Ovine Metabolism of Lithogenic Sapogenins. Synthesis of [2,2,4,4-2H4]Sarsasapogenone, [2,2,4,4-2H4]Sarsasapogenin, and [2,2,4,4-2H4]Episarsasapogenin and Evaluation of Deuterium Retention in a Sheep-Dosing Trial

The suitability of [2,2,4,4-2H4]sarsasapogenone (1b), [2,2,4,4-2H4]sarsasapogenin (2b), and [2,2,4,4-2H4]episarsasapogenin (3b) as isotopically labeled dosing substrates to determine the levels of free and conjugated sapogenins present in feces from sheep grazing saponin-containing plants implicated in the development of ovine heptagenous photosentization diseases was investigated. A 1:4 mixture of [2,2,4,4-2H4]sarsasapogenin (2b) and [2,2,4,4-2H4]episarsasapogenin (3b), obtained by reduction of [2,2,4,4-2H4]sarsasapogenone (1b), was found to retain 94% of incorporated deuterium, when dosed to one sheep. The recovery of the dosed mixture of genins 2b and 3b was calculated to be 85%. Considerable loss of deuterium and a lower recovery of genin material were observed when [2,2,4,4-2H4]sarsasapogenone (1b) was dosed. Keywords: Deuterated sapogenins; dosing trial; sheep; fecal material; Narthecium ossifragum; episarsasapogenin; sarsasapogenin; sarsasapogenone