16281-39-3Relevant academic research and scientific papers
Click Chemistry-Assisted Bioconjugates for Hapten Immunodiagnostics
López-Puertollano, Daniel,Agulló, Consuelo,Mercader, Josep V.,Abad-Somovilla, Antonio,Abad-Fuentes, Antonio
, p. 956 - 964 (2020)
Bioorthogonal reactions have revolutionized the way low-molecular-weight compounds are coupled to biomolecules. Organic chemistry, polymer science, and chemical biology are among the disciplines that have benefited the most from this breakthrough. Despite the reliability of the click chemistry concept for the efficient and chemoselective functionalization of biomacromolecules with haptens at preferred positions, the fact that azide-alkyne cycloaddition reactions originate new chemical moieties as part of the linker may have delayed their application in the immunodiagnostic field. Using the mycotoxin ochratoxin A as a model compound, we herein demonstrate for the first time that bioconjugates arising from the ligation between an azido-bearing hapten and an alkyne-modified carrier protein are able to elicit the generation of high-affinity monoclonal antibodies suitable for the development of rapid methods for the immunodetection of small organic molecules.
First synthesis of a stable isotope of Ochratoxin A metabolite for a reliable detoxification monitoring
Bouisseau, Anais,Roland, Aurelie,Reillon, Florence,Schneider, Remi,Cavelier, Florine
, p. 3888 - 3890 (2013/09/02)
Due to its toxicity and presence in numerous food products, Ochratoxin A (OTA) has drawn attention for decades. This article summarizes the first synthesis of a labeled analogue of Ochratoxin α (OTα), one of the main products generated by the metabolization of OTA by microorganisms. This synthesis also led to a new labeled analogue of OTA with the deuteration located on the dihydroisocoumarin moiety allowing thus both the accurate quantification of OTA and OTα and the establishing of a reliable detoxification rate.
Total synthesis and cytotoxicity evaluation of all ochratoxin A stereoisomers
Cramer, Benedikt,Harrer, Henning,Nakamura, Kazuhiko,Uemura, Daisuke,Humpf, Hans-Ulrich
experimental part, p. 343 - 347 (2010/04/05)
The mycotoxin ochratoxin A is a potent inhibitor of the protein biosynthesis and known to be cytotoxic in nanomolar concentrations. In order to investigate the relationship between stereochemistry and cytotoxicity of this compound, all four ochratoxin A stereoisomers have been synthesized. Using the liver cell line Hep G2, the compounds were tested for cytotoxic and apoptotic potential. It could be shown, that the l-configuration of the phenylalanine moiety of the molecule is mostly responsible for the high cytotoxicity of ochratoxin A while the stereocenter at the dihydroisocoumarine structure is of less importance.
A new and expedient total synthesis of ochratoxin A and d 5-ochratoxin A
Gabriele, Bartolo,Attya, Mohamed,Fazio, Alessia,Di Donna, Leonardo,Plastina, Pierluigi,Sindona, Giovanni
body text, p. 1815 - 1820 (2010/02/28)
A new total synthesis of the mycotoxin ochratoxin A (OTA) is presented, in which it is prepared in 9% overall yield from commercially available substrates. The key step consists of the condensation reaction between protected L-phenylalanine and 5-chloro-8-hydroxy-3-methyl-1-oxoisochromane-7-carboxylic acid (ochratoxin α, OTα). The same strategy could be successfully applied to L-d5-phenylalanine, leading to the first total synthesis of d5-OTA, a molecular tracer for the detection and analytical quantification of the natural mycotoxin in food samples by means of stable isotope dilution assay (SIDA). Georg Thieme Verlag Stuttgart.
Mise au point. Reaction de metallation ortho dirigee des composes aromatiques. Nouvelles methodologies et applications en synthese organique
Snieckus, Victor
, p. 67 - 78 (2007/10/02)
In recent years, the aromatic directed metalation reaction has developed into a broadly useful protocol for the regiospecific construction of polysubstituted aromatics and has been applied in efficient total syntheses of diverse classes of natural products.In this review, both methodological and total synthesis advences using primarily the tertiary carboxamide and carbamate as metalation directors are presented.First, general aspects such as the nature of the directed metalation group (DMG) (scheme 1), the effect of two meta-related DMGs on the metalation process (scheme 2), the relative directed metalation abilities of different DMGs (scheme 3), and the scope of reaction with various electrophiles (scheme 4) are first discussed.Next, the advantage of the directed metalation tactic for the synthesis of several classes of natural products (anthramycin, scheme 7 ; angular anthracyclinones, scheme 8 ; and cannabifuran, schemes 10 and 11) are conceptualized and briefly described.Further, the significance of silicon functionality in context of directed metalation chemistry is demonstrated by its use for protection of prefferentially reactive aromatic C-H and C-methyl sites (scheme 12), ipso desilylation (scheme 13), generation of o-quinodimethanes (scheme 14), and overcoming normal Friedel-Crafts regioselectivity in carboannelation (schemes 16-18).Aspects of the tertiary carbamate as a ortho metalation director (scheme 19) are delineated : the development of an anionic ortho-Fries rearrangement (scheme 21) ; a new, also anionic, ortho-tolyl carbamate rearrangement leading to benzofuranones (scheme 22) ; its comparison with tertiary amide a methoxymethoxy as a DMG (scheme 23) ; its use for the generation of benzamide benzyne intermediates (scheme 24) ; metalation of O-pyridyl carbamates (scheme 25) and its synthetic ramifications (schemes 26-28) ; and its application in conjunction with amide metalation for the synthesis of the ochratoxin metaolites (scheme 29).Dimetalation of benzamides (scheme 32), phthalamides (scheme 33), p,p- and o,o-aryl dicarbamates (schemes 34 and 35) are supported by reactions with various electrophiles.To conclude, recent work aimed at connecting the aromatic directed metalation strategy to other modern synthetic methods is described.Coupling the directed metalation process with the radical-induced annelation provides new routes to benzofurans (scheme 36) and furopyridines (scheme 37) and is applied to the preparation of a key synthon for the mould metabolite, aflatoxin (scheme 38).Anionic aromatic and heteroaromatic ring annelation processes which depend upon ortho metalated precursors lead to naphthalene (schemes 39-41) and 4-quinolone (scheme 42) derivatives.Aryl boronic acids with ortho-DMGs, synthesized by metalation-boronation and ipso borodesilylation methods, are cross coupled with aryl bromides under palladium (O) catalysis leading to new routes for the preparation of unsymmetrical biaryls (scheme 45).
Synthesis of ochratoxins
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, (2008/06/13)
A simple, direct synthesis route is provided for Ochratoxin compounds, particularly Ochratoxin A, Ochratoxin B, and Ochratoxin C. The reaction involves treating the dimethyl ester of 2-hydroxy-4-methylbenzene-1,3-dioic acid with a deprotonating agent, followed by addition of acetaldehyde, to provide a precursor compound, which can conveniently be converted to Ochratoxins A, B or C. The synthesis route allows for the first time laboratory and industrial scale synthesis of ochratoxins A, B and C in large quantities and pure form making them available as toxins, for use as anti-toxin investigation works, and for biological activity investigations and residue studies.
