111771-58-5

Basic information

• Product Name: BOC-ALPHA-METHYL-L-PHE
• Synonyms: BOC-(S)-2-AMINO-2-METHYL-3-PHENYLPROPANOIC ACID;BOC-ALPHA-METHYL-L-PHE;BOC-ALPHA-METHYL-L-PHENYLALANINE;BOC-ALPHA-BENZYL-L-ALA;N-BOC-ALPHA-METHYL-L-PHENYLALANINE;N-BOC-A-METHYL-L-PHENYLALANINE;Boc-alphaMe-L-Phe-OH;Boc-α-methyl-L-phenylalanine
• CAS NO: 111771-58-5
• Molecular Formula: C₁₅H₂₁NO₄
• Molecular Weight: 279.33
• Product Categories: Unusual amino acids;unnatural amino acids
• Mol File: 111771-58-5.mol

Chemical Properties

• Boiling Point: 432.1±38.0 °C(Predicted)
• Appearance: /
• Density: 1.140±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 3.92±0.11(Predicted)
• CAS DataBase Reference: BOC-ALPHA-METHYL-L-PHE(CAS DataBase Reference)
• NIST Chemistry Reference: BOC-ALPHA-METHYL-L-PHE(111771-58-5)
• EPA Substance Registry System: BOC-ALPHA-METHYL-L-PHE(111771-58-5)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 111771-58-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
BOC-ALPHA-METHYL-L-PHE is used as a reagent in the discovery of oxadiazoyl tertiary carbinamine inhibitors of β-secretase (BACE-1). It plays a crucial role in the development of potential therapeutic agents targeting Alzheimer's disease by inhibiting the enzyme responsible for amyloid-beta peptide production.
Used in Medicinal Chemistry:
BOC-ALPHA-METHYL-L-PHE is utilized in the study of strategies aimed at improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors. This research is vital for enhancing the effectiveness of drugs designed to cross the blood-brain barrier and treat neurological disorders, such as Alzheimer's disease.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 23239-35-2 (S)-2-amino-2-methyl-3-phenylpropanoic acid 
• 1443008-10-3 (S)-2-amino-N-((1S,2S)-2-hydroxy-1,2-diphenylethyl)-N,2-dimethyl-3-phenylpropanamide 
• 1132-26-9 2-methyl-3-phenylalanine 
• 64384-47-0 2-amino-3-phenyl-2-methylpropanenitrile 
• 103-79-7 1-phenyl-acetone 
• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 
• 1393737-29-5 (S)-4-benzyl-3-tert-butoxycarbonyl-4-methyl-2-oxazolidinone 
• 1393737-59-1 (S)-4-benzyl-4-methyl-2-oxazolidinone 
• 1393737-50-2 (S)-(4-benzyl-2-oxazolidinon-4-yl)methyl p-toluenesulfonate 
• 1393737-23-9 diethyl 2-benzyl-2-(N-((S)-α-methylbenzyl)amino)malonate hydrochloride 
• 1393737-47-7 (R)-4-benzyl-4-hydroxymethyl-2-oxazolidinone 
• 1393737-40-0 (4R,αS)-4-benzyl-4-hydroxymethyl-3-(α-methylbenzyl)-2-oxazolidinone 

Downstream Products

• 1428736-37-1 (2S)-2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropanamide 
• 1428736-40-6 (2R,5S)-5-benzyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one 
• 1428736-42-8 (2S,5S)-5-benzyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one 
• 1428736-44-0 (2R,5S)-5-benzyl-2,5-dimethyl-2-(pyridine-2-yl)imidazolidine-4-one 
• 1428736-46-2 (2S,5S)-5-Benzyl-2,5-dimethyl-2-(pyridine-2-yl)imidazolidine-4-one 
• 361521-83-7 [(R)-2-(tert-butoxycarbonylamino)-2-methyl-3-phenylpropanoyl]-L-alanine benzyl ester 
• 928330-65-8 2-tert-butoxycarbonylamino-2-methyl-3-phenyl-propionic acid 3-[1-(4-fluoro-phenyl)-ethylcarbamoyl]-5-(methanesulfonyl-methyl-amino)-benzyl ester 
• 868286-83-3 (1-{5-[3-[1-(4-fluoro-phenyl)-ethylcarbamoyl]-5-(methanesulfonyl-methyl-amino)-phenyl]-[1,3,4]oxadiazol-2-yl}-1-methyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 851306-99-5 ((R)-1-methyl-1-methylcarbamoyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 868286-30-0 R-N-(tert-butoxycarbonyl)-α-methylphenylalaninamide 
• 925455-53-4 tert-butyl (1R)-1-benzyl-2-{2-[(7-ethyl-1-methyl-2,2-dioxido-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indol-9-yl)carbonyl]hydrazino}-1-methyl-2-oxoethylcarbamate 
• 182509-10-0 Boc-(D)-α-methylcyclohexylalanine 
• 118111-41-4 (R)-N-<(1,1-dimethylethyl)oxycarbonyl>-2-methyl-3-phenylalanyl-(2S,3R)-<2,3-2H2>-2-amino-4-butyrolactone 
• 118203-62-6 (R)-N-<(1,1-dimethylethyl)oxycarbonyl>-2-methyl-3-phenylalanyl-(2R,3S)-<2,3-2H2>-2-amino-4-butyrolactone 

