166169-07-9

Upstream product

• 34914-36-8 2-(triphenylmethylthio)ethanoic acid 
• 1117-97-1 N,0-dimethylhydroxylamine 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 3695-77-0 triphenylmethanethiol 
• 134833-83-3 2-bromo-N-methoxy-N-methyl-acetamide 
• 1727-15-7 trityl thioacetic acid 

Downstream Products

• 186602-92-6 4-Methyl-2-(2-tritylsulfanyl-acetyl)-pentanoic acid methyl ester 
• 186602-56-2 Methyl-2-n-Heptyl-4-Tritylthio Acetoacetate 
• 186603-15-6 5-Phenyl-2-(2-tritylsulfanyl-acetyl)-pentanoic acid methyl ester 
• 166169-08-0 2-(triphenylmethylsulfanyl)acetaldehyde 
• 186602-79-9 2-(1-Hydroxy-2-tritylsulfanyl-ethyl)-5-phenyl-pentanoic acid ((S)-2-cyclohexyl-1-phenethylcarbamoyl-ethyl)-amide 
• 186603-27-0 2-(1-Hydroxy-2-tritylsulfanyl-ethyl)-5-phenyl-pentanoic acid [(S)-1-((S)-1-ethylcarbamoyl-3-methyl-butylcarbamoyl)-3-methyl-butyl]-amide 
• 186602-85-7 5-Phenyl-2-(2-tritylsulfanyl-acetyl)-pentanoic acid ((S)-2-cyclohexyl-1-phenethylcarbamoyl-ethyl)-amide 
• 186602-74-4 5-Phenyl-2-(2-tritylsulfanyl-acetyl)-pentanoic acid [(S)-1-((S)-1-ethylcarbamoyl-3-methyl-butylcarbamoyl)-3-methyl-butyl]-amide 
• 186603-04-3 2-(1-Hydroxy-2-tritylsulfanyl-ethyl)-nonanoic acid ((S)-2-cyclohexyl-1-phenethylcarbamoyl-ethyl)-amide 

Relevant academic research and scientific papers

Features of Auxiliaries That Enable Native Chemical Ligation beyond Glycine and Cleavage via Radical Fragmentation

Native chemical ligation (NCL) is an invaluable tool in the total chemical synthesis of proteins. Ligation auxiliaries overcome the requirement for cysteine. However, the reported auxiliaries remained limited to glycine-containing ligation sites and the acidic conditions applied for cleavage of the typically applied N-benzyl-type linkages promote side reactions. With the aim to improve upon both ligation and cleavage, we systematically investigated alternative ligation scaffolds that challenge the N-benzyl dogma. The study revealed that auxiliary-mediated peptide couplings are fastest when the ligation proceeds via 5-membered rather than 6-membered rings. Substituents in α-position of the amine shall be avoided. We observed, perhaps surprisingly, that additional β-substituents accelerated the ligation conferred by the β-mercaptoethyl scaffold. We also describe a potentially general means to remove ligation auxiliaries by treatment with an aqueous solution of triscarboxyethylphosphine (TCEP) and morpholine at pH 8.5. NMR analysis of a 13C-labeled auxiliary showed that cleavage most likely proceeds through a radical-triggered oxidative fragmentation. High ligation rates provided by β-substituted 2-mercaptoethyl scaffolds, their facile introduction as well as the mildness of the cleavage reaction are attractive features for protein synthesis beyond cysteine and glycine ligation sites.

Sulfur-Switch Ugi Reaction for Macrocyclic Disulfide-Bridged Peptidomimetics

A general strategy is introduced for the efficient synthetic access of disulfide linked artificial macrocycles via a Ugi four-component reaction (U4CR) followed by oxidative cyclization. The double-mercapto input is proposed for use in the Ugi reaction, thereby yielding all six topologically possible combinations. The protocol is convergent and short and enables the production of novel disulfide peptidomimetics in a highly general fashion.

Cysteine Isocyanide in Multicomponent Reaction: Synthesis of Peptido-Mimetic 1,3-Azoles

An alternative approach toward the simple and robust synthesis of highly substituted peptidic thiazole derivatives using Ugi-multicomponent reaction (U-MCR) is described. Thus, we introduced the enantiopure (R)-2-methyl-2-isocyano-3-(tritylthio)propanoate as a novel class of isocyanide in MCR. This bifunctional isocyanide was found to undergo mild cyclodehydration to afford thiazole containing peptidomimetics in a short synthetic sequence. Several examples of bis-heterocyclic rings were also synthesized through the proper choice of the aldehyde component in the U-4CR. The method opens a wide range of applications toward the synthesis of nonribosomal natural products and other bioactive compounds.

Malonyl α-mercaptoketones and α-mercaptoalcohols, a new class of matrix metalloproteinase inhibitors

A novel series of matrix metalloproteinase (MMP) inhibitors is described. Incorporation of a terminal α-mercaptoketone or α- mercaptoalcohol in the zinc binding domain of a series of inhibitors led to compounds exhibiting low nanomolar activity against collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).

Heterocyclic inhibitors of farnesyl protein transferase

Inhibition of farnesyl protein transferase is effected by compounds of the formula its enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs or solvates thereof, wherein:, A1 and A2 are each independently H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, phenyl or substituted phenyl;, G1 is S or O;, G2 is H, -C(O)OH, -C(O)NH2, 5-tetrazolyl, -C(O)N(R7)OH or -CH2OH;, X is O or R8N;, Y and Z are each independently -CH2- or -C(O)-;, R1, R2, R3, R4, R5, R6 and R7 are each independently H or alkyl;, R1 may also be alkanoyl, R1 and A1 taken together may be -(CH2)m;, R8 is H, alkyl, phenyl, phenylalkyl, substituted phenyl, (substituted phenyl)alkyl or -C(O)R9;, R9 is H, alkyl, phenyl, phenylalkyl, substituted phenyl or (substituted phenyl)alkyl;, m is 3 or 4;, n is 0, 1 or 2;, p is 0, 1 or 2; and, q is 0 or 1, with the proviso that when p is 0, then q is also 0.