224434-01-9

Upstream product

• 459-57-4 4-fluorobenzaldehyde 
• 130632-07-4 (E)-1-(4-fluorophenyl)-N-(4-methoxyphenyl)methanimine 
• 19883-57-9 (S)-2-amino-2-(4-fluorophenyl)acetic acid 
• 1139818-79-3 (S)-tert-butyl 1-(4-fluorophenyl)-2-hydroxyethylcarbamate 
• 935534-38-6 2-((tert-butyldimethylsilyl)oxy)-1-(4-fluorophenyl)ethanone 
• 1312718-97-0 (Rs)-N-(2-(tert-butyldimethylsilyloxy)-1-(4-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide 
• 1312719-09-7 (Rs,1S)-N-(2-(tert-butyldimethylsilyloxy)-1-(4-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 1160850-91-8 N-boc-4'-fluoro-(S)-phenylglycine methyl ester 
• 17951-22-3 1-(4-fluorophenyl)ethane-1,2-diol 
• 403-31-6 4-fluoro-2-hydroxy-acetophenone 
• 18511-62-1 4-fluorostyrene oxide 
• 140373-17-7 α-hydroxymethyl-4-fluorobenzylamine 
• 199392-90-0 [(S)-1-(4-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid benzyl ester 

Downstream Products

• 1160850-98-5 C₉H₁₀FNO 
• 1391432-97-5 C₁₇H₁₃FN₂O₆ 
• 1357079-98-1 (1S)-2-azetidin-1-yl-1-(4-fluorophenyl)ethanamine 
• 1139818-79-3 (S)-tert-butyl 1-(4-fluorophenyl)-2-hydroxyethylcarbamate 

Relevant academic research and scientific papers

Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase

Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg?1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L?1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.

Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols

Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely present in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as by-products, using NAD(P)H as a cofactor under mild conditions, but hydroxy ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19-99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9.0 and the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model β-hydroxy ketone leading to β-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.

Enantioselective Copper Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution

The copper(I) catalyzed alkyne-azide cycloaddition (CuAAC), a click reaction, is one of the most powerful catalytic reactions developed during the last two decades. Conducting CuAAC enantioselectively would add a third dimension to this reaction and would

Asymmetric ring opening of racemic epoxides for enantioselective synthesis of (S)-β-amino alcohols by a cofactor self-sufficient cascade biocatalysis system

A novel one-pot epoxide hydrolase/alcohol dehydrogenase/transaminase cascade process for the asymmetric ring opening of racemic epoxides to enantiopure β-amino alcohols is reported. The product (S)-β-amino alcohols were obtained in 97-99% ee and 79-99% conversion from readily available racemic epoxides.

SERINE/THREONINE KINASE INHIBITORS

Compounds having the formula I wherein R2, X and Z as defined herein are inhibitors of ERK kinase. Also disclosed are compositions and methods for treating hyperproliferative disorders.

Novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P2 position

Recently, we reported substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. We also designed and

A general asymmetric synthesis of phenylglycinols

Hydride reduction and deprotection of siloxymethyl sulfinimines 2 reliably furnished chiral phenylglycinols 1 or 10 in high overall yield and enantiomeric purity.

Significance of interactions of BACE1-Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold

Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1.

NOVEL B1 BRADYKININ RECEPTOR ANTAGONISTS

The invention encompasses novel compounds of a formula I and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for treatment of diseases mediated by B1 bradykinin receptor.

PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES

Compounds of formula (I): and their use in the inhibition of Trk activity are described.