368872-48-4

Upstream product

• 608-30-0 2,6-dibromoaniline 
• 129483-65-4 (4S)-1,1-Dimethylethyl 4-<(E)-3'-methoxy-3'-oxo-1'-propenyl>-2,2-dimethyl-3-oxazolidinecarboxylate 
• 108149-60-6 methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate 
• 95715-87-0 (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine 

Downstream Products

• 368872-57-5 C₂₄H₂₂BrN₃O₉ 
• 368872-58-6 C₂₃H₂₀BrN₃O₉ 
• 368872-54-2 C₂₀H₂₂O₇N₂BrCOC₆H₅ 
• 368872-56-4 C₁₉H₁₃BrN₂O₇ 
• 368872-55-3 C₁₉H₁₅BrN₂O₆ 
• 368872-49-5 4-{3-[tert-butoxycarbonyl-(2,6-dibromo-phenyl)-amino]-3-oxo-propenyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR

A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an α-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.

Synthesis of the functionalized macrocyclic core of proteasome inhibitors TMC-95A and B

An ordered assembly of four building blocks (2-5) forms the basis of the synthesis of 1, which contains the core structure of TMC-95A and B - two potent proteasome inhibitore (see scheme; TIPS = triisopropylsilyl, Cbz = benzoxycarbonyl, Boc = tert-Boc = tert-butoxycarbonyl).

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.