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.
Liu
C
C
Department of Medicinal Chemistry, University of Michigan, Ann Arbor 48109.
Coward
J K
JK
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
C027548:S-adenosyl-3-thio-1,8-diaminooctane; D011436:Spermidine Synthase; D000241:Adenosine