Stereocontrolled synthesis of the northern part of potent proteasome inhibitor TMC-95A.
[reaction: see text]. A protected version of the northern part of TMC-95A, a potent and selective proteasome inhibitor, was synthesized with full stereochemical control. Highlights of this synthesis include (i) a (Z)-selective Mizoroki-Heck reaction to construct the oxyindole portion, (ii) a diastereoselective epoxidation, (iii) a 6-endo selective epoxide opening by Boc carbonyl group to establish the stereochemistry of C6, and (iv) a 1,3-elimination reaction of the L-allo-threonine derivative under Mitsunobu conditions to afford the (Z)-1-propenylamine.
Inoue
M
M
Department of Chemistry, Graduate School of Science, Tohoku University, and CREST, Japan Science and Technology Corporation (JST), Sendai 980-8578, Japan.
Furuyama
H
H
Sakazaki
H
H
Hirama
M
M
D003546:Cysteine Endopeptidases; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex
D009097:Multienzyme Complexes; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; C408291:TMC-95A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex