Synthesis of polycyclic aromatic hydrocarbon modified 2 prime -deoxyadenosine analogs and the first fjord region tetrahydroepoxide

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:6318841

Lakshman, M

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental contaminants, which can be metabolized to carcinogens. Research in this field has shown that the diol epoxides are the metabolites of these PAH that are responsible for carcinogenic activity. These metabolites generally possess a sterically hindered bay or fjord region. In an effort at understanding the structural requirements of these fjord region PAH, we have synthesized the fjord region tetrahydroepoxide of benzo(g)chrysene. The compound described in this dissertation is expected to be more biologically active as compared to the diol epoxide in the same tetrahydro ring. PAH diol epoxides are known to intercalate and bind covalently to DNA. Evidence suggests that binding of these diol epoxides to DNA causes mutations. However, the exact mechanism of carcinogenesis at the molecular level is as yet unknown. This led us to the synthesis of PAH substituted nucleosides. These nucleosides could be incorporated into oligonucleotides and used for site directed mutagenesis. The effect of PAH diol epoxide binding on DNA conformation could also be probed. This dissertation, therefore, describes the initial efforts in the synthesis of these PAH substituted mononucleosides. The synthetic scheme involved synthesis of activated purine nucleosides and the appropriately substituted PAH derivative. Finally two PAH substituted 2{prime}-deoxyadenosine analogs (naphthalene and benzo(a)pyrene), were synthesized.

• Research Organization: Oklahoma Univ., Norman, OK (USA)
• OSTI ID: 6318841
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AROMATICS
BENZOPYRENE
BIOSYNTHESIS
CARCINOGENESIS
CONDENSED AROMATICS
DNA ADDUCTS
HYDROCARBONS
METABOLISM
METABOLITES
NAPHTHALENE
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
PATHOGENESIS
POLYCYCLIC AROMATIC HYDROCARBONS
RIBOSIDES
SYNTHESIS