28862-79-5

Basic information

• Product Name: N-Cbz-D-Leucine
• Synonyms: N-CBZ-D-LEUCINE;N-ALPHA-BENZYLOXYCARBONYL-D-LEUCINE;N-ALPHA-CARBOBENZOXY-D-LEUCINE;N-CARBOBENZOXY-D-LEUCINE;N-BENZYLOXYCARBONYL-D-LEUCINE;N-ALPHA-CBZ-D-LEUCINE;Z-D-LEUCINE;Z-D-LEU-OH
• CAS NO: 28862-79-5
• Molecular Formula: C₁₄H₁₉NO₄
• Molecular Weight: 265.3
• EINECS: 1533716-785-6
• Mol File: 28862-79-5.mol

Chemical Properties

• Boiling Point: 442.8 °C at 760 mmHg
• Flash Point: 221.6 °C
• Appearance: clear colorless - yellow oil
• Density: 1.158 g/cm³
• Storage Temp.: 2-8°C
• PKA: 4.00±0.21(Predicted)
• BRN: 2057659
• CAS DataBase Reference: N-Cbz-D-Leucine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Cbz-D-Leucine(28862-79-5)
• EPA Substance Registry System: N-Cbz-D-Leucine(28862-79-5)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 28862-79-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N-Cbz-D-Leucine is used as a reactant for the synthesis of MG-132, a tripeptide aldehyde proteasome inhibitor. N-Cbz-D-Leucine plays a crucial role in the development of drugs targeting the ubiquitin-proteasome pathway, which is involved in various cellular processes, including protein degradation and cell cycle regulation. By inhibiting the proteasome, MG-132 can be employed in the treatment of various diseases, such as cancer and neurodegenerative disorders, where the dysregulation of protein degradation is a significant factor.

Upstream product

• 19506-72-0 benzyl-8-quinolyl carbonate 
• 328-39-2 LEUCINE 
• 91806-74-5 3,5-dimethyl-pyrazole-1-carboxylic acid benzyl ester 
• 501-53-1 benzyl chloroformate 
• 687-51-4 H-L-Leu-NH₂ 
• 100-51-6 benzyl alcohol 
• 2018-66-8 N-carbobenzyloxy leucine 
• 62-53-3 aniline 
• 52235-17-3 2(R)-(carbobenzoxy)amino-4-methylpentanoic acid p-nitrophenyl ester 
• 6216-61-1 (S)-(-)-N-(benzyloxycarbonyl)leucinol 
• 70853-26-8 (R)-4-methyl-1-oxopentane-2-benzylcarbamate 
• 174657-99-9 (R)-2-Benzyloxycarbonylamino-4-methyl-pentanoic acid 4-nitro-benzyl ester 
• 920-36-5 (2-methylpropyl)lithium 
• 193091-62-2 (E)-(R)-O-(1-phenylbutyl)cinnamaldehyde oxime 

Downstream Products

• 4108-19-4 D(L)-Z-Leu-PNP 
• 122272-76-8 (N-benzyloxycarbonyl-leucyl)-phosphoric acid dibenzyl ester 
• 111411-33-7 N-benzyloxycarbonyl-DL-thioleucine S-(4-nitro-phenyl ester) 
• 3190-70-3 4-(2-methylpropyl)oxazolidine-2,5-dione 
• 55387-20-7 N-(N-benzyloxycarbonyl-DL-leucyl)-N'-isonicotinoyl-hydrazine 
• 4821-82-3 N-benzyloxycarbonyl-DL-leucine cyanomethyl ester 
• 102156-97-8 N-benzyloxycarbonyl-DL-thioleucine S-phenyl ester 
• 21931-02-2 (S)-benzyl 4-methyl-1-oxo-1-(phenylamino)pentan-2-ylcarbamate 
• 2778-33-8 N-(N-benzyloxycarbonyl-DL-leucyl)-glycine ethyl ester 
• 76444-99-0 leucine cyclohexyl ester 
• 18869-43-7 DL-leucine methyl ester 
• 38689-31-5 _(D)Leu-_(L)Leu 
• 7664-02-0 4-(N-Benzyloxycarbonyl-DL-leucylamino)-6-methyl-heptanon-⁽³⁾-semicarbazon 
• 93997-21-8 DL-N-Carbobenzoxy-leucin-bis-(2-chloraethyl)-amid 

Relevant articles and documents

Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors

Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.

