Synthesis of a C8 OTA-dG adduct and incorporation into DNA

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Paugh, Robert John
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University of Guelph

This thesis is an investigion into a synthetic methodology that was developed to yield a brominated ochratoxin A analogue. The regioselective bromination was unambiguously confirmed through NMR experiments. An OTA nucleoside adduct analogue bearing the same structural features of the C8 OTA-dG adduct was successfully synthesized utilizing a Suzuki coupling procedure to afford the analogue in moderate yields. Possessing similar chemical properties and structural components, this adduct was used in a series of experiments utilizing the photochemical absorption and emission properties involving an excited state intramolecular proton transfer process in which a neighbouring carbonyl group is necessary to effect the excited state proton transfer process. Other structurally relevant analogues were synthesized accordingly to further elucidate the properties of such compounds. The chemical nature of the lactone ring in ochratoxin A hindered attempts to successfully synthesize the boronate ester, which was required to obtain the OTA-dG adduct synthetically.

C8 OTA-dG adduct, DNA, brominated ochratoxin A analogue, Suzuki coupling procedure, boronate ester