Stereospecific synthesis of (R)- and (S)-S-adenosyl-1,8-diamino-3-thiooctane, a potent inhibitor of polyamine biosynthesis. Comparison of asymmetric induction vs enantiomeric synthesis.

Two diastereomers of the potent spermidine synthase inhibitor S-adenosyl-1,8-diamino-3-thiooctane have been prepared in high (greater than 96% de) stereochemical purity. Two synthetic routes were investigated, one based on asymmetric induction and the other involving an enantiomeric synthesis. The latter route gave the desired products in greater than 96% de, whereas the synthesis based on asymmetric induction resulted in only 80% de in the final product. Evaluation of the two diastereomers as inhibitors of spermidine synthase showed that the R diastereomer is a more potent inhibitor than the S diastereomer.