41242-94-8Relevant academic research and scientific papers
Studies on the formation of methylglyoxal from dihydroxyacetone in Manuka (Leptospermum scoparium) honey
Atrott, Julia,Haberlau, Steffi,Henle, Thomas
, p. 7 - 11 (2012)
Dihydroxyacetone (DHA) and methylglyoxal (MGO) are unique carbohydrate metabolites of manuka honey. A method for the reliable quantification of DHA in honey samples was established, based on derivatization with o-phenylenediamine (OPD) and subsequent RP-HPLC with UV detection. The previously unknown reaction product of DHA and OPD was identified as 2-hydroxymethylquinoxaline by spectroscopic means. DHA was exclusively determined in 6 fresh manuka honeys originating directly from the beehive as well as 18 commercial manuka honey samples, ranging from 600 to 2700 mg/kg and 130 to 1600 mg/kg, respectively. The corresponding MGO contents varied from 50 to 250 mg/kg in fresh and 70 to 700 mg/kg in commercial manuka honey samples. A good linear correlation between DHA and MGO values in commercial manuka honeys was observed, resulting in a mean ratio of DHA to MGO of 2:1. In contrast to this, the DHA-to-MGO relation was much higher in fresh manuka honeys but approximated to a ratio of 2:1 while honey ripening. Heating experiments revealed that MGO formation based on thermal treatment as a consequence, for example, of caramelization in honey does not occur. DHA and MGO can serve as suitable unique quality parameter for manuka honey.
Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
Aleku, Godwin A.,Leys, David,Roberts, George W.
, p. 3927 - 3939 (2020/07/09)
We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
Discovery of potent and specific dihydroisoxazole inhibitors of human transglutaminase 2
Kl?ck, Cornelius,Herrera, Zachary,Albertelli, Megan,Khosla, Chaitan
supporting information, p. 9042 - 9064 (2015/03/14)
Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes the posttranslational modification of glutamine residues on protein or peptide substrates. A growing body of literature has implicated aberrantly regulated activity of TG2 in the pathogenesis of various human inflammatory, fibrotic, and other diseases. Taken together with the fact that TG2 knockout mice are developmentally and reproductively normal, there is growing interest in the potential use of TG2 inhibitors in the treatment of these conditions. Targeted-covalent inhibitors based on the weakly electrophilic 3-bromo-4,5-dihydroisoxazole (DHI) scaffold have been widely used to study TG2 biology and are well tolerated in vivo, but these compounds have only modest potency, and their selectivity toward other transglutaminase homologues is largely unknown. In the present work, we first profiled the selectivity of existing inhibitors against the most pertinent TG isoforms (TG1, TG3, and FXIIIa). Significant cross-reactivity of these small molecules with TG1 was observed. Structure-activity and -selectivity analyses led to the identification of modifications that improved potency and isoform selectivity. Preliminary pharmacokinetic analysis of the most promising analogues was also undertaken. Our new data provides a clear basis for the rational selection of dihydroisoxazole inhibitors as tools for in vivo biological investigation.
Gold catalysis opens up a new route for the synthesis of benzimidazoylquinoxaline derivatives from biomass-derived products (glycerol)
Climent, Maria J.,Corma, Avelino,Iborra, Sara,Martinez-Silvestre, Sergio
, p. 3866 - 3874 (2014/01/06)
Process intensification by using well-defined solid catalysts able to perform one-pot multistep reactions is one of the open fronts in heterogeneous catalysis. This is even more relevant if new, more efficient synthesis routes are open. Herein, a gold catalyst was used to synthesize benzimidazoylquinoxalines compounds by two efficient and selective novel methods in a multistep one-pot methodology. The first method involved the synthesis of benzimidazoylquinoxaline compounds with the same substituents in both heterocycles through oxidation-cyclization of glycerol with o-phenylenediamine derivatives, whereas the second one allowed the synthesis of benzimidazoylquinoxalines compounds with different substituents in each aromatic ring through coupling of o-phenylenediamine derivatives with glyceraldehyde in a first stage to produce the benzimidazol compound as an intermediate, followed by an oxidation-cyclization with another o-phenylenediamine compound in a second stage. Both stages were performed by using gold nanoparticles supported on nanoparticulated ceria (Au/CeO2) as the catalyst and air as the oxidant, in absence of any homogeneous reagent. A reaction mechanism has been proposed. A smooth route: Benzimidazoylquinoxaline derivatives can be obtained in good yields through one-pot oxidative coupling of glycerol or glyceraldehydes with 1,2-phenylenediamines in a two-step reaction, using Au/CeO2 as the catalyst, base-free conditions, mild temperature, and air as the oxidant. Copyright
Hydroxymethylations of aryl halides by Pd-catalyzed cross-couplings with (benzoyloxy)methylzinc iodide - Scope and limitations of the reaction
Hasník, Zbyněk,?ilhár, Peter,Hocek, Michal
, p. 543 - 546 (2008/12/22)
Palladium-catalyzed cross-coupling reactions of (benzoyloxymethyl)zinc iodide with diverse (het)aryl halides leading to (benzoyloxymethyl)(het)arenes were studied to define the scope of this reaction. It has been found that this reaction is only applicable for electron-deficient aryl halides and the most efficient it is for 2-halopyridines and 4-halopyrimidines. Deprotection of the intermediates gives (hydroxymethyl)pyridines and -pyrimidines in high yields. Georg Thieme Verlag Stuttgart.
Substituted 4-aryl-4h-pyrrolo[2,3-h]chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof
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Page/Page column 17, (2008/06/13)
The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the Formula (I): wherein R1, R3-R5, A, D, Y and Z are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
Intercalator amino acids: Synthesis of heteroaryl alanines
Krippner,Harding
, p. 1793 - 1804 (2007/10/02)
Stereoselective alkylation of (S)-(-)-2-t-butyl-1-t-butyloxycarbonyl-3-methyl-4-imidazolinone with 2-chloromethylquinoline, 2-chloromethylquinoxaline and 5-chloromethyl-1,10-phenanthroline, followed by hydrolysis, afforded the corresponding (S)-(+)-α-amino acids with high enantiomeric excess.
