76491-40-2

Upstream product

• 67436-17-3 dimethyl (S)-N-(benzyloxycarbonyl)glutamate 
• 208453-16-1 (S)-4-Benzyloxycarbonylamino-4-ethylsulfanylcarbonyl-butyric acid methyl ester 
• 2650-64-8 Cbz-L-Gln 
• 1155-62-0 N-benzyloxycarbonyl-L-glutamic acid 
• 32668-18-1 Z-Gln-Ser-OMe 
• 6525-53-7 L-glutamic acid dimethyl ester 
• 13139-52-1 N-carbobenzoxy-D-glutamine 
• 67436-17-3 benzyloxycarbonylglutamic acid dimethyl ester 
• 4124-76-9 N-(benzyloxycarbonyl)-L-glutamic acid anhydride 
• 821788-04-9 Carbobenzoxy-L-glutaminsaeure-1-thioethylester 
• 501-53-1 benzyl chloroformate 
• 63648-73-7 N-benzyloxycarbonyl-D-glutamic acid 

Downstream Products

• 86095-99-0 (S)-2-Amino-pentanedioic acid diamide; compound with toluene-4-sulfonic acid 
• 63092-13-7 1-O-benzyl-4,6-O-benzylidene-N-acetylmuramyl-alanyl-D-glutamic acid diamide 
• 76491-41-3 benzyloxycarbonylalanyl-D-glutamic acid diamide 

Relevant academic research and scientific papers

Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine

Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.

Convenient preparation of primary amides via activation of carboxylic acids with ethyl chloroformate and triethylamine under mild conditions

Primary amides were easily prepared in 22-99% yields from the corresponding carboxylic acids 1 or 5 with NH4Cl via activation with ClCO 2Et and Et3N. The enantiomers of the corresponding primary amides of Cbz-, Boc-, or Fmoc-α-amino acids can be separated by using a chiral column.

Enzymatic C-terminal amidation of amino acids and peptides

Herein, we describe two versatile and high yielding enzymatic approaches for the conversion of semi-protected amino acid and peptidyl C-terminal α-carboxylic acids into their corresponding amides. In the first approach, the lipase Candida antarctica lipase-B (Cal-B), and in the second approach, the protease Subtilisin A, are used, respectively. We found that by using the ammonium salt of the α-carboxylic acid instead of separate ammonia sources, the enzymatic amidation reactions proceeded much faster without side reactions and gave near to quantitative yields of products.

Protein backbone modification by novel C(α)-C side-chain scission

α-Ketoamide (-NH-CO-CO-) units in intact peptides are generated from Ser/Thr residues via Ru(VIII)-catalyzed C(α)-C side-chain scission. Facets associated with this novel α-carbon modification have been probed with 75 peptides chosen to represent every possible peptide environment. The reactions were carried out at room temperature with in situ generated Ru(VIII) in biphasic (CH3CN/CCl4/pH 3 phosphate buffer, 1:1:2 v/v) medium. Whereas Ser/Thr residues placed at the C-terminal end in peptides undergo N-C bond scission leading to des-Ser/Thr peptide amides - thus acting as Gly equivalents in simulating the α-amidating action of pituitary enzymes - those located at the N-terminal or nonterminal or even at the C-terminal position (protected as amide) were found to undergo oxidative C-C bond scission (involving C(α) and C side-chain bond), resulting in the generation of α-ketoamide (-NH-CO-CO-) units in the intact peptide backbone. The difference in the products arising from C(α)-C side-chain scission of Ser/Thr esters and amides is rationalized on the basis of a common mechanism involving either oxaloesters [PeP-NH-CO-COX; X = OMe] or oxalamides [X = NH2 or NH-Pep] arising from the oxidation of initially formed carbinolamide intermediates [Pep-NH-CH(OH)-COX], wherein, while the former are shown to undergo hydrolysis to terminal amides [Pep-NH2], the oxalamides are found to be stable to hydrolysis. Ancillary noteworthy findings are those of peptide bond scission when contiguous Ser-Ser/Thr-Thr residues are present and the oxidative cleavage at C-terminal Tyr/Trp sites generating des amides. The oxidative methodology presented here is mild, simple, and practical and proceeds with chiral retention. The insensitivity of a large number of amino acid residues, such as Gly, Ala, Leu, Asn, Gln, Asp, Glu, Pro, Arg, Phe, Lys, Val, and Aib, and N-protecting groups, such as Boc, Z, and Bz, toward Ru(VIII) under the experimental conditions should make this methodology practical and useful. Sulfur-containing amino acids Cys and Met get oxidized to sulfones in the products.

'BOP' as a reagent for mild and efficient preparation of esters

A simple procedure for preparation of esters under mild conditions employing the BOP reagent is reported. Acid and base labile protecting groups commonly used with amino acids e.g. t-butyl, Fmoc etc., are well tolerated under these conditions. The mechani

SYNTHESIS OF PEPTIDES, GLYCO DERIVATIVES AND GLYCOPEPTIDES FROM BACTERIAL CELL WALLS

Synthesis in solution and in solid phase was used to prepare alanyl-D-isoglutamine (VI), alanyl-D-isoglutaminyl-Nε-p-toluenesulfonyl-lysyl-D-alanine methyl ester (XIII), alanyl-D-isoglutaminyl-Nε-acetyl-lysyl-D-alanine methyl ester (XIV), alanyl-D-isoglutaminyl-Nε-acetyl-lysyl-D-alanyl-pentaglycine methyl ester and amide (XXXI, XXXII), methyl ester (XXXV), methyl ester (XXXVII), N-acetylmuramyl-alanyl-D-isoglutaminyl-Nε-acetyl-lysyl-D-alanyl-pentaglycine amide (XXXIX), methyl ester (XLI), and methyl ester (XLIII).Thetetrapeptides, nonapeptides, and tridecapeptides show a pronounced pyrogenic effect.Imunoadjuvant activity was observed not only with the glycopeptides but also with nonapeptide XXXI.