Relevant articles and documents

Diastereoselective Alkylation of Sultam-Derived Amino Acid Aldimines Preparation of Cα-Methylated Amino Acids

Alkylation of Schiff bases 2 derived from 4-chlorobenzaldehyde and sultam-derived amino acids 1 gave crystalline diastereomers 3 which after deprotection and re-crystallization, if necessary, afforded in good yield enantiomerically pure Cα-methylated amin

METHOD FOR SYNTHESIZING OPTICALLY ACTIVE a-AMINO ACID USING CHIRAL METAL COMPLEX COMPRISING AXIALLY CHIRAL N-(2-ACYLARYL)-2-[5,7-DIHYDRO-6H-DIBENZO[c,e]AZEPIN-6-YL] ACETAMIDE COMPOUND AND AMINO ACID

Objects of the present invention are to provide an industrially applicable method for producing an optically active α-amino acid in high yield and in a highly enantioselective manner, to provide a simple production method of an optically active α,α-disubstituted α-amino acid, and to provide an intermediate useful for the above production methods of an optically active α-amino acid and an optically active α,α-disubstituted α-amino acid. The present invention provides a production method of an optically active α-amino acid or a salt thereof, the production method comprising introducing a substituent into the α carbon in the α-amino acid moiety of a metal complex represented by the following Formula (1): by an alkylation reaction, an aldol reaction, the Michael reaction, or the Mannich reaction, and releasing an optically pure α-amino acid enantiomer or a salt thereof by acid decomposition of the metal complex.

METHOD FOR SYNTHESIZING OPTICALLY ACTIVE α-AMINO ACID USING CHIRAL METAL COMPLEX COMPRISING AXIALLY CHIRAL N-(2-ACYLARYL)-2-[5,7-DIHYDRO-6H-DIBENZO[c,e]AZEPIN-6-YL]ACETAMIDE COMPOUND AND AMINO ACID

Objects of the present invention are to provide an industrially applicable method for producing an optically active ±-amino acid in high yield and in a highly enantioselective manner, to provide a simple production method of an optically active ±,±-disubstituted ±-amino acid, and to provide an intermediate useful for the above production methods of an optically active ±-amino acid and an optically active ±,±-disubstituted ±-amino acid. The present invention provides a production method of an optically active ±-amino acid or a salt thereof, the production method comprising introducing a substituent into the ± carbon in the ±-amino acid moiety of a metal complex represented by the following Formula (1): by an alkylation reaction, an aldol reaction, the Michael reaction, or the Mannich reaction, and releasing an optically pure ±-amino acid enantiomer or a salt thereof by acid decomposition of the metal complex.

Synthesis of quaternary α-methyl α-amino acids by asymmetric alkylation of pseudoephenamine alaninamide pivaldimine

The utility of pseudoephenamine as a chiral auxiliary for the alkylative construction of quaternary α-methyl α-amino acids is demonstrated. The method is notable for the high diastereoselectivities of the alkylation reactions, for its versatility with respect to electrophilic substrate partners, and for its mild hydrolysis conditions, which provide α-amino acids without salt contaminants. Alternatively, α-amino esters can be obtained by direct alcoholysis.

Enantiocatalytic activity of substituted 5-benzyl-2-(pyridine-2-yl) imidazolidine-4-one ligands

Currently, asymmetric synthesis represents one of the main streams of organic synthesis. Although an extensive research has been carried out in this area, the synthesis of chiral compounds with the required enantiomeric purity is still a challenging issue. Herein, we focus on the preparation of new enantioselective catalysts based on pyridine-imidazolidinones. The substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-ones 5-8 were prepared by condensation of chiral amino acid amides (α-methylDOPA and α- methylphenylalanine) with 2-acetylpyridine and pyridine-2-carbaldehyde. The individual isomers of the described ligands 5-8 were separated chromatographically. The copper(II) complexes of these chiral ligands were studied as enantioselective catalysts for the asymmetric Henry reaction of substituted aldehydes with nitromethane or nitroethane. The ligands containing a methyl group at the 2-position of the imidazolidinone ring 6a and 8a exhibit a high degree of enantioselectivity (up to 91% ee). The nitroaldols derived from nitroethane (2-nitropropan-1-ols) were obtained with a comparable enantiomeric purity to derivatives of 2-nitroethanol. This group of ligands represents a new and promising class of enantioselective catalysts, which deserve further attention.

