62697-13-6Relevant articles and documents
Synthesis and hydrolysis of a cis-chlorohydrin derived from a benzo[a]pyrene 7,8-diol 9,10-epoxide
Doan, Lanxuan,Yagi, Haruhiko,Jerina, Donald M.,Whalen, Dale L.
, p. 8012 - 8017 (2004)
(±)-7β,8α-Dihydroxy-9β,10β-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (DE-1) undergoes reaction with anhydrous HCl in dioxane to yield predominantly (～94%) a single chlorohydrin. This chlorohydrin was assigned structure 9, in which the chloro goup at C-10 is located cis to the C-9 hydroxyl group, on the basis of its 1H NMR spectrum. This result is in contrast to the reaction of a diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxide (DE-2) with HCl, which yields only transchlorohydrin 8. The hydrolysis of cis-chlorohydrin 9 in 10:90 dioxane - water solutions yields the same ratio of tetrols (～89% cis/11% trans) as that formed by acid-catalyzed hydrolysis of DE-1. This result again contrasts with the hydrolysis of trans-chlorohydrin 8, which undergoes hydrolysis to give tetrols in a ratio different from that from acid-catalyzed hydrolysis of DE-2. A marked common ion rate depression in the hydrolysis of cis-chlorohydrin 9 is observed, which shows that hydrolysis proceeds via an intermediate carbocation that has a sufficient lifetime to be trapped by external chloride ion. The observation that DE-1 reacts with HCl to give mainly the cis-chlorohydrin is rationalized by quantum chemical calculations that suggest that the cis-chlorohydrin is more stable than the epimeric trans-chlorohydrin.
Fluorinated alcohol mediated displacement of the C10 acetoxy group of benzo[a]pyrene-7,8,9,10-tetrahydrotetraol tetraacetates: A new route to diol epoxide-deoxyguanosine adducts
Yagi, Haruhiko,Jerina, Donald M.
, p. 9983 - 9990 (2008/03/28)
(Chemical Equation Presented) We describe a novel trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) mediated substitution reaction of the bay-region C10 acetoxy group in four stereoisomeric 7,8,9,10-tetraacetoxy-7,8,9, 10-tetrahydrobenzo[a]pyrenes (tetraol tetraacetates, two pairs of cis and trans isomers at the 9,10 positions) by the exocyclic N2-amino group of O6-allyl-3′,5′-di-O-(tert-butyldimethylsilyl)-2′- deoxyguanosine (3). The tetraacetates are derived from cis and trans hydrolysis of (±)-7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (±)-7β,8α- dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10 followed by acetylation. Excellent yields 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 substitution proceeds via an SN1 mechanism involving a carbocation intermediate that is common to the cis and trans tetraacetates. 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. The corresponding reaction of (±)-9α-bromo-7β,8α,10β- triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in HFP was highly regio- and stereoselective and gave exclusively trans 10β-adducts. This newly developed substitution reaction provides an attractive alternative synthetic strategy for the preparation of polycyclic hydrocarbon adducted oligonucleotide building blocks.
Chloride ion catalyzed conformational inversion of carbocation intermediates in the hydrolysis of a benzo[a]pyrene 7,8-diol 9,10-epoxide
Doan, Lanxuan,Yagi, Haruhiko,Jerina, Donald M.,Whalen, Dale L.
, p. 14382 - 14387 (2007/10/03)
A highly efficient procedure for converting 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (1) to its trans-9,10-chlorohydrin (5) with excellent yield and purity by the reaction of anhydrous HCI in THF has been developed. The rate of reac
