Stereoselectivity and regioselectivity of uridine 5'-diphosphoglucuronosyltransferase toward vicinal dihydrodiols of polycyclic aromatic hydrocarbons

Abstract

The ability of a purified rat liver microsomal uridine-5'-diphosphoglucuronosyltransferase to catalyze the glucuronidation of stereoisomeric trans- and cis-9, 10-dihydroxy-9, 10-dihydrophenanthrenes and 4, 5-dihydroxy-4,5-dihydrobenzo[alpha]pyrenes is examined. The enzyme shows the ability to discriminate kinetically between the antipodes of trans-9, 10-dihydroxy-9, 10-dihydrophenanthrene with turnover numbers of 0.070 and 1.4 s-1 and kc/Kmapp values of 4.4 X 10(3) and 1.1 X 10(3) M-1 s-1 for the 9R, 10R and 9S, 10S stereoisomers. Glucuronidation of the nondissymmetric cis-9, 10-dihydroxy-9, 10-dihydrophenanthrene proceeds with a turnover number of 0.037 s-1 and kc/Kmapp of 18 X 10(3) M-1 s-1 to give a 60/40 mixture of the two possible diastereomeric products. Three of the four stereoisomers of 4,5-dihydroxy-4,5-dihydrobenzo[alpha] pyrene are regioselectively glucuronidated by the enzyme with a high degree of kinetic discrimination. Turnover numbers for the 4S,5S, 4R,5R, and 4S,5R stereoisomers are 4.1, 0.37, and 0.23 s-1 with kc/Kmapp values of 23.8 X 10(3), 0.23 X 10(3), and 3.15 X 10(3) M-1 s-1, respectively. The 4R,5S cis isomer is not a substrate. Enzyme-catalyzed reactions of the 4S,5S and 4S,5R isomers give exclusively (greater than or equal to 95%) the 4-glucuronide with the 4R,5R isomer giving the 5-glucuronide. The kinetic and regiochemical results indicate that the enzyme recognizes hydroxyl groups on the beta-face or bottom face of the 4,5-dihydroxy-4,5-dihydrobenzo[alpha]pyrenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Diastereoselective Inter- and Intramolecular Pinacol Coupling of Aldehydes Promoted by Monomeric Titanocene(III) Complex Cp2TiPh

“…Such an intramolecular coupling of an aromatic dial was successfully realized by the catalytic reduction of a biphenylic dial 9d. As expected, a tricyclic diol 10d was obtained in higher yield (70%) with the high trans -selectivity of trans / cis = 91:9 (Table ). In contrast to aliphatic dials, biphenylic dials selectively give trans -diol products in stoichiometric reduction using various low-valent transition metals as shown by Suzuki and co-workers 26a.…”

Highly trans-selective intramolecular pinacol coupling of dials catalyzed by bulky Cp2TiPh

“…1. In addition, the 13 C NMR spectrum of 4c and its melting point are in good agreement with reported data. 12 These results clearly indicate that the bulky Ti IV fragment surrounded by two cyclopentadienyl and one phenyl ligands cannot coordinate to the other carbonyl terminus, and cyclization must proceed via diradical intermediates such as 5, in which two bulky Cp 2 (Ph)TiO moieties occupy axial positions in order to reduce steric repulsion (Fig.…”

“…This is in contrast to the intramolecular coupling of 3b promoted by SmI 2 affording cisproducts via chelated intermediates such as 6. 11 In addition to the aliphatic dials, a biphenylic dial 3d was converted into a tricyclic diol 4d 13 in good yield (70%) with high trans-selectivity (trans : cis = 91 : 9).…”