Studies on the synthesis of trans-dihydrodiols of polycyclic aromatic thiaarenes as potential proximate carcinogenic metabolites: First synthesis of trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene and 6,7-dihydroxy-6,7-dihydronaphtho[1,2-b]thiophene

J. K. Ray, S. Gupta, G. K. Kar, B. C. Roy, Jyh ming Lin, Shantu Amin

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Abstract

Polyaromatic thiophene compounds are found to occur concomitantly with numerous coal-derived products and shale oils and are suspected mutagens and/or carcinogens. The first synthesis of the two title compounds 9 and 16 has been achieved in five or four steps starting from 8,9-dihydroacenaphtho[1,2-b]benzo[d]thiophene (1) and 7-methoxynaphtho[1,2-b]thiophene (12), respectively. Compound 1 was converted to the cis-diol (11) (via treatment with OsO4/pyridine) or to trans-diol (3) [via Prevost reaction (PhCOOAg/I2) followed by hydrolysis] in 95-98% yield, respectively. Subsequent dehydration (PTS/benzene) of the diol followed by aromatization of the resulting ketone (5) produced the phenolic compound 6 in 97% yield. Oxidation of the phenol with phenyl iododiacetate followed by hydrolysis of the o-quinone monoketal 7 gave the o-quinone (8) in 86% yield. Stereoselective reduction of 8 with NaBH4/EtOH under oxygen afforded trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene(9) (orange yellow solid) in 55% yield. Compound 16 was obtained as a colorless solid, through the stereoselective reduction of the o-quinone 15 (with NaBH4), which in turn was prepared from 12 following the protocol of functional group transformation of methoxy → phenol → o-quinone monoketal → o-quinone, as used in the previous case. The yields for all the steps are very good. The mutagenicity assay of compound 9 and 16 as well as their parent thiaarenes have been performed. The results showed that 9 may not be the proximate carcinogen of acenaphtho[1,2-b]benzo[d]thiophene, while it is likely that compound 16 is one of the possible proximate carcinogens for naphtho[1,2-b]thiophene.

Original languageEnglish (US)
Pages (from-to)8134-8138
Number of pages5
JournalJournal of Organic Chemistry
Volume65
Issue number24
DOIs
StatePublished - Dec 1 2000

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Metabolites
Thiophenes
Carcinogens
Phenol
Hydrolysis
Shale oil
Aromatization
Coal
Mutagens
Benzene
Ketones
Dehydration
Functional groups
Assays
trans-1,2-dihydro-1,2-naphthalenediol
10,11-dihydroxy-10,11-dihydroacenaphtho(1,2-b)benzo(d)thiophene
6,7-dihydroxy-6,7-dihydronaphtho(1,2-b)thiophene
benzoquinone
Oxygen
Oxidation

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

@article{8f08469eba2c4691958601055773e0d0,
title = "Studies on the synthesis of trans-dihydrodiols of polycyclic aromatic thiaarenes as potential proximate carcinogenic metabolites: First synthesis of trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene and 6,7-dihydroxy-6,7-dihydronaphtho[1,2-b]thiophene",
abstract = "Polyaromatic thiophene compounds are found to occur concomitantly with numerous coal-derived products and shale oils and are suspected mutagens and/or carcinogens. The first synthesis of the two title compounds 9 and 16 has been achieved in five or four steps starting from 8,9-dihydroacenaphtho[1,2-b]benzo[d]thiophene (1) and 7-methoxynaphtho[1,2-b]thiophene (12), respectively. Compound 1 was converted to the cis-diol (11) (via treatment with OsO4/pyridine) or to trans-diol (3) [via Prevost reaction (PhCOOAg/I2) followed by hydrolysis] in 95-98{\%} yield, respectively. Subsequent dehydration (PTS/benzene) of the diol followed by aromatization of the resulting ketone (5) produced the phenolic compound 6 in 97{\%} yield. Oxidation of the phenol with phenyl iododiacetate followed by hydrolysis of the o-quinone monoketal 7 gave the o-quinone (8) in 86{\%} yield. Stereoselective reduction of 8 with NaBH4/EtOH under oxygen afforded trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene(9) (orange yellow solid) in 55{\%} yield. Compound 16 was obtained as a colorless solid, through the stereoselective reduction of the o-quinone 15 (with NaBH4), which in turn was prepared from 12 following the protocol of functional group transformation of methoxy → phenol → o-quinone monoketal → o-quinone, as used in the previous case. The yields for all the steps are very good. The mutagenicity assay of compound 9 and 16 as well as their parent thiaarenes have been performed. The results showed that 9 may not be the proximate carcinogen of acenaphtho[1,2-b]benzo[d]thiophene, while it is likely that compound 16 is one of the possible proximate carcinogens for naphtho[1,2-b]thiophene.",
author = "Ray, {J. K.} and S. Gupta and Kar, {G. K.} and Roy, {B. C.} and Lin, {Jyh ming} and Shantu Amin",
year = "2000",
month = "12",
day = "1",
doi = "10.1021/jo005502+",
language = "English (US)",
volume = "65",
pages = "8134--8138",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "24",