Enantioselective inclusion of pyrene-1-sulfonate salts of α-amino acids with crystals of α-cyclodextrin

Enantioselective inclusion of α-amino acids with crystals of α-cyclodextrin (α-CD) has been achieved by converting the amino acids into sulfonate salts with pyrene-1-sulfonic acid (PyS). For example, crystals of α-CD selectively include L-leucine/PyS (1:1) salt in a host/guest ratio of ～1 with 92%ee from a solution of the racemic salt in ethanol/N-methylformamide (91:9) at 40 °C. Under conditions optimized for individual amino acids, the PyS salts of valine, phenylalanine, and methionine are also included with good enantioselectivities (up to 86%ee). Mechanistic studies for the inclusion of leucine/PyS salt reveals that the enantioselectivity originates from the difference in stability between the inclusion complexes of D- and L-leucine/PyS salts with α-CD in crystals.

Chiral tetraaryl-and tetraalkynylborates as chiral solvating agents for tetraalkylammonium salts

The application of tetracarbon-substituted chiral borate sodium salts (NaBR*4) as NMR chiral solvating agents for various tetraalkylammonium salts (R4NX) has been successfully demonstrated. Ion exchange between R4NX and NaBR*4 proceeded in excellent yields and provided the corresponding dia-stereomeric salts (R4NBR*4). The ee values of the R4NX salts were determined by1H NMR analysis of R4NBR*4. Two types of chiral borates, tetraaryl-and tetraalkynylborates with optically active 1,1′-binaphthyl components were used. At the beginning of this research, we investigated the efficacy of a known chiral tetraar-ylborate developed by Pommerening et al. for R4NX. To expand the possibility of further structural design of the chiral borate, we designed chiral tetraalkynylborates as a new structure. Their synthesis and application are also described.

Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches

Here we report a series of potent anti-HCV agents bearing a symmetrical benzidine l-prolinamide backbone with different capping groups including alkyl/aryl carbamates of natural and unnatural valine and leucine amino acids. All compounds were investigated for their inhibitory activity in an HCV replicon assay on genotype 1b. The novel compounds share some chemical and clinical attributes of commercially available NS5A inhibitors. Compounds 5 and 6 with unnatural capping residue and ethyl and isobutyl carbamates showed EC50 values in the picomolar range with a low toxicity profile and selectivity indices of several orders of magnitude. These findings enlarge the chemical space from which NS5A inhibitors may be discovered by adopting unnatural amino acids, amino acids other than valine and carbamates other than methyl as the capping groups.

Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy

A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.

Synthesis, screening and docking of small heterocycles as Glycogen Phosphorylase inhibitors

A series of morpholine substituted amino acids (phenylalanine, leucine, lysine and glutamic acid) was synthesized. A fragment-based screening approach was then used to evaluate a series of small heterocycles, including morpholine, oxazoline, dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3-pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H-benzimidazole, as potential inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved potency (IC50 of 25 μM) and had good LE and LELP values, as compared to heterocycles 1, 5, 9e13 and 19 (IC50 values of 1.1 mM e23.9 mM). A docking study using the crystal structure of human liver Glycogen Phosphorylase, provided insight into the interactions of heterocycles 5, 7, 9e13 and 19 with Glycogen Phosphorylase.

Synthesis of enantiopure free and N-benzyloxycarbonyl-protected 3-substituted homotaurines from naturally occurring amino acids

Enantiopure N-benzyloxycarbonyl-protected and free 3-substituted homotaurines were synthesized from naturally occurring amino acids via N-benzyloxycarbonyl protection, Arndt-Eistert homologation, reduction, esterification with thioacetic acid, and oxidation with performic acid. The current method is a convenient, practical, and salt-free method for the synthesis of enantiopure 3-substituted homotaurine with moderate to good yields.

A Stereoselective entry into functionalized 1,2-diamines by zinc-mediated homologation of α-aminoacids

A general, stereoselective synthsis of 4,5-disubstituted imidazolidines-2-ones from α-aminoacids has been developed: the key steps are a Biaise reaction of bromoacetate on α-aminonitriles and further reduction. Although reduction with sodium cyanoborohydride afforded a mixture of cis and trans isomers 6a-e with moderate to good stereoselectivity, reduction with sodium in liquid ammonia gave the trans isomers 8a-e with complete stereoselectivity. Acidic hydrolysis of the urea gave 4-amino-pyrrolidinones, which can be precursors to β,γ-diaminoacids or 3-aminopyrrolidines.

Scope and limitations of sodium and potassium trimethylsilanolate as reagents for conversion of esters to carboxylic acids

Sodium or potassium trimethylsilanolate act as versatile and very powerful reagents for conversion of a wide variety of esters to carboxylic acids. The reactions were performed in tetrahydrofuran under mild reaction conditions with high to quantitative yields.

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.