26782-75-2

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(-)-2-Bromo-3-methylbutyric acid is used as a key intermediate in the synthesis of ferroelectric liquid crystal derivatives. These derivatives are valuable for their potential applications in the development of advanced materials with unique electro-optic properties.
Used in Enzyme Inhibition:
In the field of biochemistry and drug discovery, (S)-(-)-2-Bromo-3-methylbutyric acid serves as a building block for the creation of proline-valine pseudo dipeptides. These pseudo dipeptides are potent inhibitors of α-chymotrypsin, an enzyme involved in the digestion of proteins. The inhibition of this enzyme can have therapeutic applications in controlling inflammation and other conditions.
Used in Peptide Conformation Research:
(S)-(-)-2-Bromo-3-methylbutyric acid is also utilized in the preparation of β-turn peptidomimetics. These peptidomimetics are designed to mimic the β-turn structure found in proteins, which is essential for maintaining their three-dimensional conformation and function. The study and manipulation of peptide conformations can lead to the development of new drugs and a better understanding of protein folding diseases.

InChI:InChI=1/C5H9BrO2/c1-3(2)4(6)5(7)8/h3-4H,1-2H3,(H,7,8)/t4-/m0/s1

Upstream product

• 10323-40-7 2-bromoisovaleric acid 
• 640-68-6 D-Val-OH 
• 167823-33-8 1,2;5,6-di-O-(1-methylethylidene)-α-D-glucofuranosyl-2-bromo-3-methyl butanoate 
• 503-74-2 3-methylbutyric acid 
• 609-12-1 ethyl 2-bromoisovalerate 
• 169320-29-0 (R)-2-bromo-3-methylbutanoic acid (1:1) N-(1-methylethyl)-2-propanamine 
• 161661-13-8 1-<1,2;5,6-di-O-(1-methylethylidene)-α-D-glucofuranosyloxy>-1-trimethylsilyloxy-3-methyl-but-1-ene 
• 139193-62-7 1,2;5,6-di-O-(1-methylethylidene)-α-D-glucofuranosyl 3-methyl butanoate 
• 27109-47-3 2-bromoisovaleryl chloride 

Downstream Products

• 27109-49-5 (+)-Bromisoval 
• 54837-20-6 N-benzyloxy-L-valine 
• 27109-47-3 (R)-α-Bromoisopentanoic acid chloride 
• 27318-02-1 (S)-α-Bromoisopentanoic acid chloride 
• 578742-53-7 (R)-2-bromoisovaleric acid dicyclohexylamine salt 
• 4026-18-0 2-hydroxy-3-methylbutanoic acid 
• 516-06-3 D,L-valine 
• 439688-98-9 N-(3-azido-4-methyl-2-triethylsilanyloxy-hexyl)-2-bromo-N-{2-(tert-butyl-diphenyl-silanyloxy)-1-[(trityl-carbamoyl)-methyl]-ethyl}-3-methyl-butyramide 
• 516491-42-2 2-{[1-((R)-2-Bromo-3-methyl-butyrylamino)-cyclopentanecarbonyl]-amino}-3-(6-phenyl-pyridin-3-yl)-propionic acid ethyl ester 
• 516491-68-2 2-{[1-((R)-2-Bromo-3-methyl-butyrylamino)-cyclopentanecarbonyl]-amino}-3-[6-(3-nitro-phenyl)-pyridin-3-yl]-propionic acid ethyl ester 
• 957199-60-9 (S)-2-benzoylthio-3-methylbutanoic acid 
• 920339-26-0 (R)-2-bromo-3-methyl-N-phenylbutyramide 
• 169320-29-0 (R)-2-bromo-3-methylbutanoic acid (1:1) N-(1-methylethyl)-2-propanamine 
• 78445-41-7 (R)-2-(4-trifluoromethylphenylamino)-3-methylbutanoic acid 

Relevant academic research and scientific papers

A novel lipase from Aspergillus oryzae catalyzed resolution of (R,S)-ethyl 2-bromoisovalerate

