98648-05-6

Upstream product

• 79-37-8 oxalyl dichloride 
• 17996-12-2 N-benzyloxycarbonyl-6-amino-1-hexanol 
• 7087-68-5 N-ethyl-N,N-diisopropylamine 
• 4048-33-3 6-amino-1-hexanol 
• 501-53-1 benzyl chloroformate 
• 1947-00-8 6-(benzyloxycarbonylamino)hexanoic acid 
• 25580-87-4 methyl 6-(((benzyloxy)carbonyl)amino)hexanoate 
• 60-32-2 6-aminohexanoic acid 
• 62252-26-0 JLK 6 

Downstream Products

• 957829-63-9 10-(6-benzyloxycarbonylamino-hexyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-tricarboxylic acid tri-tert-butyl ester 
• 179760-69-1 [6-(2-hydroxy-ethylamino)-hexyl]-carbamic acid benzyl ester 
• 1198782-08-9 1,15-bis[4,7,10-tris(t-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-6-{[N-cyclohexyl-1-(N-Cbz-5-aminopentyl)]carboxamidomethyl}-2,7,14-trioxo-3,6,13-triazapentadecane 
• 1318692-88-4 6-[6-(benzyloxycarbonylamino)hexylamino]-2-cyanobenzothiazole 
• 1290118-53-4 C₄₂H₆₆N₄O₁₂ 
• 111497-08-6 7-(((benzyloxy)carbonyl)amino)-2-hydroxyheptanoic acid 
• 1015255-72-7 benzyl-7-(benzylamino)-6,7-dioxoheptylcarbamate 
• 1000886-00-9 methyl-N-[2-(1-[benzyl(4-hydroxybutyl)amino]-6-{[(benzyloxy)carbonyl]amino}hexyl)-3-oxa-1-azaspiro[4.5]dec-1-en-4-ylidene]glycinate 
• 929875-46-7 (benzyl-{2-[6-benzyloxycarbonylamino-1-({6-[(2-hydroxy-ethylcarbamoyl)-methyl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl}-amino)-hexyl]-oxazol-5-yl}-amino)-acetic acid methyl ester 

Relevant academic research and scientific papers

Enolesters as chain end-functionalizing agents for the living ring opening metathesis polymerization

Functional enolethers have previously been used to introduce functional end groups at the chain end of ruthenium carbene complex initiated living ring opening metathesis polymers. Here, we investigated whether the weaker π-donating enolesters could equally be used in regio selective reactions with ruthenium carbene complexes and thus as polymer end-functionalization reagents. Enolesters such as vinyl acetate, butenyl acetate, 3-(4-(tert-butoxy)phenyl)propenyl acetate and 6-(((benzyloxy)carbonyl)amino)hex-1-en-1-yl acetate were used as living ROMP terminating agents. All gave the expected end groups proving that enolesters are synthetically easily accessible targets for living ROMP end-functionalization.

Metal-free one-pot α-carboxylation of primary alcohols

An efficient metal-free procedure for the formal α-carboxylation of primary alcohols has been developed. The method involves a one-pot oxidation/Passerini/hydrolysis sequence and provides access to α-hydroxy acids bearing a broad range of functional groups. A minor modification to the reaction conditions extends the range of accessible products to α-hydroxy esters.

Chloroperoxidase-catalyzed amino alcohol oxidation: Substrate specificity and novel strategy for the synthesis of N-Cbz-3-aminopropanal

The ability of chloroperoxidase (CPO) to catalyze amino alcohol oxidations was investigated. The oxidations of compounds with different configurations with respect to the amine position towards hydroxyl – using H2O2 and tert-butyl hydroperoxide (t-BuOOH) – were analyzed in terms of the initial reaction rate, substrate conversion, and CPO operational stability. It was observed that the further the amino group from the hydroxyl, the lower the initial reaction rate. The effect of the amino-protecting group and other substituents (i.e., methyl and hydroxyl) was also examined, revealing an increase in steric hindrance due to the effect of bulky substituents. The observed reaction rates were higher with t-BuOOH, whereas CPO was more stable with H2O2. Moreover, CPO stability had to be determined case by case as the enzyme activity was modulated by the substrate. The oxidation of N-Cbz-3-aminopropanol (Cbz, carboxybenzyl) to N-Cbz-3-aminopropanal was investigated. Main operational conditions such as the reaction medium, initial amino alcohol concentration, and peroxide nature were studied. The reaction kinetics was determined, and no substrate inhibition was observed. By-products from a chemical reaction between the formed amino aldehyde and the peroxide were identified, and a novel reaction mechanism was proposed. Finally, the biotransformation was achieved by reducing side reactions and identifying the key factors to be addressed to further optimize the product yield.

UBA5 INHIBITORS

The present disclosure relates to compounds of the Formula (I), which are UBA5 inhibitors.

Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds

The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds. Strong as an ox: The highly chemoselective aerobic oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has been achieved by using 2-azaadamantane N-oxyl (AZADO)/copper catalysis. This catalytic system oxidizes not only alcohols with tertiary amino groups but also those with secondary and primary amines in good to high yield at ambient temperature in air. bpy=2,2-bipyridyl, DMAP=4-(N,N-dimethylamino)pyridine.

