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Crich D.,CNRS Natural Product Chemistry Institute
Accounts of Chemical Research | Year: 2010

Glycosylation is arguably the most important reaction in the field of glycochemistry, yet it involves one of the most empirically interpreted mechanisms in the science of organic chemistry. The β-mannopyranosides, long considered one of the more difficult classes of glycosidic bond to prepare, were no exception to this rule. A number of logical but circuitous routes for their preparation were described in the literature, but they were accompanied by an even greater number of mostly ineffective recipes with which to access them directly. This situation changed in 1996 with the discovery of the 4,6-O-benzylidene acetal as a control element permitting direct entry into the β-mannopyranosides, typically with high yield and selectivity. The unexpected nature of this phenomenon demanded study of the mechanism, leading first to the demonstration of the α-mannopyranosyl triflates as reaction intermediates and then to the development of α-deuterium kinetic isotope effect methods to probe their transformation into the product glycosides. In this Account, we assemble our observations into a comprehensive assessment consistent with a single mechanistic scheme. The realization that in the glucopyranose series the 4,6-O-benzylidene acetal is α-rather than β-directing led to further investigations of substituent effects on the stereoselectivity of these glycosylation reactions, culminating in their explanation in terms of the covalent α-glycosyl triflates acting as a reservoir for a series of transient contact and solvent-separated ion pairs. The function of the benzylidene acetal, as explained by Bols and co-workers, is to lock the C6-O6 bond antiperiplanar to the C5-O5 bond, thereby maximizing its electron-withdrawing effect, destabilizing the glycosyl oxocarbenium ion, and shifting the equilibria as far as possible toward the covalent triflate. β-Selective reactions result from attack of the nucleophile on the transient contact ion pair in which the α-face of the oxocarbenium ion is shielded by the triflate counterion. The α-products arise from attack either on the solvent-separated ion pair or on a free oxocarbenium ion, according to the dictates of the anomeric effect. Changes in selectivity from varying stereochemistry (glucose versus mannose) or from using different protecting groups can be explained by the shifting position of the key equilibria and, in particular, by the energy differences between the covalent triflate and the ion pairs. Of particular note is the importance of substitutents at the 3-position of the donor; an explanation is proposed that invokes their evolving torsional interaction with the substituent at C2 as the chair form of the covalent triflate moves toward the half-chair of the oxocarbenium ion. © 2010 American Chemical Society.

Desnous C.,CNRS Natural Product Chemistry Institute | Guillaume D.,French National Center for Scientific Research | Clivio P.,French National Center for Scientific Research
Chemical Reviews | Year: 2010

The unique photoreactivity of spore DNA was studied. Since spore photoproduct formation under the influence of UV-A and B can be in part prevented by spore outer layer components, spore photoproduct formation under UV-C radiation and its subsequent efficient repair also raises the question of rationale for the conservation of this process in some Bacillus species and also of the preservation of some of its associated molecules. It can be easily understood that a UV-C protective system was necessary for prokaryote survival when it was reaching the Earth's surface. Even if under sunlight SP DNA is formed in small amounts in bacterial spore DNA, such wavelengths lead to other photoproducts whose biological importance appears also critical and consequently whose repair is highly important for spore survival. SPDNA formation and repair could be viewed as a complex but seldom used protective pathway whose genetic information has been preserved.

Roulland E.,CNRS Natural Product Chemistry Institute
Angewandte Chemie - International Edition | Year: 2011

Meet the challenge! The time has come for organic chemists to devise more economically and ecologically sustainable strategies for multistep synthesis. One way to meet this challenge is to achieve protecting-group-free total synthesis. The recent progress accomplished in the field of catalyzed reactions will help chemists to meet this challenge (see figure; PG=protecting group). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rodriguez R.,CNRS Natural Product Chemistry Institute | Rodriguez R.,University Pierre and Marie Curie | Miller K.M.,University of Texas at Austin
Nature Reviews Genetics | Year: 2014

Small molecules-including various approved and novel cancer therapeutics-can operate at the genomic level by targeting the DNA and protein components of chromatin. Emerging evidence suggests that functional interactions between small molecules and the genome are non-stochastic and are influenced by a dynamic interplay between DNA sequences and chromatin states. The establishment of genome-wide maps of small-molecule targets using unbiased methodologies can help to characterize and exploit drug responses. In this Review, we discuss how high-throughput sequencing strategies, such as ChIP-seq (chromatin immunoprecipitation followed by sequencing) and Chem-seq (chemical affinity capture and massively parallel DNA sequencing), are enabling the comprehensive identification of small-molecule target sites throughout the genome, thereby providing insights into unanticipated drug effects.

Li J.,CNRS Natural Product Chemistry Institute | Neuville L.,CNRS Natural Product Chemistry Institute
Organic Letters | Year: 2013

An efficient copper-catalyzed synthesis of 1,2,4-trisubstituted imidazoles using amidines and terminal alkynes has been developed. Overall, the oxidative process, which involves Na2CO3, pyridine, a catalytic amount of CuCl2·2H2O, and oxygen (1 atm), consisted of a regioselective diamination of alkynes allowing the synthesis of diverse imidazoles in modest to good yields. © 2013 American Chemical Society.

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