Synthesis and antiinflammatory activity of 4-(p-biphenylyl)-3-hydroxybutyric acid and related compounds

Synthesis of optically active methyl 4-(4-biphenylyl)-3-hydroxybutanoate via enantioselective hydrogenation using a tartaric acid-modified nickel catalyst and recrystallization

“…This is a very fortunate result because many c-aromatic-b-hydroxybutanoate esters are not crystalline at least in their racemic forms. 1 We also prepared methyl 4-(1-naphthyl)-3-hydroxybutanoate and methyl 4-(3,4-dimethoxyphenyl)-3-hydroxybutanoate in the racemic forms, but they were not obtained as crystals. Recrystallization of the enantiomerically impure 2 was performed with toluene, diisopropyl ether, cyclopropyl methyl ether, and ethyl acetate as solvents.…”

“…Substrate 1 was prepared from 4-biphenylylacetic acid and Meldrum's acid (76% for two steps). 11 Mp 82.9-83.4°C; 1 …”

“…The initial hydrogen pressure was 9 MPa and the hydrogenation temperature was 333 K (or 373 K). The reaction mixture was filtrated after cooling, and analyzed by 1 Racemic 2 was also prepared by the sodium borohydride reduction of 1. The spectral data were identical with optically active ones including IR spectrum (KBr), except for a broader melting point (92.0-94.2°C).…”

“…Of the compounds tested, 4-(4-biphenylyl)-3-hydroxybutanoic acid and its esters have the highest activity, and show 2.5-5.6 times higher pharmacological activities than phenylbutazone, a common non-steroidal anti-inflammatory drug. 1 In addition, optically active 4-aryl-3-hydroxybutanoate esters can be precursors for 3-alkoxyglutaric acid half esters, key synthetic units for various natural and unnatural bioactive compounds. 2 Such optically active bhydroxyesters are obtained by the enantioselective hydrogenation of the corresponding b-ketoesters using either homogeneous or heterogeneous chiral catalysts.…”

Enantioselective Reduction of β‐Keto Acids with Engineered Streptomyces coelicolor

“…: 126-127 8C (lit. : 126-128 8C [13] ); [a] D + 1.17 (c = 1.03, CHCl 3 ); IR (neat): ñ max = 3406, 2923, 1695 cm À1 ; 1 H NMR (400 MHz, CD 3 OD): d = 2.56 (dd, J = 10.4, 5.3 Hz, 1 H, CHCO 2 H), 2.63 (dd, J = 10.4, 2.3 Hz, 1 H, CHCO 2 H), 2.98 (dd, J = 8.5, 3.9 Hz, 1 H, CHAr), 3.03 (dd, J = 8.5, 4.4 Hz, 1 H, CHAr), 4.33-4.41 (m, 1 H, CHOH), 7.29 (dd, J = 5.3, 0.9 Hz, 1 H, ArH), 7.31-7.36 (m, 2 H, ArH), 7.59 (s, 1 H, ArH), 7.67-7.71 ppm (m, 3 H, ArH); 13…”