinant enzyme.