Non-enzymatic diastereoselective asymmetric desymmetrization of 2-benzylserinols giving optically active 4-benzyl-4-hydroxymethyl-2- oxazolidinones: Asymmetric syntheses of α-(hydroxymethyl)phenylalanine, N-Boc-α-methylphenylalanine, cericlamine and BIRT-377

A reaction of (S)-2-benzyl-2-(α-methylbenzyl)amino-1,3-propanediol (S)-4a and 2-chloroethyl chloroformate, and the subsequent addition of DBU gave (4R,αS)-4-benzyl-4-hydroxymethyl-3-(α-methylbenzyl)-2-oxazolidinone (4R)-5a (92% de) via a diastereoselective asymmetric desymmetrization process. Debenzylation of (4R)-5a using trifluoromethanesulfonic acid and anisole in MeNO2 gave (R)-4-benzyl-4-hydroxymethyl-2-oxazolidinone (R)-15a, which was converted into (R)-(α-hydroxymethyl)phenylalanine (7) in two steps. N-Boc-α-methylphenylalanine (8), cericlami0ne (9) and BIRT-377 (10) were also synthesized using these asymmetric desymmetrization and debenzylation.

TRICYCLIC BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

The present invention is directed to tricyclic compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The inv

TERTIARY CARBINAMINES HAVING SUBSTITUTED HETEROCYCLES, WHICH ARE ACTIVE AS INHIBITORS OF BETA-SECRETASE, FOR THE TREATMENT OF ALZHEIMER'S DISEASE

The present invention is directed to tertiary carbinamine compounds having substituted heterocycles, which are inhibitors of the beta-secretase enzyme, and are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alz

AMINOMETHYL BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

The present invention is directed to aminomethyl compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is als

In-depth study of tripeptide-based α-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1′ subsite and its implications to structure-based drug design

Thrombin inhibitors are potentially useful in medicine for their anticoagulant and antithrombotic effects. We synthesized and evaluated diverse heterocycle-activated ketones based on the D-Phe-Pro-Arg, and related thrombin active-site recognition motifs, as candidate inhibitors. The peptide-based α-ketoheterocycles were typically prepared by either an imidate or a Weinreb amide route (Schemes 1 and 2), the latter of which proved to be more general. Test compounds were generally assayed for inhibition of human α-thrombin and bovine trypsin. From a structure-based design standpoint, the heterocycle allows one to explore and adjust interactions within the S1′ subsite of thrombin. The preferred α-ketoheterocycle is a π-rich 2-substituted azole with at least two heteroatoms proximal to the carbon bearing the keto group, and a preferred thrombin inhibitor is 2-ketobenzothiazole 3, with a potent Ki value of 0.2 nM and ca. 15-fold selectivity over trypsin. 2-Ketobenzothiazole 13 exhibited exceedingly potent thrombin inhibition (Ki = 0.000 65 nM; slow tight binding). Several α-ketoheterocycles had thrombin Ki values in the range 0.1-400 nM. The "Arg" unit in the α-ketoheterocycles can be sensitive to stereomutation under mildy basic conditions. For example, 2-ketothiazoles 4 and 59 readily epimerize at pH 7.4, although they are fairly stable stereochemically at pH 3-4; thus, suitable conditions had to be selected for the enzymatic assays. Lead D-Phe-Pro-Arg 2-benzothiazoles 3, 4, and 68 displayed good selectivity for thrombin over other key coagulation enzymes (e.g., factor Xa, plasmin, protein Ca, uPA, tPA, and streptokinase); however, their selectivity for thrombin over trypsin was modest (50 = 30-40 nM). They also proved to be potent anticoagulant/ antithrombotic agents in vivo on intravenous administration, as determined in the canine arteriovenous shunt (ED50 = 0.45-0.65 mg/kg) and the rabbit deep vein thrombosis (ED50 = 0.1-0.4 mg/kg) models. Intravenous administration of 3, and several analogues, to guinea pigs caused hypotension and electrocardiogram abnormalities. Such cardiovascular side effects were also observed with some nonguanidine inhibitors and inhibitors having recognition motifs other than D-Phe-Pro-Arg. 2-Benzothiazolecarboxylates 4 and 68 exhibited significantly diminished cardiovascular side effects, and benzothiazolecarboxylic acid 4 had the best profile with respect to therapeutic index. The X-ray crystal structures of the ternary complexes 3-thrombin-hirugen and 4-thrombin-hirugen depict novel interactions in the S1′ region, with the benzothiazole ring forming a hydrogen bond with His-57 and an aromatic stacking interaction with Trp-60D of thrombin's insertion loop. The benzothiazole ring of 3 displaces the Lys-60F side chain into a U-shaped gauche conformation, whereas the benzothiazole carboxylate of 4 forms a salt bridge with the side chain of Lys-60F such that it adopts an extended anti conformation. Since 3 has a 10-fold greater affinity for thrombin than does 4, any increase in binding energy resulting from this salt bridge is apparently offset by perturbations across the enzyme (viz. Figure 4). The increased affinity and selectivity of 2-ketobenzothiazole inhibitors, such as 3, may be primarily due to the aromatic stacking interaction with Trp-60D. However, energy contour calculations with the computer program GRID also indicate a favorable interaction between the benzothiazole sulfur atom and a hydrophobic patch on the surface of thrombin.