A short, stereocontrolled, and practical synthesis of alpha-methylomuralide, a potent inhibitor of proteasome function.
An efficient and practical synthesis of alpha-methylomuralide (3), a selective inhibitor of proteasomes, has been developed as outlined in Scheme 1. Among the advantages of this route of synthesis over previously described approaches are (1) ease of scale-up and (2) high yields (28% overall yield of alpha-methylomuralide from 6) and stereocontrol (including high enantiocontrol). The synthesis is well suited to the production of 3 in the quantities needed for material-intensive in vivo investigations.
Saravanan
P
P
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Corey
E J
EJ
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003546:Cysteine Endopeptidases; D007202:Indicators and Reagents; D007769:Lactams / Q000737:chemistry; D007783:Lactones / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013237:Stereoisomerism
D007202:Indicators and Reagents; D007769:Lactams; D007783:Lactones; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; C477260:methylomuralide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex