6491-60-7

Upstream product

• 6940-46-1 N-(α-bromo-isovaleryl)-glycine 
• 74088-26-9 N-(N-benzyloxycarbonyl-DL-valyl)-glycine 
• 40331-73-5 4-isopropyl-3-(2-nitro-phenylsulfanyl)-oxazolidine-2,5-dione 
• 56-40-6 glycine 
• 85864-65-9 [(S)-2-(2-{(S)-2-[2-((S)-2-Amino-3-phenyl-propionylamino)-acetylamino]-4-methyl-pentanoylamino}-acetylamino)-3-methyl-butyrylamino]-acetic acid 
• 7664-41-7 ammonia 
• 10323-40-7 2-bromoisovaleric acid 
• 27109-47-3 2-bromoisovaleryl chloride 
• 1149-26-4 N-benzyloxycarbonylvaline 
• 7801-65-2 N-(N-benzyloxycarbonyl-DL-valyl)-glycine ethyl ester 
• 516-06-3 D,L-valine 
• 2816-12-8 4-isopropyl-2,5-oxazolidinedione 
• 3479-71-8 Boc-D-Val-Gly-OEt 
• 1803-57-2 N-[N-formyl-L-valyl=>glycine 

Downstream Products

• 16944-60-8 3-isopropyl-piperazine-2,5-dione 
• 95753-63-2 DL-5-isopropyl-3-<4-<(2S)-Fmocamino-2-methoxycarbonylethyl>phenyl>-2-thiohydantoin 
• 69288-25-1 alanyl=>valyl=>glycine 

Relevant academic research and scientific papers

N-carbamoyl derivatives and their nitrosation by gaseous NOx - A new, promising tool in stepwise peptide synthesis

New uses of the N-carbamoyl group in peptide synthesis as an Nα-protecting group in classical peptide coupling methods, and as a preactivating group for stepwise coupling by NCA formation - are presented. In the first application, the N-carbamoyldipeptide esters C-Val-Gly-OEt, C-Leu-Gly-OEt, C-Ala-Gly-OEt, and C-Ala-Phe-OEt were obtained in good yields by treatment of the corresponding N-carbamoylamino acids (CAA) with amino acid esters. Quantitative N-deprotection without racemisation was then achieved in the solid through nitrosation by gaseous NOx. The extent of racemisation occurring in the coupling step is discussed. In the second application, an easy route to amino acid N-carboxy anhydrides (NCAs) through nitrosation of CAA under the same conditions as above allowed straightforward "one-pot" peptide stepwise coupling, as demonstrated by the formation of Leu-Gly and Val-Gly in good yields and enantiomeric excess. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Structure-CaSR-activity relation of kokumi γ-glutamyl peptides

Modulation of the calcium sensing receptor (CaSR) is one of the physiological activities of γ-glutamyl peptides such as glutathione (γ-glutamylcysteinylglycine). γ-Glutamyl peptides also possess a flavoring effect, i.e., sensory activity of kokumi substances, which modifies the five basic tastes when added to food. These activities have been shown to be positively correlated, suggesting that kokumi γ-glutamyl peptides are perceived through CaSRs in humans. Our research is based on the hypothesis that the discovery of highly active CaSR agonist peptides will lead to the creation of practical kokumi peptides. Through continuous study of the structure-CaSR-activity relation of a large number of γ-glutamyl peptides, we have determined that the structural requirements for intense CaSR activity of γ-glutamyl peptides are as follows: existence of an N-terminal γ-L-glutamyl residue; existence of a moderately sized, aliphatic, neutral substituent at the second residue in an L-configuration; and existence of a C-terminal carboxylic acid, preferably with the existence of glycine as the third constituent. By the sensory analysis of γ-glutamyl peptides selected by screening using the CaSR activity assay, γ-glutamylvalylglycine was found to be a potent kokumi peptide. Furthermore, norvaline-containing γ-glutamyl peptides, i.e., γ-glutamylnorvalylglycine and γ-glutamylnorvaline, possessed excellent sensory activity of kokumi substances. A novel, practical industrial synthesis of regiospecific γ-glutamyl peptides is also required for their commercialization, which was achieved through the ring opening reaction of N-α-carbobenzoxy-L-glutamic anhydride and amino acids or peptides in the presence of N-hydroxysuccinimide.

Coupling-Reagent-Free Synthesis of Dipeptides and Tripeptides Using Amino Acid Ionic Liquids

A general method for the synthesis of dipeptides has been developed, which does not require any coupling reagents. This method is based on the reaction of readily available HCl salts of amino acid methyl esters with tetrabutylphosphonium amino acid ionic liquids. The isolation procedure of stepwise treatment with AcOH is easy to carry out. The method was extended to the synthesis of tripeptide, tyrosyl-glycyl-glycine, present in IMREG-1, also.

METHOD FOR PRODUCING GAMMA -GLUTAMYL-VALYL-GLYCINE CRYSTAL

The present invention provides a method for efficiently producing a γ-glutamyl-valyl-glycine crystal. Specifically, the present invention provides a method for producing a γ-glutamyl-valyl-glycine crystal, which includes the steps of: preparing a mixed solution of valyl-glycine or a salt thereof and γ-glutamyl-valyl-glycine, wherein the mixed solution contains valyl-glycine or the salt thereof in an amount of 20 mass % or more relative to the mass of γ-glutamyl-valyl-glycine; adjusting the amount of valyl-glycine or the salt thereof in the prepared mixed solution to 0.1 mass % or more and less than 20 mass % relative to the mass of γ-glutamyl-valyl-glycine to prepare a γ-glutamyl-valyl-glycine solution; and subjecting the γ-glutamyl-valyl-glycine solution to a crystallization procedure to produce the γ-glutamyl-valyl-glycine crystal.

N -boc deprotection and isolation method for water-soluble zwitterionic compounds

A highly efficient TMSI-mediated deprotection and direct isolation method to obtain zwitterionic compounds from the corresponding N-Boc derivatives has been developed. This method has been demonstrated in the final deprotection/isolation of the β-lactamase inhibitor MK-7655 as a part of its manufacturing process. Further application of this process toward other zwitterionic compounds, such as dipeptides and tripeptides, has been successfully developed. Furthermore, a catalytic version of this transformation has been demonstrated in the presence of BSA or BSTFA.

Stereoselective ring contraction of 2,5-diketopiperazines: An innovative approach to the synthesis of promising bioactive 5-membered scaffolds

Ring contraction of 2,5-diketopiperazines by TRAL-alkylation led us to the stereoselective synthesis of original pyrrolidine-2,4-diones, a novel series of promising molecules with moderate anti-proliferative activity on breast cancer cells.

Rates of reduction of N-chlorinated peptides by sulfite: Relevance to incomplete dechlorination of wastewaters

Biologically induced fragmentation of proteins during wastewater treatment produces peptides, which form long-lasting organic chloramines when the water is disinfected with Cl2. To protect aquatic wildlife from residual chlorine, including chloramines, wastewaters are often treated with sulfur dioxide or sulfite salts. This strategy incompletely eliminates residual chlorine species. Here we report that dechlorination rate constants of N- chloropeptides are 1-2 orders of magnitude smaller than those for NH2Cl and some aliphatic organic chloramines. Slow rates explain the prevalence of N- chloropeptides in dechlorinated wastewaters after faster reacting chlorine species have been eliminated. Dechlorination is subject to general acid catalysis. For N-chlorinated leucylalanine, the rate law above pH 6 in phosphate buffer at 25 °C and / ? 0.1 M is as follows: rate = (9.92 ± 0.41 x 103[H2PO4-] + 5.70 ± 0.52 x 108[H3O+] + 5.3 ± 0.2)[SO32-][Cl- Leu-Ala] (concentrations in M, time in s). Rate constants for other peptides appear to be of similar magnitude; variations in the acid-catalyzed terms among different hydrophobic peptides correlate with solvation energies of side chains. The kinetic data suggest that reducing N-chloropeptides in wastewaters by 75% or more will require reaction times generally >0.5 h at environmentally acceptable S(IV) doses and pH values. Biologically induced fragmentation of proteins during wastewater treatment produces peptides, which form long-lasting organic chloramines when the water is disinfected with Cl2. To protect aquatic wildlife from residual chlorine, including chloramines, wastewaters are often treated with sulfur dioxide or sulfite salts. This strategy incompletely eliminates residual chlorine species. Here we report that dechlorination rate constants of N-chloropeptides are 1-2 orders of magnitude smaller than those for NH2Cl and some aliphatic organic chloramines. Slow rates explain the prevalence of N-chloropeptides in dechlorinated wastewaters after faster reacting chlorine species have been eliminated. Dechlorination is subject to general acid catalysis. For N-chlorinated leucylalanine, the rate law above pH 6 in phosphate buffer at 25 °C and I≈0.1 M is as follows: rate = (9.92±0.41×103[H2 PO4- ]+5.70±0.52×108[ H3O+]+5.3±0.2) [SO32-][Cl-Leu-Ala] (concentrations in M, time in s). Rate constants for other peptides appear to be of similar magnitude; variations in the acid-catalyzed terms among different hydrophobic peptides correlate with solvation energies of side chains. The kinetic data suggest that reducing N-chloropeptides in wastewaters by 75% or more will require reaction times generally >0.5 h at environmentally acceptable SIV doses and pH values.

