IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Metabolism of the proximate carcinogen trans-3,4-dihydroxy-3,4dihydrodibenz[c,h]acridine has been examined with rat liver enzymes. The dihydrodiol is metabolized at a rate of 2.4 nmol/nmol of cytochrome P450 1A1/min with microsomes from 3-methylcholanthrene-treated rats, a rate more than 10-fold higher than that observed with microsomes from control or phenobarbital-treated rats. Major metabolises consisted of a diastereomeric pair of bis-dihydrodiols (68-83%), where the new dihydrodiol group has been introduced at the 8,9-position, tetraols derived from bay region 3,4-diol-1,2-epoxides (15-23%), and a small amount of a phenolic dihydrodiol(s) where the new hydroxy group is at the 8,9-position of the substrate. A highly purified monooxygenase system reconstituted with cytochrome P450 1A1 and epoxide hydrolase (17 nmol of metabolites/nmol of cytochrome P450 1A1/min) gave a metabolite profile very similar to that observed with liver microsomes from 3-methylcholanthrene-treated rats. Study of the stereoselectivity of these microsomes established that the (+)-(3S,4S)-dihydrodiol gave mainly the diol epoxide-1 diastereomer, in which the benzylic 4-hydroxyl group and epoxide oxygen are cis. The (-)-(3R,4R)-dihydrodiol gave mainly diol epoxide-2 where these same groups are trans. The major enantiomers of the diastereomeric bis-dihydrodiols are shown to have the same absolute configuration at the 8,9-position. Correlations of circular dichroism spectra suggest this configuration to be (8R,9R). The (8R,9S)-oxide may be their common precursor. Copyright (C) 1999 Elsevier Science Ireland Ltd.

World University root node

Department Of Biotechnology

Chemico-Biological Interactions

The proximate carcinogen trans-3,4-dihydroxy-3,4-dihydro-dibenz[c,h]acridine is oxidized stereoselectively and regioselectively by cytochrome 1A1, epoxide hydrolase and hepatic microsomes from 3-methylcholanthrene-treated rats

Lithium perchlorate/diethyl ether (LPDE) mediated rearrangement of α- and β-endo-dicylopentadienyl vinyl ethers 5 and 6 resulted in the formation of the aldehyde 8, indicating that the mechanism is nonconcerted and the recombination of the ion pair occurs at the dissociated stage and not the intimate ion-pair stage. Proof of this came from deuterium-labeling studies and the use of an optically pure starting material. Furthermore, that the ionic intermediate formed must be symmetrical resulting in enantiomeric aldehydes from both normal and allylic attack corresponding to products of formal 1,3 and 3,3 shifts was seen in the chiral analysis of the benzoate derivative of the aldehydes formed from the optically pure vinyl ether.

GENERAL

Journal of Organic Chemistry

Mechanism of lithium perchlorate/diethyl ether-catalyzed rearrangement of α- and β-endo- and -exo-dicyclopentadienyl vinyl ethers: Use of deuterium labeling and a chiral probe

Plant cell cultures of carrot have been used to effect the asymmetric reduction of 2-oxo-4-phenylbutanoic acid ethyl ester to (R)-2-hydroxy-4-phenylbutanoic acid ethyl ester in high enantiomeric excess and yield.

Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry

Biotransformations by plant cell cultures

A novel method to produce (R)-(-)-2-hydroxy-4-phenylbutanoic acid ethyl ester 1b has been developed 2-Oxo-4-phenylbutanoic acid ethyl ester 1a reduced to 1b by the cell cultures of Daucus carets in high enantiomeric excess and yield.

Tetrahedron Asymmetry

Asymmetric reduction of 2-oxo-4-phenylbutanoic acid ethyl ester by Daucus carota cell cultures

Racemic 2-hydroxy-4-phenylbutanoic acid and 2-hydroxy-4-phenyl-butenoic acid have been resolved using a lipase. In each case, the (R)-2-hydroxy and the (S)-2-acetoxy acids were isolated with high enantiomeric excess and yield. © 1995.

Tetrahedron: Asymmetry

Enzymatic resolution of 2-hydroxy-4-phenylbutanoic acid and 2-hydroxy-4-phenylbutenoic acid

Chemical structures of the principal covalent adducts formed from DNA upon reaction in vitro with the four optically active 3,4-diol 1,2-epoxides of benz[a] anthracene have been elucidated at the nucleoside level. In addition to adducts formed by cis and trans addition of the exocyclic amino groups of deoxyadenosine (dA) and deoxyguanosine (dG) and a trans deoxycytidine (dC) adduct, chemical characterization of a deglycosylated N-7 dG adduct formed in DNA by trans opening of the (4S, 3R)-diol (2R, 1S)-epoxide isomer is reported. Relative stereochemistries of the adducts (cis versus trans opening of the epoxides by the exocyclic amino groups) were deduced from the coupling constants of the methine protons of the tetrahydro benzo rings of the acetylated derivatives. Adducts having (S)-configuration at the attachment site on the hydrocarbon moiety have CD spectra that exhibit a positive band at 250–260 nm and a negative band at longer wavelengths, whereas (R)-configuration at this center gives rise to CD spectra with bands of approximately equal intensity and opposite sign. This allowed assignment of cis versus trans addition to the chiral epoxides for adducts that were not generated in sufficient quantity to obtain NMR spectra. Analysis of the patterns of adducts derived from benz[a] anthracene, benzo[c]phenanthrene, and benzo[a]pyrene shows that the comparative tumorigenicities of the diol epoxide isomers of each hydrocarbon do not correlate well with the extent of adduct formation, the ratio of cis versus trans addition to the epoxide, the propensity for forming adducts at dC or the N-7 position of dG, or the ratio of adduct formation at dA versus dG, although tumorigenicity may correlate with the ability to form dG adducts with (S)-configuration at the N-substituted benzylic carbon, especially those arising from trans addition to the epoxide. © 1993, American Chemical Society. All rights reserved.

