Synthesis of [3,3-D2]4-hydroxy-1-(3-pyridyl)-1-butanone, an internal standard for analysis of tobacco-specific nitrosamine hemoglobin and DNA adducts

The synthesis of [3, 3-D2]4-hydroxy-1-(3-pyridyl)-1-butanone ([3, 3-D2]HPB), an internal standard for the analysis of hemoglobin and DNA adducts of tobacco-specific nitrosamines, is reported. 3-Pyridine carboxaldehyde was converted to 2-(3-pyridyl)-1, 3-dithiane. This was condensed with 2-(2-bromoethyl)-1, 3-dioxalane to yield 2-[2-(3-pyridyl)-1, 3-dithiane]ethyl-1, 3-dioxalane. Selective hydroylsis of the aldehyde protecting group produced 4-(1, 3-dithian-2-yl)-4-(3-pyridyl)-butanal, which was then labeled with deuterium adjacent to the aldehyde carbonyl group. Reduction with LiA1H4 produced the corresponding alcohol. Removal of the dithianyl protecting group required protection of the alcohol as its t-butyldimethyl-silyl ether. Treatment with AgNO3/N-chlorosuccin-imide in aqueous CH3CN produced [3, 3-D2]HPB. (author)