STEREOSPECIFIC SYNTHESIS OF (R)-S-ADENOSYL-1,8-DIAMINO-3-THIOOCTANE 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 (> 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 > 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.