Practical synthesis of Schollkopf's bis-lactim ether chiral auxiliary: (3S)-3,6-dihydro-2,5-dimethoxy-3-isopropyl-pyrazine

Practical methodology for the bis-O-methylation of (3S)-isopropyl-piperazine-2,5-dione 4 on a 45 g scale to generate Schollkopf's bis-lactim ether chiral auxiliary (3S)-3,6-dihydro-2,5-dimethoxy-3-isopropyl-pyrazine 1 has been developed. Monomethylated intermediates 5 and 6 are reported for the first time. The gelling effects of 4 in a range of common solvents are also described.

Direct Cleavage versus Transpeptidation in the Autodecomposition of Peptides Containing 2,4-Diaminobutanoic Acid (DABA) and 2,3-Diaminopropanoic Acid (DAPA) Residues. Specific Cleavage of DAPA-Containing Peptides

Peptides containing 2,4-diaminobutanoic acid and 2,3-diaminopropanoic acid residues undergo transpeptidation by attack of their side-chain amino groups on the N-carbonyl (eq. 2).Little or no direct cleavage by attack on the C-carbonyl (eq. 1) is observed.The transpeptidation reactions of peptides containing 2,4-diaminobutanoic acid (DABA) or 2,3-diaminopropanoic acid (DAPA) residues reach an equilibrium in which the various peptides studied are about 70-80percent transpeptidized; this extent of transpeptidation is in aggreement with the equilibrium constants for othertransamination reactions.The transpeptidation reaction is strongly catalyzed by phosphate and bicarbonate buffers, and the pH dependence of the reaction suggests that an unprotonated side-chain amino group is required for significant reactivity.The rate of the transpeptidation reaction is retarded by bulky substituents at the α-carbon of the residue at the amino-terminal side of the DAPA or DABA residue.The preference for transpeptidationdirect cleavage in the case of DABA residues can be explained by one or more of the following factors: (1) a preference for (Z)-amide (transpeptidation)(E)-amide (direct cleavage); (2) greater ring strain in the tetrahedral intermediate for direct cleavage; (3) a steric effect resulting from unfavorable interactions in the possible transition states for direct cleavage (Scheme III).A stereoelectronic explanation is considered and rejected.Peptides containing transpeptidized DABA and DAPA residues (isoDABA and isoDAPA residues, respectively) undergo cleavage at the carboxy-terminal side of these residues on treatment with the Edman reagent followed by treatment with trifluoroaceticacid.Peptides can be induced to undergo direct cleavage at the carboxy-terminal side of untranspeptidized DAPA residues by treatment with the Edman reagent followed by heptafluorobutyric acid.The chemical and biological significance of these observations is discussed.

Peptide Decomposition in the Neutral pH Region via the Formation of Diketopiperazines

In the neutral pH region, the decomposition of the tripeptides Leu-Gly-Gly and Gly-Leu-Gly at 130 deg C and the hexapeptide Phe-Gly-Leu-Gly-Val-Gly at 100 deg C has been found to involve the formation of diketopiperazines from the N-terminal position of the peptides.