Revised assignment of absolute configuration of the cis- and trans-N6-deoxyadenosine adducts at C14 of (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene by stereoselective synthesis.

2.50
Hdl Handle:
http://hdl.handle.net/10146/84154
Title:
Revised assignment of absolute configuration of the cis- and trans-N6-deoxyadenosine adducts at C14 of (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene by stereoselective synthesis.
Authors:
Yagi, Haruhiko; Frank, Heinrich; Seidel, Albrecht; Jerina, Donald M.
Abstract:
We have reassigned relative and absolute configurations by unambiguous stereoselective syntheses of the cis- (13s and 13R) and trans-N6-deoxyadenosine (dAdo) adduct diastereomers (14S and 14R) derived from (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]P DE-2), previously reported by Li et al. [(1999) Chem. Res. Toxicol. 12, 758-767]. Two stereoselective methods, asymmetric aminohydroxylation of the (+/-)-trans-11,12-dihydrodiol (3) with 3',5'-di-O-(tert -butyldimethylsilyl)-2'-deoxyadenosine (4) and the highly stereoselective cis addition of 4 to (+/-)-DB[a,l]P DE-2 in hexafluoropropan-2-ol (HFP), were employed. Both afforded a 1:1 mixture of the cis-N6-dAdo adduct diastereomers, which were separated as triacetates (5S and 5R) in comparable yields (approximately 80%). The corresponding trans adduct diastereomers (10S and 10R) were obtained by coupling the aminotriol derived from trans opening of (+/-)-DB[a,l]P DE-2 with 6-fluoro-(2'-deoxy-3,5-di-tert-butyldimethylsilyloxy-beta-D-erythro-pentafuranosyl)purine (9) and subsequent acetylation in approximately 70% yield. The cis-5S and -5R and trans-10S and -10R were separately treated with 7% HF-pyridine followed by ammonolysis in NH3-saturated MeOH to give the dAdo adducts with all hydroxyl groups free (13S, 13R, 14S, and 14R). Comparison of the 1H NMR and CD spectra of these presently synthesized dAdo adducts with spectra of the previously reported compounds revealed that the interpretation of the 1H NMR and CD spectra and assignment of the relative stereochemistry (cis/trans) and absolute configuration made by Li et al. were at variance with our results. The above highly stereoselective syntheses of (+/-)-DB[a,l]P DE-2 adducted dAdo derivatives enabled efficient preparation of each of the four possible stereoisomeric 5'-dimethoxytrityl-3'-phosphoramidites for use in oligonucleotide synthesis.
Citation:
Chem. Res. Toxicol. 2008, 21 (12):2379-2392
Journal:
Chemical research in toxicology
Issue Date:
Dec-2008
URI:
http://hdl.handle.net/10146/84154
DOI:
10.1021/tx800268f
PubMed ID:
19053320
Additional Links:
http://pubs.acs.org/doi/abs/10.1021/tx800268f
Type:
Article
Language:
en
ISSN:
0893-228X
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorYagi, Haruhikoen
dc.contributor.authorFrank, Heinrichen
dc.contributor.authorSeidel, Albrechten
dc.contributor.authorJerina, Donald M.en
dc.date.accessioned2009-10-13T10:15:25Z-
dc.date.available2009-10-13T10:15:25Z-
dc.date.issued2008-12-
dc.identifier.citationChem. Res. Toxicol. 2008, 21 (12):2379-2392en
dc.identifier.issn0893-228X-
dc.identifier.pmid19053320-
dc.identifier.doi10.1021/tx800268f-
dc.identifier.urihttp://hdl.handle.net/10146/84154-
dc.description.abstractWe have reassigned relative and absolute configurations by unambiguous stereoselective syntheses of the cis- (13s and 13R) and trans-N6-deoxyadenosine (dAdo) adduct diastereomers (14S and 14R) derived from (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]P DE-2), previously reported by Li et al. [(1999) Chem. Res. Toxicol. 12, 758-767]. Two stereoselective methods, asymmetric aminohydroxylation of the (+/-)-trans-11,12-dihydrodiol (3) with 3',5'-di-O-(tert -butyldimethylsilyl)-2'-deoxyadenosine (4) and the highly stereoselective cis addition of 4 to (+/-)-DB[a,l]P DE-2 in hexafluoropropan-2-ol (HFP), were employed. Both afforded a 1:1 mixture of the cis-N6-dAdo adduct diastereomers, which were separated as triacetates (5S and 5R) in comparable yields (approximately 80%). The corresponding trans adduct diastereomers (10S and 10R) were obtained by coupling the aminotriol derived from trans opening of (+/-)-DB[a,l]P DE-2 with 6-fluoro-(2'-deoxy-3,5-di-tert-butyldimethylsilyloxy-beta-D-erythro-pentafuranosyl)purine (9) and subsequent acetylation in approximately 70% yield. The cis-5S and -5R and trans-10S and -10R were separately treated with 7% HF-pyridine followed by ammonolysis in NH3-saturated MeOH to give the dAdo adducts with all hydroxyl groups free (13S, 13R, 14S, and 14R). Comparison of the 1H NMR and CD spectra of these presently synthesized dAdo adducts with spectra of the previously reported compounds revealed that the interpretation of the 1H NMR and CD spectra and assignment of the relative stereochemistry (cis/trans) and absolute configuration made by Li et al. were at variance with our results. The above highly stereoselective syntheses of (+/-)-DB[a,l]P DE-2 adducted dAdo derivatives enabled efficient preparation of each of the four possible stereoisomeric 5'-dimethoxytrityl-3'-phosphoramidites for use in oligonucleotide synthesis.en
dc.language.isoenen
dc.relation.urlhttp://pubs.acs.org/doi/abs/10.1021/tx800268fen
dc.subjectCarcinogensen
dc.subjectDNA Adductsen
dc.subjectDeoxyadenosinesen
dc.subjectDihydroxydihydrobenzopyrenesen
dc.subjectEpoxy Compoundsen
dc.subjectMolecular Conformationen
dc.subjectStereoisomerismen
dc.subject.meshCarcinogens-
dc.subject.meshDNA Adducts-
dc.subject.meshDeoxyadenosines-
dc.subject.meshDihydroxydihydrobenzopyrenes-
dc.subject.meshEpoxy Compounds-
dc.subject.meshMolecular Conformation-
dc.subject.meshStereoisomerism-
dc.titleRevised assignment of absolute configuration of the cis- and trans-N6-deoxyadenosine adducts at C14 of (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene by stereoselective synthesis.en
dc.typeArticleen
dc.identifier.journalChemical research in toxicologyen
All Items in ECNIS-NIOM are protected by copyright, with all rights reserved, unless otherwise indicated.