Structures of Covalent Nucleoside Adducts Formed from Adenine, Guanine, and Cytosine Bases of DNA and the Optically Active Bay-Region 3,4-Diol 1,2-Epoxides of Benz[a]anthracene

(R) and (S)-t-butyloxirane [(R)- and (S)-3] have been prepared in high enantiomeric purity from racemic t-butyloxirane (±)-3 by an enzymatic route. (S)-3 has been used for the preparation of the chiral β-amino alcohols (R)- and (S)-1,2, which are catalysts for the enantioselective addition of dialkylzinc reagents to aldehydes. © 1993.

A facile enzyme assisted route to (R) - and (S)-t-butyloxirane and related β-amino alcohols - catalysts for the enantioselective addition of dialkylzinc reagents to aldehydes

Advances in Experimental Medicine and Biology

Covalent bonding of bay-region diol epoxides to nucleic acids

The diastereomeric 7,8-diol 9,10-epoxides metabolically derived from the carcinogenic hydrocarbon benzo-[α]pyrene react with the purine bases in nucleic acids to alkylate their exocyclic amino groups. The major adducts formed from polyguanylic acid and the enantiomers of diol epoxide-1 (the diastereomer in which the benzylic 7-hydroxyl group and the epoxide oxygen are cis) have been shown to result from cis opening of the epoxide by the N-2 amino group of guanine, rather than trans opening as had been previously reported. Four adducts resulting from alkylation of the exocyclic N-6 amino group of adenosine 5′-monophosphate by racemic diol epoxide-1 have been prepared and characterized. In addition, a major adduct formed from adenosine 5′-monophosphate and (-)-(7R, 8S)-diol (9R, 10S)-epoxide-l, but not from its (+) enantiomer, has been identified as a product of alkylation of the 2′-hydroxyl group of the sugar. We also report a quantitative reevaluation of the extent and distribution of covalent adduct formation from calf thymus DNA and both diastereomeric benzo[α]pyrene diol epoxides, as well as the identification of the principal DNA adducts formed from the enantiomers of diol epoxide-1. Tentative identification of several new minor adducts formed upon reaction of diol epoxide-2 with denatured DNA is described. The present results provide additional support for our previously proposed correlation between the signs of the circular dichroism bands of these adducts and their absolute configurations at the N-substituted benzylic carbon atom. © 1991, American Chemical Society. All rights reserved.

Covalent Nucleoside Adducts of Benzo[a]pyrene 7,8-Diol 9,10-Epoxides: Structural Reinvestigation and Characterization of a Novel Adenosine Adduct on the Ribose Moiety

Bulletin of Environmental Contamination and Toxicology

Metabolism of 1,8-Cineole in Rat: Its effects on liver and lung microsomal cytochrome P-450 systems

1. Metabolites isolated from the urine of rats after oral administration of geraniol (I) were: geranic acid (II), 3-hydroxy-citronellic acid (III), 8-hydroxy-geraniol (IV), 8-carboxy-geraniol (V) and Hildebrandt acid (VI). 2. Metabolites isolated from urine of rats after oral administration of linalool (VII) were 8-hydroxy-linalool (VIII) and 8-carboxy-linalool (IX). 3. After three days of feeding rats with either geraniol or linalool, liver-microsomal cytochrome P-450 was increased. Both NADH- and NADPH-cytochrome c reductase activities were not significantly changed during the six days of treatment. 4. Oral administration of these two terpenoids did not affect any of the lung-microsomal parameters measured. © 1984 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Xenobiotica

Metabolism of geraniol and linalool in the rat and effects on liver and lung microsomal enzymes

Rat lung microsomes were shown to ω-hydroxylate acyclic monoterpene alcohols in the presence of NADPH and O2. NADH could neither support hydroxylation efficiently nor did it show synergistic effect. The hydroxylase activity was greater in microsomes prepared from β-naphthoflavone (BNF)-treated rats than from phenobarbital (PB)-treated or control microsomal preparations. Hydroxylation was specific to the C-8 position in geraniol and has a pH optimum of 7.8. The inhibition of the hydroxylase activity by SKF-525A, CO, N-ethylmaleimide, ellipticine, α-naphthoflavone, cyt. c and p-CMB indicated the involvement of the cyt. P-450 system. However, NaN3 stimulated the hydroxylase activity to a significant level. Rat kidney microsomes were also capable of ω-hydroxylating geraniol although the activity was lower than that observed with lungs. © 1982.