Solvent-free synthesis of benzo[a]pyrene 7,8-diol 9,10-epoxide adducts at the N(2)-position of deoxyguanosine.
[reaction: see text] The first solid-state (or solvent-free) synthesis of protected deoxyguanosine (dG) adducts of benzo[a]pyrene diol epoxides at room temperature is reported. Whereas dG adducts derived from cis- and trans-opening of (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-1 1) are formed as a 1:1 mixture, the direct opening of the diastereomeric (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-2, 2) produced a 15:85 ratio favoring the trans-opened dG adduct 7.
Ramesha
A R
AR
Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, Maryland 20892, USA.
Kroth
H
H
Jerina
D M
DM
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D018736:DNA Adducts / Q000138:chemical synthesis* / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018736:DNA Adducts; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C040060:7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine; D003849:Deoxyguanosine