In this study, a novel lipase M5 derived from Aspergillus oryzae WZ007 was prone to exhibit high hydrolytic activity and stereoselectivity towards racemic substrate (R,S)-ethyl 2-bromoisovalerate. (R)-ethyl 2-bromoisovalerate was obtained by enzymatic resolution, which is the key chiral intermediate for highly efficient enantiomerically fluvalinate. The results showed that the enzymatic reaction was carried out in 120mM racemic substrate for 3 hours, the enantiomeric excess reached 98.6%, the conversion was 51.7%, and E value above 120. Therefore, the novel lipase M5 has the ability to efficiently produce (R)-ethyl 2-bromoisovalerate, which greatly reduces the industrial production cost of the highly efficient counterpart of fluvalinate.

Ribosomal Synthesis of Backbone-Cyclic Peptides Compatible with in Vitro Display

Backbone-cyclic peptides are an attractive class for therapeutic development. However, in vitro display technologies coupled with ribosomal synthesis are intrinsically inapplicable to such "phenotypes" because of loss of the C-terminal peptide region linking to "genotype". Here, we report a methodology enabling the display of backbone-cyclic peptides. To achieve this, genetic code reprogramming was utilized to implement a rearrangement strategy involving the ribosomal incorporation of a designer initiator containing a thiazolidine-protected cysteine and 2-chloroacetoamide (ClAc) side chain, followed by an α-thio acid and cysteine at downstream positions. Upon expression of the linear peptide, spontaneous thioester rearrangement occurs between the α-thioester and the thiol group of the cysteine, liberating the α-thio group and resulting in cross-linking to the upstream ClAc side-chain group. Then selective deprotection of the thiazolidine-protected cysteine immediately promotes intramolecular native chemical ligation, as demonstrated for various sequences and ring sizes. In this approach, the backbone-cyclic peptides retain their C-terminal peptide regions via the side-chain thioether covalent linkage, making them compatible with in vitro display.

Solid phase synthesis of 1,3,4-oxadiazin-5 (6R)-one and 1,3,4-oxadiazol-2-one scaffolds from acyl hydrazides

Solid phase synthesis of 1,3,4-oxadiazin-5(6R)-one and 1,3,4-oxadiazol-2-one scaffolds from resin-bound acyl hydrazides is described. We demonstrate here that the reactions of resin-bound aryl or hetero-aromatic acyl hydrazides with 2-substituted-2-bromoacetic acids and 4-nitrophenyl chloroformate and subsequent treatment with DIEA lead to intramolecular cyclization reactions to produce six-membered 1,3,4-oxadiazin-5(6R)-ones and five-membered 1,3,4-oxadiazol-2-ones, respectively. We also show that acyl hydrazide-derived 1,3,4-oxadiazol-2-ones may be useful serine hydrolase inhibitors. This journal is

Discovery of a potent, orally active 11β-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: Identification of (S)-2-((1 S,2 S,4 R)-Bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5 H)-one (AMG 221)

Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11β-HSD1 inhibitors. However, the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer. A methyl group was added to the C-5 position to eliminate epimerization, leading to the discovery of (S)-2-((1S,2S,4R)-bicyclo[2.2.1] heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). This compound decreased fed blood glucose and insulin levels and reduced body weight in diet-induced obesity mice.

A novel series of parenteral cephalosporins exhibiting potent activities against Pseudomonas aeruginosa and other Gram-negative pathogens: Synthesis and structure-activity relationships

A series of 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(carboxymethoxyimino)acetamido]cephalosporins bearing a 1-(substituted)-1H-pyrrolo[3,2-b]pyridinium group at C-3′ position was synthesized and their in vitro antibacterial activities against Pseudomonas aeruginosa and other Gram-negative pathogens were evaluated. Among the cephalosporins prepared, 7β-[2-(2-amino-5-chlorothiazol-4yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]cephalosporins (42d) showed potent antibacterial activities against P. aeruginosa and other Gram-negative pathogens including the strains which produce class C β-lactamase and extended spectrum β-lactamase (ESBL). These results imply that both the Cl atom on the C-7 aminothiazole moiety and the α-substituent at the iminoether moiety are essential for the stability against β-lactamase and the potent activity against Gram-negative bacteria including P. aeruginosa.

