565-74-2

Usage

Uses

Used in Biochemical Research:
2-Bromo-3-methylbutyric acid is used as a research compound for studying the conjugation of glutathione (GSH) with (R)-and (S)-α-bromoisovaleric acid (BI) in rats. This research is crucial for understanding the metabolic pathways and detoxification mechanisms involving halogenated compounds in biological systems.
Used in Pharmaceutical Synthesis:
2-Bromo-3-methylbutyric acid is utilized in the preparation of optically active N-methylvalines, which are important building blocks for the synthesis of various pharmaceuticals and bioactive molecules. The optical activity of these compounds is essential for their biological activity, making 2-Bromo-3-methylbutyric acid a valuable precursor in the development of enantioselective synthetic routes.

InChI:InChI=1/C5H9BrO2/c1-3(2)4(6)5(7)8/h3-4H,1-2H3,(H,7,8)/p-1/t4-/m1/s1

Upstream product

• 503-74-2 3-methylbutyric acid 
• 64932-36-1 2-bromo-3-methyl-butyraldehyde 
• 3252-43-5 dibromoacetonitrile 
• 78-84-2 isobutyraldehyde 
• 42454-71-7 bromo-isopropyl-malonic acid 
• 861319-78-0 1-ethoxy-2-bromo-1-chloro-3-methyl-butane 
• 590-86-3 isovaleraldehyde 
• 609-36-9 rac-Pro-OH 
• 10323-40-7 2-bromoisovaleric acid 
• 640-68-6 D-Val-OH 
• 27109-47-3 2-bromoisovaleryl chloride 
• 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 

Downstream Products

• 609-12-1 ethyl 2-bromoisovalerate 
• 66018-25-5 2-methoxy-3-methylbutanoic acid 
• 541-47-9 3-Methylbutenoic acid 
• 4026-18-0 2-hydroxy-3-methylbutanoic acid 
• 76792-22-8 (R)-2-bromoisovaleric acid 
• 27109-47-3 2-bromoisovaleryl chloride 
• 19866-38-7 α-hydrazino-isovaleric acid 
• 516-06-3 D,L-valine 
• 15206-52-7 N,N-dimethylvaline 
• 3805-17-2 2-amino-5-isopropyl-thiazol-4-one 
• 98275-78-6 2-(1-Methyl-hydrazino)-isovaleriansaeure 
• 80532-76-9 (E)-methyl 2-isopropyl-3-methyl-3-phenyl-2-oxiranecarboxylate 
• 110351-27-4 methyl 2-benzyloxy-3-methylbutanoate 
• 80532-77-0 2-isopropyl-3,3-diphenyl-2-oxiranecarboxylic acid 

Relevant academic research and scientific papers

O-to-S Substitution Enables Dovetailing Conflicting Cyclizability, Polymerizability, and Recyclability: Dithiolactone vs. Dilactone

Developing chemically recyclable polymers represents a greener alternative to landfill and incineration and offers a closed-loop strategy toward a circular materials economy. However, the synthesis of chemically recyclable polymers is still plagued with certain fundamental limitations, including trade-offs between the monomer's cyclizability and polymerizability, as well as between polymer's depolymerizability and properties. Here we describe the subtle O-to-S substitution, dithiolactone monomers derived from abundant feedstock α-amino acids can demonstrate appealing chemical properties different from those of dilactone, including accelerated ring closure, augmented kinetics polymerizability, high depolymerizability and selectivity, and thus constitute a unique class of polythioester materials exhibiting controlled molecular weight (up to 100.5 kDa), atactic yet high crystallinity, structurally diversity, and chemical recyclability. These polythioesters well addresses the formidable challenges of developing chemically recyclable polymers by having an unusual set of desired properties, including easy-to-make monomer from ubiquitous feedstock, and high polymerizability, crystallinity and precise tunability of physicochemical performance, as well as high depolymerizability and selectivity. Computational studies explain why O-to-S modification of polymer backbone enables dovetailing desirable, but conflicting, performance into one polymer structure.

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.

Benzo six-membered nitrogen heterocyclic compound, preparation method and applications

The present invention provides a benzo six-membered nitrogen heterocyclic compound, a preparation method and applications, wherein the benzo six-membered nitrogen heterocyclic compound has a structurerepresented by a formula I or formula II, and can effectively inhibit the bromine domain receptor and effectively inhibit the proliferation of cancer cells. Compared with the existing reported structure types, the compound of the present invention has different binding mode, has high inhibitory activity, can be used as a drug for treating cancer, cell proliferation disorders, inflammatory diseases, autoimmune diseases, septicemia and viral infections, and has good application prospects and high application value.

Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer

The bromodomain and extra-terminal proteins (BET) have emerged as promising therapeutic targets for the treatment of castration-resistant prostate cancer (CRPC). We report the design, synthesis and evaluation of a new series of benzoxazinone-containing 3,5-dimethylisoxazole derivatives as selective BET inhibitors. One of the new compounds, (R)-12 (Y02234), binds to BRD4(1) with a Kd value of 110 nM and blocks bromodomain and acetyl lysine interactions with an IC50 value of 100 nM. It also exhibits selectivity for BET over non-BET bromodomain proteins and demonstrates reasonable anti-proliferation and colony formation inhibition effect in prostate cancer cell lines such as 22Rv1 and C4-2B. The BRD4 inhibitor (R)-12 also significantly suppresses the expression of ERG, Myc and AR target gene PSA at the mRNA level in prostate cancer cells. Treatment with (R)-12 significantly suppresses the tumor growth of prostate cancer (TGI = 70%) in a 22Rv1-derived xenograft model. These data suggest that compound (R)-12 is a promising lead compound for the development of a new class of therapeutics for the treatment of CRPC.

Cobalt-Catalyzed Cross-Coupling of α-Bromo Amides with Grignard Reagents

A cobalt-catalyzed cross-coupling between α-bromo amides and Grignard reagents is disclosed. The reaction is general and allows access to a large variety of α-aryl and β,γ-unsaturated amides. Some mechanistic investigations have been undertaken to determine the nature of the intermediate species.

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

Synthesis of enantiomerically enriched-bromonitriles from amino acids

Two methods were investigated for the preparation of six chiral-bromonitriles with different optic purities. The nitrous deamination of amino acids gives-bromoacids, which react with chlorosulfonyl isocyanate followed by triethylamine to afford-bromonitriles with moderate enantiomeric excess. However, the dehydration of corresponding-bromoamids using thionyl chloride gives-bromonitriles with good enantiomeric excess up to 94%. The use of phosphoryl chloride instead of thionyl chloride results in more than 30% racemization as determined by high-performance liquid chromatograpic analysis.

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.

Synthesis of α-bromoisovaleric acid in the poliphosphoric acid medium

Bromination of isovaleric acid with bromine in the polyphosphoric acid mediumis was studied, regularities of the process including influence of the polyphosphoric acid composition were revealed, the process was shown technologically attractive for the organization of industrial manufacturing of α-bromoisovaleric acid.