18323-56-3

Basic information

• Product Name: Z-ALA-LEU-NH2
• Synonyms: Z-ALA-LEU-NH2;CBZ-L-ALA-L-LEU NH2;Z-L-Ala-L-Leu-NH2;L-Leucinamide, N-[(phenylmethoxy)carbonyl]-L-alanyl-
• CAS NO: 18323-56-3
• Molecular Formula: C₁₇H₂₅N₃O₄
• Molecular Weight: 335.4
• Mol File: 18323-56-3.mol

Chemical Properties

• Boiling Point: 598.8°C at 760 mmHg
• Flash Point: 315.9°C
• Appearance: /
• Density: 1.152g/cm³
• Vapor Pressure: 2.67E-14mmHg at 25°C
• Refractive Index: 1.53
• Storage Temp.: -15°C
• CAS DataBase Reference: Z-ALA-LEU-NH2(CAS DataBase Reference)
• NIST Chemistry Reference: Z-ALA-LEU-NH2(18323-56-3)
• EPA Substance Registry System: Z-ALA-LEU-NH2(18323-56-3)

Safety Data

• Hazardous Substances Data: 18323-56-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C17H25N3O4/c1-11(2)9-14(15(18)21)20-16(22)12(3)19-17(23)24-10-13-7-5-4-6-8-13/h4-8,11-12,14H,9-10H2,1-3H3,(H2,18,21)(H,19,23)(H,20,22)

Upstream product

• 28819-05-8 (S)-2-benzyloxycarbonylamino-propionic acid methyl ester 
• 10466-61-2 (2S)-amino-4-methylpentanamide hydrochloride 
• 21844-68-8 N-benzyloxycarbonyl-L-alanine 4-picolyl ester 
• 67850-37-7 Z-L-Ala 2,2,2-trichloroethyl ester 
• 61543-49-5 Cbz-Ala Cs salt 
• 27167-66-4 Z-D-Ala-L-Leu-OMe 
• 203640-57-7 Z-D-Ala carbamoylmethyl ester 
• 687-51-4 H-L-Leu-NH₂ 
• 203640-41-9 Z-L-Ala 2,2,2-trifluoroethyl ester 
• 545390-96-3 Z-Ala-SMe 
• 1142-20-7 N-Cbz-Ala 
• 4816-87-9 Z-L-Ala carbamoylmethyl ester 
• 545391-03-5 2-benzyloxycarbonylamino-thiopropionic acid S-(4-guanidino-phenyl) ester 
• 203640-43-1 Z-L-Ala 4-cyanobenzyl ester 

Downstream Products

• 724733-56-6 Pyridine-2-carboxylic acid ((S)-1-{(1S,2S)-1-(4-bromo-benzyloxymethyl)-3-[(S)-1-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-ethylcarbamoyl]-2-hydroxy-propylcarbamoyl}-2-methyl-propyl)-amide 
• 724733-67-9 N-{(1S,2S)-1-(4-Bromo-benzyloxymethyl)-3-[(S)-1-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-ethylcarbamoyl]-2-hydroxy-propyl}-2,4,6-trifluoro-benzamide 
• 724733-53-3 (3S,4S)-4-azido-5-benzyloxy-3-hydroxypentanoic acid [(S)-1-((S)-1-carbamoyl-3-methylbutylcarbamoyl)ethyl]amide 
• 724733-52-2 (3S,4S)-4-azido-3-hydroxy-6-phenylhexanoic acid [(S)-1-((S)-1-carbamoyl-3-methylbutylcarbamoyl)ethyl]amide 

Relevant articles and documents

Mechanoenzymatic peptide and amide bond formation

Mechanochemical chemoenzymatic peptide and amide bond formation catalysed by papain was studied by ball milling. Despite the high-energy mixing experienced inside the ball mill, the biocatalyst proved stable and highly efficient to catalyse the formation of α,α- and α,β-dipeptides. This strategy was further extended to the enzymatic acylation of amines by milling, and to the mechanosynthesis of a derivative of the valuable dipeptide L-alanyl-l-glutamine.

Kinetically controlled peptide synthesis mediated by papain using the carbamoylmethyl ester as an acyl donor

A series of dipeptides were synthesized generally in good yields with carbamoylmethyl (Cam) esters as acyl donors in the presence of a cysteine protease, papain, immobilized on Celite. Several segment condensations were also achieved generally in high yields without danger of racemization and formation of the secondary-hydrolysis product. Moreover, partial sequences of some bioactive peptides were prepared through segment condensations, and aimed-at peptides were obtained generally in high yields without the racemization of C-terminal residues of the carboxyl components. Thus, the superiority of the Cam ester in the kinetically controlled peptide synthesis was once again ascertained in couplings mediated by the cysteine protease as in those catalyzed by the serine proteases reported earlier.

