421556-73-2

Upstream product

• 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 
• 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 
• 421556-70-9 (S)-4-[7-[2-Benzyloxy-5-((S)-2-benzyloxycarbonylamino-2-methoxycarbonyl-ethyl)-phenyl]-2-oxo-1,2-dihydro-indol-(3E)-ylidenemethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 421556-69-6 (S)-N-benzyloxycarbonyl-3-(4-benzyloxy-3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl)alanine methyl ester 
• 421556-68-5 (S)-N-benzyloxycarbonyl-3-(4-benzyloxy-3-iodophenyl)alanine methyl ester 
• 421556-67-4 4-(7-iodo-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 421556-66-3 4-(7-iodo-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 119140-66-8 N-Cbz-O-benzyl-L-tyrosine methyl ester 
• 108149-60-6 methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate 
• 60-18-4 L-tyrosine 
• 95715-87-0 (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine 
• 13512-31-7 N-(benzyloxycarbonyl)-L-tyrosine methyl ester 
• 25456-86-4 L-asparagine tert-butyl ester 
• 1080-06-4 L-Tyr-OMe 

Downstream Products

• 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 
• 262854-05-7 TMC-95A 
• 262854-05-7 TMC-95B 

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.

The total synthesis of proteasome inhibitors TMC-95A and TMC-95B: Discovery of a new method to generate cis-propenyl amides

Silatropic and ene-like bond reorganizations (see scheme, left) were the key steps in the first total synthesis of the title compounds, which only differ in stereochemistry at the remote C36 stereocenter. Other key steps include a Suzuki biaryl construction, a diastereofacial dihydroxylation reaction, and a macrolactamization.