31676-49-0

Upstream product

• 117500-16-0 2'-hydroxyimino-2-iodoacetanilide 
• 615-43-0 2-iodophenylamine 
• 20780-78-3 7-iodoisatin 

Downstream Products

• 353520-92-0 2-(2-benzyloxycarbonylamino-3-{3-[3-(2-tert-butoxycarbonylamino-1-hydroxy-3-triisopropylsilanyloxy-propyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-propionylamino)-succinamic acid tert-butyl ester 
• 353520-93-1 2-(2-benzyloxycarbonylamino-3-{3-[3-(2-tert-butoxycarbonylamino-1-hydroxy-3-triisopropylsilanyloxy-propyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-propionylamino)-succinamic acid tert-butyl ester 
• 353520-90-8 2-(2-benzyloxycarbonylamino-3-{3-[3-(2-tert-butoxycarbonylamino-3-triisopropylsilanyloxy-propylidene)-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-propionylamino)-succinamic acid tert-butyl ester 
• 1054636-07-5 (S)-2-((S)-3-{3-[(S)-3-((1R,2R)-2-Amino-1-hydroxy-3-triisopropylsilanyloxy-propyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-2-benzyloxycarbonylamino-propionylamino)-succinamic acid 
• 353520-94-2 2-(2-benzyloxycarbonylamino-3-{3-[3-(2-tert-butoxycarbonylamino-3-hydroxy-propylidene)-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-propionylamino)-succinamic acid tert-butyl ester 
• 353520-95-3 2-benzyloxycarbonylamino-3-{3-[3-(2-tert-butoxycarbonylamino-3-triisopropylsilanyloxy-propylidene)-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-propionic acid methyl ester 
• 353520-86-2 2-benzyloxycarbonylamino-3-{3-[3-(2-tert-butoxycarbonylamino-3-triisopropylsilanyloxy-propylidene)-2-oxo-2,3-dihydro-1H-indol-7-yl]-4-methoxy-phenyl}-propionic acid methyl ester 
• 262854-05-7 TMC-95B 
• 421556-74-3 2-(3-{4-benzyloxy-3-[3-(2-tert-butoxycarbonylamino-1-hydroxy-3-triisopropylsilanyloxy-propyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-phenyl}-2-benzyloxycarbonylamino-propionylamino)-succinamic acid tert-butyl ester 
• 421556-72-1 4-[(7-{2-benzyloxy-5-[2-benzyloxycarbonylamino-2-(1-tert-butoxycarbonyl-2-carbamoyl-ethylcarbamoyl)-ethyl]-phenyl}-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-hydroxy-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 421556-73-2 2-(3-{4-benzyloxy-3-[3-(2-tert-butoxycarbonylamino-1,3-dihydroxy-propyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl]-phenyl}-2-benzyloxycarbonylamino-propionylamino)-succinamic acid tert-butyl ester 
• 421556-71-0 (S)-4-[7-{2-Benzyloxy-5-[(S)-2-benzyloxycarbonylamino-2-((S)-1-tert-butoxycarbonyl-2-carbamoyl-ethylcarbamoyl)-ethyl]-phenyl}-2-oxo-1,2-dihydro-indol-(3E)-ylidenemethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 262854-05-7 TMC-95A 
• 709037-80-9 (S)-4-[7-[2-Benzyloxy-5-((S)-2-benzyloxycarbonylamino-2-carboxy-ethyl)-phenyl]-2-oxo-1,2-dihydro-indol-(3E)-ylidenemethyl]-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).