Regioisomeric synthesis and characteristics of the alpha-hydroxy-1,N(2)-propanodeoxyguanosine.
Acrolein, a known mutagen, undergoes reaction in vitro under physiological conditions with both 2'-deoxyguanosine and native DNA to give rise to exocyclic adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having a hydroxyl group at either the 6 or the 8 position (these positions are respectively designated alpha and gamma when referring to the 1,N(2)-(propano-bridge). Previously, we have shown that the 8-hydroxy derivative has very low mutagenicity probably because, in double-stranded DNA, this residue exists in the open-chain aldehydic form [N(2)-(3-oxopropyl)-2'-deoxyguanosine] (5). To continue our investigation in this area, we needed ample supplies of the 6-hydroxy isomers. This current paper describes high-yield simple methods for the synthesis in bulk of the 6-hydroxy and the 6-methoxy exocyclic adducts 1 and 3 and a new efficient synthesis of 1,N(2)()-(prop-1,3-diyl)-2'-deoxyguanosine (4), previously used as a chemically stable model in studying the physico-biological implications of 1,N(2) exocyclic adduction to dG.
Huang
Yanhe
Y
Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Johnson
Francis
F
D000171:Acrolein / Q000031:analogs & derivatives / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*
C452228:hydroxy-1,N(2)-propanodeoxyguanosine; D000171:Acrolein; D003849:Deoxyguanosine