Synthesis of 1- and 3-fluorobenzo[a]pyrene

Mulder, Patrick P.J.; Ramakrishna, N. V. S.; Cremonesi, Paolo; Rogan, Eleanor G.; Cavalieri, Ercole L.

doi:10.1021/tx00035a010

Cited by 7 publications

(2 citation statements)

References 10 publications

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“…The HPLC profile of the final product showed that it consisted of 68% ( R t = 18.3 min) 3-fluorobenzo[ a ]pyrene, 30% ( R t = 21.6 min) 1-fluorobenzo[ a ]pyrene, and 2% of the 6-fluoro isomer ( R t = 26.6 min) (Supporting Information, S1). These compounds were identified by comparison of retention times and the UV and 1 H NMR properties of independently prepared standard samples ( , ). The UV absorption profiles of the three isomers were generally similar except that the 6-fluoro isomer exhibited a significant red shift of absorptions centered on 280 nm (Supporting Information, S1).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Enantiomeric anti-2-Fluorobenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides and Their 2‘-Deoxyguanosine and Oligodeoxynucleotide Adducts

Yang

Huang

Cho

2006

Chem. Res. Toxicol.

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Benzo[a]pyrene diol epoxides (BPDEs) are the ultimate carcinogenic species of benzo[a]pyrene, a prototype polycyclic aromatic hydrocarbon (PAH). BPDE-modified DNA duplexes can adopt multiple conformations depending on the nature of the modified bases, the stereochemistry at the location of the covalent linkage, and the sequence context surrounding the lesion site. In this paper, we describe the preparation of enantiomeric 2-fluoro-BPDEs, trans-(7R,8S)-dihydroxy-(9S,10R)- and trans-(7S,8R)-(9R,10S)-epoxy-7,8,9,10-tetrtahydro-2-fluorobenzo[a]pyrene (22 and 23, respectively), as models for probing the BPDE-induced conformational heterogeneity. The multistep synthesis of the target diol epoxides described herein entails regiospecific succinoylation of 2-fluoropyrene, followed by a ring closure, regio- and stereospecific construction of the 7,8-dihydrodiol functionality, and a subsequent meta-chloroperbenzoic acid-mediated epoxidation. Stereoselectivity was achieved by using Jacobsen chiral catalysts, which produced greater than approximately 90% enantiomeric excess. Absolute configurations at the C(7,8) carbons of the FBP derivatives were determined by comparison of the circular dichroism (CD) spectra with those reported for the BP analogues. Analysis of the 3J(7,8) vicinal coupling constants, CD shape, and charge density calculations all indicated that the prepared anti-FBPDEs preferentially adopt the pseudo-diequatorial C(7,8) diol conformation. Hydrolysis of anti-FBPDEs produced a 9:1 ratio of trans- to cis-opened tetraols. Reactions of each of the anti-FBPDEs with deoxyguanosine 5'-monophosphate produced predominantly trans-anti-N2-dG as the major adducts. Analogous reactions with two 11-mer oligodeoxynucleotides (5'-CCATXGCTACC-3' where X = dT, dC) gave FBP-modified oligodeoxynucleotides with structures that were characterized by enzyme digest/HPLC and electrospray ionization time-of-flight mass spectrometry data. The oligonucleotide adducts were annealed with the appropriate sequences to form fully complementary duplexes [(5'-CCATXGCTACC-3')(5'-GGTAGCYATGG-3'), G = FBP-N2-dG adduct, X = dT, Y = dA in duplex I; X = dC, Y = dG in duplex II] for CD and UV melting studies. The results of the present study were consistent with those reported previously for BPDE-modified duplexes in the same sequence contexts and support the utility of FBPDEs as useful structural probes.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Enantiomeric anti-2-Fluorobenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides and Their 2‘-Deoxyguanosine and Oligodeoxynucleotide Adducts

Yang

Huang

Cho

2006

Chem. Res. Toxicol.

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“…Chlorination of 1 with copper( II ) chloride indeed succeeded in excellent yield,13 and the subsequent nitration gave rise to a 3:2 mixture of 6‐chloro‐1‐nitro‐ ( 3a ) and 6‐chloro‐3‐nitro‐ B[ a ]P ( 3b ). The difference in the polarities of the two isomers was indeed sufficient for separated spots to be obtained on TLC (silica, acetone/ n ‐hexane, 1/4, R f = 0.44 and 0.53).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 1‐ and 3‐Nitrobenzo[a]pyrene

2003

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Balz‐Schiemann Reaction

2010

Comprehensive Organic Name Reactions and Reagents

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In this reaction, a fluorine atom is introduced into aromatic rings through the thermal decomposition of diazonium tetrafluoroborate by diazotization of the corresponding aromatic amines. This reaction is generally known as the Balz–Schiemann reaction. This reaction is especially important for synthesizing the specifically fluorinated aromatic compounds, of which the decomposition in the absence of solvent normally affords a fairly good yield of aromatic fluorides. The Balz–Schiemann reaction has been extensively reviewed and has been found useful in the preparation of aromatic halides.

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Synthesis of 1- and 3-fluorobenzo[a]pyrene

Cited by 7 publications

References 10 publications

Synthesis and Characterization of Enantiomeric anti-2-Fluorobenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides and Their 2‘-Deoxyguanosine and Oligodeoxynucleotide Adducts

Synthesis and Characterization of Enantiomeric anti-2-Fluorobenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides and Their 2‘-Deoxyguanosine and Oligodeoxynucleotide Adducts

Synthesis of 1‐ and 3‐Nitrobenzo[a]pyrene

Balz‐Schiemann Reaction

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