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.

Enzymatic synthesis of activated esters and their subsequent use in enzyme-based peptide synthesis

Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides. However, there are still some limitations when challenging peptides, e.g. containing sterically demanding acyl donors, non-proteinogenic amino acids or proline residues, are to be synthesized. To remedy these limitations, special ester moieties have been used that are specifically recognized by the enzyme, e.g. guanidinophenyl, carboxamidomethyl (Cam) or trifluoroethyl (Tfe) esters, which, unfortunately, are notoriously difficult to synthesize chemically. Herein, we demonstrate that Cam and Tfe esters are very useful for Alcalase-CLEA mediated peptide synthesis using sterically demanding and non-proteinogenic acyl donors as well as poor nucleophiles, and combinations thereof. Furthermore, these esters can be efficiently synthesized by using the lipase Cal-B or Alcalase-CLEA. Finally, it is shown that the ester synthesis by Cal-B and subsequent peptide synthesis by Alcalase-CLEA can be performed simultaneously using a two-enzyme-one-pot approach with glycolamide or 2,2,2-trifluoroethanol as additive.

α-Chymotrypsin-catalyzed peptide synthesis in frozen aqueous solution using N-protected amino acid carbamoylmethyl esters as acyl donors

A kinetically controlled peptide synthesis catalyzed by α-chymotrypsin was performed in frozen aqueous solution (ice, -24 °C). The yield of the peptide was significantly improved by the use of the carbamoylmethyl (Cam) ester as the acyl donor instead of the conventional ethyl ester. The peptide yield increased up to ca. 90% when N-benzyloxycarbonyl (CBZ)-Phe-OCam and H-Phe-NH2 were used as the acyl donor and nucleophile, respectively. Such an improvement of the peptide yield in ice was also observed in the coupling of other CBZ-amino acid Cam esters as acyl donors. Furthermore, this approach was applied to the synthesis of peptides containing d-amino acids. The peptides such as CBZ-d-Phe-Phe-NH2, CBZ-Phe-d-Phe-NH2 and CBZ-d-Phe-d-Phe-NH2 were also obtained in excellent to moderate yields in ice. A high diastereoselectivity towards the l-l peptide was observed when the racemic amino acid Cam ester was used as the acyl donor in ice.

Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II. Use of solid-phase synthesis to explore novel statine motifs

Picomolar to low nanomolar inhibitors of the two aspartic proteases plasmepsin (Plm) I and II, from the malaria parasite Plasmodium falciparum, have been identified from sets of libraries containing novel statine-like templates modified at the amino and c

Reverse proteolysis promoted by in situ generated peptide ester fragments

In this contribution we describe a general synthesis concept for the in situ preparation of protease specific reactants using methyl thioesters as universal precursors. The precursor esters are readily available by standard synthesis procedures and can be

Superiority of the carbamoylmethyl ester as an acyl donor for the kinetically controlled amide-bond formation mediated by α-chymotrypsin

The superiority of the carbamoylmethyl ester as an acyl donor for the α-chymotrypsin-catalysed kinetically controlled peptide-bond formation is demonstrated in the couplings of an inherently poor amino acid substrate, Ala, with various amino acid residues as amino components and in the couplings of non-protein amino acids such as halogenophenylalanines as carboxylic components. Furthermore, this approach is applied to the amide-bond formation between an amino acid residue and a chiral amine, which is highly diastereoselective.

Broadening of the substrate tolerance of α-chymotrypsin by using the carbamoylmethyl ester as an acyl donor in kinetically controlled peptide synthesis

In the kinetically controlled approach of peptide synthesis mediated by α-chymotrypsin, the broadening of the protease's substrate tolerance is achieved by switching the acyl donor from the conventional methyl ester to the carbamoylmethyl ester. Thus, as a typical example, the extremely low coupling efficiency obtained by employing the methyl ester of an inherently poor amino acid substrate, Ala, is significantly improved by the use of this particular ester. Its ameliorating effect is observed also in the couplings of other amino acid residues such as Gly and Ser as carboxy components.

Remarkable effects of donor esters on the α-chymotrypsin-catalyzed couplings of inherently poor amino acid substrates

The extremely low efficiency during the α-chymotrypsin-catalyzed coupling of an inherently poor amino acid substrate, e.g., alanine, using the methyl ester as an acyl donor was significantly improved using esters such as the 2,2,2-trifluoroethyl or carbamoylmethyl ester. The ameliorating effect of the latter ester was especially significant.