Synthesis and structures of (S)- and (R)-2-[3-cyano-4-(2-thienyl)-5,6,7, 8-tetrahydroquinolin-2-ylsulfanyl]-3-methyl-N-phenylbutyramide

(S)- and (R)-2-[3-cyano-4-(2-thienyl)-5,6,7,8-tetrahydroquinolin-2- ylsulfanyl]-N-phenyl-3-methylbutyramide (1a and 1b) were prepared from 2-thiophenaldehyde and D- and L-valines, respectively, and their crystal structures were elucidated by X-ray crystallography.

PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 2-HALOGENO- CARBOXYLIC ACIDS

The invention provides processes for producing efficiently optically active 2-halogenocarboxylic acids useful in the preparation of drugs or the like and salts thereof with amines. Specifically, an optically active 2-halogenocarboxylic acid is produced by halogenating an optically active amino acid in water in the presence of a hydrophobic organic solvent and nitrous acid with the configuration retained and with the racemization inhibited through the removal of 2-hydroxy- bromocarboxylic acid formed as a by-product; the obtained optically active 2-halogenocarboxylic acid is transferred to an aqueous phase by converting it into a salt thereof with a base, followed by the removal of the organic phase; and the optically active 2-halogenocarboxylic acid is transferred again to an organic solvent phase, followed by the removal of the aqueous phase, whereby an optically active 2-halogenocarboxylic acid is obtained through the removal of a halogen component. Further, a high-quality salt of an optically active 2-halogenocarboxylic acid with an amine can be obtained by a crystallization method wherein the amine is added over the period of 1/2 hour or longer either continuously or in portions and/or wherein the crystallization solvent consists of a hydrophobic organic solvent and a hydrophilic organic solvent.

Mercaptoacetylamide derivatives, a process for their preparation and their use

This invention discloses and claims a series of mercaptoacetylamide derivatives of formula I. Also disclosed and claimed are pharmaceutical compositions incorporating these compounds and processes for preparing said compounds. The use of said compounds for inhibition of the enzymes angiotensin converting enzyme and neutral endopeptidase, and for the treatment of hypertension and congestive heart failure are also disclosed and claimed.

Synthesis and biological activity of novel potent endothelin-converting enzyme-1 inhibitors

Through directed screening of metalloprotease inhibitors, CGS 30084 (1) has been identified as a potent endothelin-converting enzyme-1 (ECE-1) inhibitor in vitro (IC50 = 77 nM). Herein we report the syntheses and biological activities of analogues derived from this lead, based on modifications of the biphenyl moiety. Compound 10, the thioacetate methyl ester prodrug derivative of compound 6m, was found to be an orally active and potent inhibitor of ECE-1 activity in rats.

Efficient large scale preparation of neutral endopeptidase/ angiotensin-converting enzyme dual inhibitor CGS30440

The development and piloting of a potential manufacturing process for ACE/NEP dual inhibitor CGS30440 is described. The synthesis proceeds sequentially from 1-aminocyclopentanecarboxylic acid via N-protection, peptide coupling with L-tyrosine ethyl ester, O-methylation of N-protected [(1-amino-1-cyclopentyl)carbonyl]-L-tyrosine ethyl ester, N-deprotection, peptide coupling of [(1-amino-1-cyclopentyl)carbonyl]-O-methyl-L-tyrosine ethyl ester with D-2-bromo-3-methylbutyric acid, and final displacement of bromide with thioacetate. This approach is superior to shorter Discovery routes based upon final peptide coupling of L-2-(acetylthio)-3-methylbutanoic acid to [(1-amino-1-cyclopentyl)carbonyl]-O-methyl-L-tyrosine ethyl ester.