Fluoro Alcohol Mediate Displ C10 Acetoxy Benzo[a]pyrene-7,8,9,10-tetrahydrotetrol Tetraacetate: New Route to Diol Epoxide-Deoxyguanosine Adduct

Abstract

Trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) mediated sub rxn of the bay-region C10 acetoxy group in 4 stereoisomeric 7,8,9,10-tetraacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (tetraol tetraacetate, two pair of cis & trans isomers at 9,10 positions) by the exocyclic N2-amino group of O6-allyl-3',5'-di-O-(TBDMS)-2'-deoxyguanosine (3). The tetraacetate are derived from cis & trans hydrolysis of (±)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (±)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10 followed by acetylation. Excellent y and high regioselectivity were observed. Similar cis/trans product ratios were observed for each set of cis and trans tetraol tetraacetates derived from DE-1 (~75/25) and from DE-2 (~67/33) in HFP. This strongly suggests that the sub proceeds via an SN1 mech involving a carbocation int common to the cis & trans tetraacetate. Since it is likely that the cis and trans products from 3 arise from different conformations of the carbocation, its lifetime must be sufficiently long to permit conformational equilibration before its capture by the purine nucleophile. Corresponding rxn of (±)-9-bromo-7,8,10-triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in HFP was highly regio- and stereoselective and gave exclusively trans 10-adducts. This newly developed sub rxn provides an attractive alt synth oligonucleotide PAH adduct synthon.