262854-05-7

Basic information

• Product Name: (10S,11R,12S,15S,18S)-15-(Carbamoylmethyl)-10,11,23-trihydroxy-18-[3(R)-methyl-2-oxopentanamido]-9,14,17-trioxo-N-[1(Z)-propenyl]-8,13,16-triazatetracyclo[18.3.1.0(2,7).0(6,10)]tetracosa-1(24),2,4,6,20,22-hexaene-12-carboxamide
• Synonyms: TMC-95B; (3S,7S,15S,18S,21S,22R)-2,3-Dihydro-3,13,22-trihydroxy-15-[3(R)-methyl-1,2-dioxopentylamino]-2,16,19-trioxo-21-[1(Z)-propenylaminocarbonyl]-,7,3-([1,3]benzenopropaniminoethaniminoethano)-1H-indole-18-acetamide
• CAS NO: 262854-05-7
• Molecular Formula: C₃₃H₃₈N₆O₁₀
• Molecular Weight: 678.70501
• Mol File: 262854-05-7.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: (10S,11R,12S,15S,18S)-15-(Carbamoylmethyl)-10,11,23-trihydroxy-18-[3(R)-methyl-2-oxopentanamido]-9,14,17-trioxo-N-[1(Z)-propenyl]-8,13,16-triazatetracyclo[18.3.1.0(2,7).0(6,10)]tetracosa-1(24),2,4,6,20,22-hexaene-12-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: (10S,11R,12S,15S,18S)-15-(Carbamoylmethyl)-10,11,23-trihydroxy-18-[3(R)-methyl-2-oxopentanamido]-9,14,17-trioxo-N-[1(Z)-propenyl]-8,13,16-triazatetracyclo[18.3.1.0(2,7).0(6,10)]tetracosa-1(24),2,4,6,20,22-hexaene-12-carboxamide(262854-05-7)
• EPA Substance Registry System: (10S,11R,12S,15S,18S)-15-(Carbamoylmethyl)-10,11,23-trihydroxy-18-[3(R)-methyl-2-oxopentanamido]-9,14,17-trioxo-N-[1(Z)-propenyl]-8,13,16-triazatetracyclo[18.3.1.0(2,7).0(6,10)]tetracosa-1(24),2,4,6,20,22-hexaene-12-carboxamide(262854-05-7)

Safety Data

• Hazardous Substances Data: 262854-05-7(Hazardous Substances Data)

Upstream product

• 60-18-4 L-tyrosine 
• 86942-76-9 N-1-triethylsilylprop-2-en-1-ylamine 
• 31676-49-0 7-iodooxindole 
• 602301-47-3 C₆₁H₇₅N₅O₁₅Si 
• 602301-49-5 (S)-2-{(S)-3-(3-{(S)-3-[(2R,4R,5R)-5-Amino-2-(4-methoxy-phenyl)-[1,3]dioxan-4-yl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl}-4-methoxymethoxy-phenyl)-2-[(2S,3S)-2-(tert-butyl-dimethyl-silanyloxy)-3-methyl-pentanoylamino]-propionylamino}-butaoic acid 
• 602301-46-2 3-(3-{3-[5-benzyloxycarbonylamino-2-(4-methoxy-phenyl)-[1,3]dioxan-4-yl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-7-yl}-4-methoxymethoxy-phenyl)-2-[2-(tert-butyl-dimethyl-silanyloxy)-3-methyl-pentanoylamino]-propionic acid methyl ester 
• 602301-45-1 (S)-2-[(2S,3S)-2-(tert-Butyl-dimethyl-silanyloxy)-3-methyl-pentanoylamino]-3-[4-methoxymethoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionic acid methyl ester 
• 602301-42-8 [(2R,4R,5R)-4-((S)-3-Hydroxy-7-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-2-(4-methoxy-phenyl)-[1,3]dioxan-5-yl]-carbamic acid benzyl ester 
• 602301-44-0 (S)-2-[(2S,3S)-2-(tert-Butyl-dimethyl-silanyloxy)-3-methyl-pentanoylamino]-3-(3-iodo-4-methoxymethoxy-phenyl)-propionic acid methyl ester 
• 602301-48-4 (S)-2-((2S,3S)-2-Hydroxy-3-methyl-pentanoylamino)-3-(3-iodo-4-methoxymethoxy-phenyl)-propionic acid methyl ester 

Relevant articles and documents

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.