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TY - JOUR

T1 - Studies on the synthesis of trans-dihydrodiols of polycyclic aromatic thiaarenes as potential proximate carcinogenic metabolites

T2 - First synthesis of trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene and 6,7-dihydroxy-6,7-dihydronaphtho[1,2-b]thiophene

AU - Ray, J. K.

AU - Gupta, S.

AU - Kar, G. K.

AU - Roy, B. C.

AU - Lin, Jyh ming

AU - Amin, Shantu

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Polyaromatic thiophene compounds are found to occur concomitantly with numerous coal-derived products and shale oils and are suspected mutagens and/or carcinogens. The first synthesis of the two title compounds 9 and 16 has been achieved in five or four steps starting from 8,9-dihydroacenaphtho[1,2-b]benzo[d]thiophene (1) and 7-methoxynaphtho[1,2-b]thiophene (12), respectively. Compound 1 was converted to the cis-diol (11) (via treatment with OsO4/pyridine) or to trans-diol (3) [via Prevost reaction (PhCOOAg/I2) followed by hydrolysis] in 95-98% yield, respectively. Subsequent dehydration (PTS/benzene) of the diol followed by aromatization of the resulting ketone (5) produced the phenolic compound 6 in 97% yield. Oxidation of the phenol with phenyl iododiacetate followed by hydrolysis of the o-quinone monoketal 7 gave the o-quinone (8) in 86% yield. Stereoselective reduction of 8 with NaBH4/EtOH under oxygen afforded trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene(9) (orange yellow solid) in 55% yield. Compound 16 was obtained as a colorless solid, through the stereoselective reduction of the o-quinone 15 (with NaBH4), which in turn was prepared from 12 following the protocol of functional group transformation of methoxy → phenol → o-quinone monoketal → o-quinone, as used in the previous case. The yields for all the steps are very good. The mutagenicity assay of compound 9 and 16 as well as their parent thiaarenes have been performed. The results showed that 9 may not be the proximate carcinogen of acenaphtho[1,2-b]benzo[d]thiophene, while it is likely that compound 16 is one of the possible proximate carcinogens for naphtho[1,2-b]thiophene.

AB - Polyaromatic thiophene compounds are found to occur concomitantly with numerous coal-derived products and shale oils and are suspected mutagens and/or carcinogens. The first synthesis of the two title compounds 9 and 16 has been achieved in five or four steps starting from 8,9-dihydroacenaphtho[1,2-b]benzo[d]thiophene (1) and 7-methoxynaphtho[1,2-b]thiophene (12), respectively. Compound 1 was converted to the cis-diol (11) (via treatment with OsO4/pyridine) or to trans-diol (3) [via Prevost reaction (PhCOOAg/I2) followed by hydrolysis] in 95-98% yield, respectively. Subsequent dehydration (PTS/benzene) of the diol followed by aromatization of the resulting ketone (5) produced the phenolic compound 6 in 97% yield. Oxidation of the phenol with phenyl iododiacetate followed by hydrolysis of the o-quinone monoketal 7 gave the o-quinone (8) in 86% yield. Stereoselective reduction of 8 with NaBH4/EtOH under oxygen afforded trans-10,11-dihydroxy-10,11-dihydroacenaphtho[1,2-b]benzo[d]thiophene(9) (orange yellow solid) in 55% yield. Compound 16 was obtained as a colorless solid, through the stereoselective reduction of the o-quinone 15 (with NaBH4), which in turn was prepared from 12 following the protocol of functional group transformation of methoxy → phenol → o-quinone monoketal → o-quinone, as used in the previous case. The yields for all the steps are very good. The mutagenicity assay of compound 9 and 16 as well as their parent thiaarenes have been performed. The results showed that 9 may not be the proximate carcinogen of acenaphtho[1,2-b]benzo[d]thiophene, while it is likely that compound 16 is one of the possible proximate carcinogens for naphtho[1,2-b]thiophene.

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U2 - 10.1021/jo005502+

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IS - 24

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