A Chirality Chain in Phenylglycine, Phenylpropionic Acid, and Ibuprofen

Our strategy to analyze the structures of natural amino acids with respect to the interaction of three different elements of chirality within the molecules was applied to the non-natural amino acid (S)-α-phenylglycine, its analogue (S)-α-phenylpropionic acid, and the drug (S)-ibuprofen. The three chirality elements are the configuration at Cα, the conformation at the Cα-C’ bond, and the distortion of the planar carboxylic group to a flat asymmetric tetrahedron. In all three compounds, a given (S) configuration at Cα predominantly induces (M) conformation at the Cα-C’ bond, which in turn preferentially distorts the carboxylic group to a tetrahedron with (R) configuration. Both steps of this chirality chain display high selectivities. Due to varying co-crystallization partners, in all the structures the molecules are in different environments with respect to packing and hydrogen bonding. Nevertheless, the structural pattern and the diaselectivities of the chirality chain persist. For phenylglycine, DFT (Density Functional Theory) calculations confirm the structural results.

Bornyl Derivatives of p-(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity

A series of bornyl derivatives of p-(benzyloxy)phenylpropionic acid were prepared, and their hypoglycemic activities were examined by an oral glucose tolerance test in mice. The results of this test revealed two compounds, 1 and 3, that can reduce the blood level of glucose similarly to reference compound vildagliptin. Both compounds were tested in an experiment on mice with metabolic disorders: the C57BL/6Ay strain. Along with hypoglycemic properties, the two compounds showed different abilities to correct lipid metabolism disorders. In silico prediction revealed that the studied substances are most likely bifunctional multitarget hypoglycemic compounds whose mechanism of action is based on a pronounced reduction in insulin resistance and a strong incretin-mimetic effect. The difference in the size of effects of these compounds on biochemical parameters of blood in the experiment on C57BL/6Ay mice was in good agreement with the computational prediction of the priority ranking of biological targets for these compounds. These results indicate that bornyl derivatives of p-(benzyloxy)phenylpropionic acid have a good potential as new agents for diabetes mellitus treatment due to their hypoglycemic and lipid-normalizing properties.

Preparation of (S)-2-Phenylpropionic Acid by CaCl2/CMC Nanoparticles Immobilized Candida rugosa Lipase-Catalyzed Hydrolysis in Micro Aqueous Mixed Organic Solvent Systems

Candida rugosa lipase was immobilized in this study using CaCl2/CMC nanoparticles that yielded a lipase loading capacity of 127 mg/g, with better thermal stability and activity of 91.8%. The hydrolysis of racemic 2-phenylpropionic acid isopropyl ester by free and immobilized Candida rugosa lipase was investigated in the mixed organic-solvent composed of isooctane and methyl tert-butyl ether (9.5:0.5, V/V). The optimal conditions were 35 °C and pH 7.5 for free Candida rugosa lipase hydrolysis. We obtained (S)-2-phenylpropionic acid with 44.85% conversion, 95.75% enantiomeric excess and enantiomeric ratio of 112. The CaCl2/CMC nanoparticles immobilized Candida rugosa lipase possesses high enantioselectivity, with E = 237 at 40 °C and pH 7.5. It was efficiently reusable in four cycles and appropriately enhanced enantioselectivity within 120–240.

Preparation of Palladium(II) Complexes of 1-substituted-3-phospholene Ligands and their Evaluation as Catalysts in Hydroalkoxycarbonylation

: A series of palladium(II) complexes incorporating 1-substituted-3-methyl-3- phospholenes as the P-ligands were prepared from phospholene oxides by deoxygenation followed by complexation with PdCl2(PhCN)2. The two 1-substituted-3-methyl-3- phospholene ligands were trans position to each other in the Pd(II)-complexes. As the ligands contain a P-stereogenic center, the Pd-complexes were obtained as a 1:1 mixture of two stereoisomers, the homochiral (R,R and S,S) and the meso (R,S) forms, when racemic starting materials were used. An optically active Pd-complex containing (R)-1-propyl- 3-phospholene ligand was also prepared. Catalytic activity of an aryl- and an alkyl-3- phospholene-palladium(II)-complex was evaluated in hydroalkoxycarbonylation of styrene. The alkyl-derivative showed higher activity and selectivity towards the formation of the esters of 3-phenylpropionic acid. However, the overall activity of these PdCl2(phospholene)2-type complexes was low.