180973-35-7

Basic information

• Product Name: (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone
• Synonyms: (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone
• CAS NO: 180973-35-7
• Molecular Weight: 1027.36
• Mol File: 180973-35-7.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone(CAS DataBase Reference)
• NIST Chemistry Reference: (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone(180973-35-7)
• EPA Substance Registry System: (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone(180973-35-7)

Safety Data

• Hazardous Substances Data: 180973-35-7(Hazardous Substances Data)

Upstream product

• 2409-87-2 methyl (2E)-penta-2,4-dienoate 
• 180973-40-4 (E)-(S)-3-Hydroxy-7-tritylsulfanyl-hept-4-enoic acid benzyl ester 
• 180973-41-5 (E)-(R)-3-Hydroxy-7-tritylsulfanyl-hept-4-enoic acid benzyl ester 
• 180973-24-4 (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid 
• 180973-26-6 (R,E)-3-hydroxy-7-(tritylthio)hept-4-enoic acid 
• 181141-24-2 (5E,7R,11R,14S,17E,20S)-methyl 17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oate 
• 180973-33-5 (5E,7S,11R,14S,17E,20S)-methyl 17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oate 
• 180973-31-3 (S)-2-[(2S,3R)-2-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-methyl-butyrylamino]-3-tritylsulfanyl-propionylamino}-3-(toluene-4-sulfonyloxy)-butyrylamino]-3-methyl-butyric acid methyl ester 
• 180973-30-2 (S)-2-((2S,3R)-2-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-methyl-butyrylamino]-3-tritylsulfanyl-propionylamino}-3-hydroxy-butyrylamino)-3-methyl-butyric acid methyl ester 
• 180973-28-8 (S)-2-{(2S,3R)-2-[(S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanyl-propionylamino]-3-hydroxy-butyrylamino}-3-methyl-butyric acid methyl ester 
• 180973-32-4 (S)-2-{(Z)-2-[(S)-2-((R)-2-Amino-3-methyl-butyrylamino)-3-tritylsulfanyl-propionylamino]-but-2-enoylamino}-3-methyl-butyric acid methyl ester 
• 180973-42-6 N-[(9-fluorenylmethoxy)carbonyl]-L-threonyl-L-valine methyl ester 
• 180973-36-8 (E)-5-Tritylsulfanyl-pent-2-enoic acid methyl ester 
• 180973-37-9 (E)-5-(tritylthio)-2-penten-1-ol 

Downstream Products

• 128517-07-7 romidepsin 

Relevant articles and documents

Total synthesis of the bicyclic depsipeptide hdac inhibitors spiruchostatins a and b, 5″-epi-spiruchostatin b, fk228 (fr901228) and preliminary evaluation of their biological activity

The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins A and B, 5″-ep(-spiruchostatin B and FK228 were efficiently synthesized in a convergent and unified manner. The synthetic method involved the following crucial steps : i) a JuliaKocienski olefination of a 1,3-propanediol-derived sulfone and a L- or Dmalic acid-derived aldehyde to access the most synthetically challenging unit, (35 or 3R,4E)-3-hydroxy-7- mercaptohept-4-enoic acid, present in a D-alanine- or D-valine-containing segment; ii) a condensation of a D-valine-D-cysteine- or D-allo-isoleucine-D- cysteinecontaining segment with a D-alanineor D-valine-containing segment to directly assemble the corresponding secoacids; and iii) a macrocyclization of a seco-acid using the Shiina method or the Mitsunobu method to construct the requisite 15- or 16-membered macrolactone. The present synthesis has established the C5″ stereochemistry of spiruchostatin B. In addition, HDAC inhibitory assay and the cell-growth inhibition analysis of the synthesized depsipeptides determined the order of their potency and revealed some novel aspects of structure-activity relationships. It was also found that unnatural 5″-epi-spiruchostatin B shows extremely high selectivity (ca. 1600-fold) for class I HDAC1 (IC50 = 2.4 nM) over class II HDAC6 (IC 50 = 3900nM) with potent cell-growth-inhibitory activity at nanomolar levels of IC50 values.

Macrolactamization versus macrolactonization: Total synthesis of FK228, the depsipeptide histone deacetylase inhibitor

(Chemical Equation Presented) The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials as an anticancer agent. While currently obtained by fermentation, total synthesis is an attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.