1043577-34-9

Basic information

• Product Name: (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro[2,4'-bithiazole]-4-carboxamido)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate
• Synonyms: (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro[2,4'-bithiazole]-4-carboxamido)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate
• CAS NO: 1043577-34-9
• Molecular Weight: 957.364
• Mol File: 1043577-34-9.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro[2,4'-bithiazole]-4-carboxamido)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate(CAS DataBase Reference)
• NIST Chemistry Reference: (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro[2,4'-bithiazole]-4-carboxamido)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate(1043577-34-9)
• EPA Substance Registry System: (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((R)-2'-(((tert-butoxycarbonyl)amino)methyl)-4-methyl-4,5-dihydro[2,4'-bithiazole]-4-carboxamido)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate(1043577-34-9)

Safety Data

• Hazardous Substances Data: 1043577-34-9(Hazardous Substances Data)

Upstream product

• 1043577-28-1 (3S)-hydroxy-1-((4R)-benzyl-2-thioxothiazolidin-3-yl)-7-tritylsulfanylhept-(4E)-en-1-one 
• 150350-28-0 S-trityl 3-mercaptopropionaldehyde 
• 3695-77-0 triphenylmethanethiol 
• 180973-22-2 (2E)-5-[(triphenylmethyl)thio]-2-pentenal 
• 96929-05-4 ethyl 2-[N-(tert-butoxycarbonyl)aminomethyl]thiazole-4-carboxylate 
• 1089192-66-4 (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl) amino)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate 
• 68858-20-8 Fmoc-Val-OH 
• 1043577-31-6 (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-amino-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate 
• 182120-82-7 2-(tert-butoxycarbonylaminomethyl)-1,3-thiazole-4-carboxamide 
• 89226-13-1 2-(N-t-butoxycarbonylamino)thioacetamide 
• 71904-80-8 2-((tert-butoxycarbonylamino)methyl)thiazole-4-carboxylic acid 
• 35150-09-5 N-(tert-butoxycarbonyl)glycine 
• 297165-32-3 methyl 2-(tert-butoxycarbonylaminomethyl)thiazole-4-carboxylate 
• 1033814-13-9 (R)-2-(2-((tert-butoxycarbonylamino)methyl)thiazol-4-yl)-4-methyl-4,5-dihydrothiazole-4-carboxylic acid 

Downstream Products

• 1009815-87-5 largazole 
• 1043577-37-2 (5R,8S,11S)-8-isopropyl-5-methyl-11-((E)-4-(tritylthio)but-1-en-1-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.12,5]icosa-1⁽¹⁸⁾,2⁽²⁰⁾,16⁽¹⁹⁾-triene-6,9,13-trione 

Relevant articles and documents

Total synthesis and biological mode of action of largazole: A potent class I histone deacetylase inhibitor

The efficient total synthesis of the recently described natural substance largazole (1) and its active metabolite largazole thiol (2) is described. The synthesis required eight linear steps and proceeded in 37% overall yield. It is demonstrated that largazole is a pro-drug that is activated by removal of the octanoyl residue from the 3-hydroxy-7-mercaptohept-4-enoic acid moiety to generate the active metabolite 2, which is an extraordinarily potent Class I histone deacetylase inhibitor. Synthetic largazole and 2 have been evaluated side-by-side with FK228 and SAHA for inhibition of HDACs 1, 2, 3, and 6. Largazole and largazole thiol were further assayed for cytotoxic activity against a panel of chemoresistant melanoma cell lines, and it was found that largazole is substantially more cytotoxic than largazole thiol; this difference is attributed to differences in the cell permeability of the two substances.

Design, synthesis, and biological evaluation of largazole derivatives: Alteration of the zinc-binding domain

A new series of largazole analogues in which the side chain was replaced with disulfide groups were synthesized, and their biological activities were evaluated. Compound 8 bearing an octyl moiety showed much better selectivity for HDAC1 over HDAC7 than largazole (320-fold). Structure-activity relationships suggested that the length in the disulfide chain of largazole is important for the selectivity toward HDAC1 over HDAC7.

Method for preparing largazole analogs and uses thereof

Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.