Modern heterogeneous catalysts for aerobic alcohol oxidation: the state of art.

Hypervalent iodine compounds are viable reagents for the oxidation of N,N-disubstituted hydroxylamines to corresponding nitrones, with IBX performing best. The procedure is very simple and user-friendly affords target high efficiency regioselectivity, highlighting as reagent choice preparation aldonitrones from nonsymmetric hydroxylamines. Evidence a mechanism involving nitrogen coordination has been collected.

Abstract A collection of carbohydrate‐derived iminosugars belonging to three structurally diversified sub‐classes (polyhydroxylated pyrrolidines, piperidines, and pyrrolizidines) was evaluated for inhibition human acid β‐glucosidase (glucocerebrosidase, GCase), the deficient enzyme in Gaucher disease. The synthesis several new pyrrolidine analogues substituted at nitrogen or α‐carbon atom with alkyl chains different lengths suggested an interpretation data led discovery two GCase inhibitors...

The ability to control cell alignment represents a fundamental requirement toward the production of tissue in vitro but also create biohybrid materials presenting functional properties human organs. However, cultures on standard commercial supports do not provide selective organization morphology, and different techniques, such as use patterned or stimulated substrates, are developed induce cellular alignment. In this work, new approach muscular morphogenesis is presented exploiting liquid...

Intrinsically disordered proteins (IDPs) are highly flexible molecules often linked to the onset of incurable diseases. Despite their great therapeutic potential, IDPs considered as undruggable because they lack defined binding pockets, which constitute basis drug discovery approaches. However, small that interact with intrinsically state α-synuclein, protein Parkinson's disease (PD), were recently identified and shown act chemical chaperones. Glucocerebrosidase (GCase) is an enzyme...

The oxidation of imines may give several products, such as oxaziridines, nitrones, amides, and other rearranged compounds. Therefore, its selectivity is a challenge that various methods have to face. controversial the using urea hydrogen peroxide (UHP) catalyzed by methyltrioxorhenium (MTO) addressed varying solvent, temperature, reaction time, amount oxidant, catalyst used. reactivity proved be particularly sensitive type solvent. use methanol furnished corresponding nitrones exclusive...

Abstract A D ‐mannose‐derived aldehyde with the ‐ lyxo configuration is a versatile key intermediate to functionally and stereochemically diversified piperidines. It allowed synthesis of natural 3,4,5‐trihydroxypiperidines new analogs through double reductive amination strategy novel 2‐cyanotrihydroxypiperidines highly regio‐ diastereoselective Strecker reaction.

Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable effects towards jack bean α-mannosidase and Golgi from Drosophila melanogaster, as well good selectivity with respect to lysosomal α-mannosidase, which is important for anticancer applications. STD NMR molecular modeling studies supported mechanism specific interactions of the bioactive iminosugars Jack α-mannosidase. TEM suggested binding mode that involves formation aggregates, result...

Abstract A general strategy for the synthesis of diversely substituted 3,4,5‐trihydroxypiperidines (including two natural products), 5‐amino‐3,4‐dihydroxypiperidines, 3,4,5‐trihydroxypipecolic acids, and 2‐(aminomethyl)‐3,4,5‐trihydroxypiperidines is reported. The procedure used a double reductive amination or Strecker reaction, starting from differently protected aldehydes readily synthesized on gram scale D ‐mannose. biological activities target compounds were evaluated, some them showed...

Gaucher disease (GD) is a rare genetic metabolic disorder characterized by dysfunction of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) due to mutations in gene GBA1, leading cellular accumulation glucosylceramide (GlcCer). While most current research focuses on primary accumulated material, lesser attention has been paid secondary storage materials and their reciprocal intertwining. By using novel approach based flow cytometry fluorescent labelling, we monitored changes...

Pharmacological chaperones (PCs) are small molecules that bind and stabilize enzymes. They can rescue the enzymatic activity of misfolded or deficient enzymes when they used at subinhibitory concentration, thus with minimal side effects. Chaperone Therapy (PCT) is an emerging treatment for many lysosomal storage disorders (LSDs) including Gaucher disease, most common, which characterized by a deficiency in GCase enzyme. We report herein straightforward synthetic strategy to afford C-2...

Gold glyconanoparticles (Au GNPs) decorated with the natural iminosugar DAB-1 at different densities are reported.

The reductive amination (RA) reaction plays a pivotal role in the synthesis of new C–N bonds, due to availability many different and low‐cost reagents their operational simplicity. introduction compound nitrogen‐containing moiety that can be reduced an amine medium allows perform cascade reactions which further expand this method. application intramolecular version RA carbohydrates polyhydroxypiperidine iminosugars, are among most challenging fascinating glycomimetics for synthetic chemist....

Towards human GCase activity enhancement by means of light responsive inhibitors.

The synthesis of five new multivalent derivatives a trihydroxypiperidine iminosugar was accomplished through copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction an azido ending piperidine and several propargylated scaffolds. resulting architectures were assayed as inhibitors lysosomal GCase, the defective enzyme in Gaucher disease. compounds resulted much more potent than parent monovalent reference compound, thus showing good effect. Biological investigation these pharmacological...

Abstract A remarkable enhancer of human glucocerebrosidase enzyme (GCase) was identified among a set dihydroazulene‐tagged iminosugars. An unprecedented 3.9‐fold increase in GCase activity detected on fibroblasts bearing the homozygous L444P mutation, which is frequently associated with neuronopathic Gaucher forms, and commonly results refractory to chaperone‐induced refolding.

New targets sensitive to multivalency: synthesis of nonavalent pyrrolidine iminosugars.

Piperidine-based photoswitchable derivatives have been developed as putative pharmacological chaperones for glucocerebrosidase (GCase), the defective enzyme in Gaucher disease (GD). The structure-activity study revealed that both iminosugar and light-sensitive azobenzene are essential features to exert inhibitory activity towards human GCase a system with correct inhibition trend (IC50 of light-activated form lower than IC50 dark form) was identified. Kinetic analyses showed all compounds...

Gaucher disease is caused by mutations in human acid β-glucosidase or glucocerebrosidase (GCase), the enzyme responsible for hydrolysis of glucosyl ceramide lysosomes. Imino- and azasugars such as 1-deoxynojirimycin isofagomine are strong inhibitors interest pharmacological chaperone therapy disease. Despite several crystal structures with imino- bound active site having been resolved, actual acid-base chemistry binding not known. In this study we show, using photoinduced electron transfer...