Further characterization of a putative serine protease contributing to the γ-secretase cleavage of β-amyloid precursor protein

The 3-alkoxy-7-amino-4-chloro-isocoumarins JLK-6 and JLK-2 have been shown to markedly reduce the production of Amyloid β-peptide (Aβ) by Amyloid-β Precursor Protein (APP) expressing HEK293 cells by affecting the γ-secretase cleavage of APP, with no effect on the cleavage of the Notch receptor. This suggested that these compounds do not directly inhibit the presenilin-dependent γ-secretase complex but more likely interfere with an upstream target involved in γ-secretase-associated pathway. The mechanism of action of these compounds is unknown and there are high fundamental and therapeutical interests to unravel their target. Isocoumarin compounds were previously shown to behave as potent mechanism-based irreversible inhibitors of serine proteases, suggesting that the JLK-directed target could belong to such enzyme family. To get further insight into structure-activity relationships and to develop more potent isocoumarin derivatives, we have synthesized and evaluated a series of isocoumarin analogues with modifications at positions 3, 4 and 7. In particular, the 7-amino group was substituted with either acyl, urethane, alkyl or aryl groups, which could represent additional interaction sites. Altogether, the results highlighted the essential integrity of the 3-alkoxy-7-amino-4-chloro-isocoumarin scaffold for Aβ-lowering activity and supported the involvement of a serine protease, or may be more generally, a serine hydrolase. The newly reported 7-N-alkyl series produced the most active compounds with an IC50 between 10 and 30 μM. Finally, we also explored peptide boronates, a series of reversible serine protease inhibitors, previously shown to also lower cellular Aβ production. The presented data suggested they could act on the same target or interfere with the same pathway as isocoumarins derivatives.

Aminoluciferins as functional bioluminogenic substrates of firefly luciferase

Firefly luciferase is widely used as a reporter gene in assays to study gene expression, gene delivery, and so on because of its extremely high signal-to-noise ratio. The availability of a range of bioluminogenic substrates would greatly extend the applicability of the luciferin-luciferase system. Herein, we describe a design concept for functional bioluminogenic substrates based on the aminoluciferin (AL) scaffold, together with a convenient, high-yield method for synthesizing N-alkylated ALs. We confirmed the usefulness of ALs as bioluminogenic substrates by synthesizing three probes. The first was a conjugate of AL with glutamate, Glu-AL. When Glu-AL, the first membrane-impermeable bioluminogenic substrate of luciferases, was applied to cells transfected with luciferase, luminescence was not observed; that is, by using Glu-AL, we can distinguish between intracellular and extracellular events. The second was Cy5-AL, which consisted of Cy5, a near-infrared (NIR) cyanine fluorescent dye, and AL, and emitted NIR light. When Cy5-AL reacted with luciferase, luminescence derived from Cy5 was observed as a result of bioluminescence resonance energy transfer (BRET) from AL to Cy5. The NIR emission wavelength would allow a signal to be observed from deeper tissues in bioluminescence in vivo imaging. The third was biotin-DEVD-AL (DEVD=the amino acid sequence Asp-Glu-Val-Asp), which employed a caspase-3 substrate peptide as a switch to control the accessibility of the substrate to luciferase, and could detect the activity of caspase-3 in a time-dependent manner. This generalized design strategy should be applicable to other proteases. Our results indicate that the AL scaffold is appropriate for a range of functional luminophores and represents a useful alternative substrate to luciferin.

Effective methods for the biotinylation of azamacrocycles

(Chemical Equation Presented) The biotin-(strept)avidin interaction remains a gold standard of model biological recognition events. The biotinylation of azamacrocycles permits the investigation of signal transduction between this recognition event and the

ERYTHROMYCIN A 9-0-OXIME DERIVATIVES ENDOWED WITH ANTIBIOTIC ACTIVITY

PCT No. PCT/EP95/04815 Sec. 371 Date May 16, 1997 Sec. 102(e) Date May 16, 1997 PCT Filed Dec. 7, 1995 PCT Pub. No. WO96/18633 PCT Pub. Date Jun. 20, 1996Erythromycin 9-oxime derivatives wherein a phenyl or heterocylic group is attached indirectly to the 9-position of erythromycin A through an alkylene diamine bridging member. These compounds exhibit broad spectrum antibiotic activity.

4-SUBSTITUTED 2-AMINOALK-3-ENOIC ACIDS

Substituted 2-aminoalk-3-enoic acid derivative of formula I STR1 wherein R 1 is an aliphatic hydrocarbon radical that is substituted by optionally acylated or aliphatically or araliphatically etherified hydroxy, by halogen, by optionally acylated and/or aliphatically substituted amino or by an aza-, diaza-, azoxa-or oxa-cycloaliphatic radical, or is an oxacycloaliphatic hydrocarbon radical bonded via a carbon atom, or is an optionally aliphatically N-substituted or N-acylated azacycloaliphatic hydrocarbon radical, and R. sub.2 is free or esterified carboxy, and their salts exhibit NMDA-antagonistic properties and are useful as active ingredients of anticonvulsive medicaments.