Synthesis of deuterated γ-lactones for use in stable isotope dilution assays

Two syntheses of deuterated gamma-lactones for use as internal standards in stable isotope dilution assays (SIDA) were developed. [2,2,3,3-H-2(4)]-gamma-Octa-, -gamma-deca-, and -gamma-dodecalactones with > 89% deuterium incorporation were prepared in 27, 17, and 19% overall yields, respectively, by the reduction of a doubly protected hydroxypropiolic acid with deuterium gas. [3,3,4-H-2(3)]-gamma-Octa- and -gamma-dodecalactones were prepared in 6 and 23% yields with > 92% deuterium incorporation by the free radical addition of 2-iodoacetamide to [1,1,2-H-2(3)]-1-hexene and [1,1,2-H-2(3)]-1-decene, respectively. Reaction yields were highly dependent upon the purity of the 1-alkene starting material. The deuterated gamma-lactones were evaluated as internal standards for SIDA.