Papers by Claude COMMANDEUR
Cancer Research, 2018
Adenosine is the key immunometabolite responsible for immune tolerance in tumors. It is present i... more Adenosine is the key immunometabolite responsible for immune tolerance in tumors. It is present in normal tissue in low concentrations, having various physiological functions. In the tumor, its concentration increases rapidly, as a result of overexpression of enzymes producing adenosine, additionally enhanced by hypoxia and inflammation. Adenosine inhibits the biological functions of T lymphocytes infiltrating the cancer tissue by binding to the A2A receptor. The affinity to A2B receptor is believed to attenuate the response of dendritic cells and other parts of innate system. Thus blocking simultaneously the effects mediated by both receptor subtypes with dual inhibitor seems to be a viable approach to a single agent cancer immunotherapy or a combination with current immunotherapeutic agents. We have discovered a novel series of potent and selective A2A/A2B inhibitors. Best compounds present subnanomolar activity in both in vitro recombinant cellular model and in primary human cell...
Bioorganic & Medicinal Chemistry Letters, 2018
Molecular Cancer Therapeutics, 2015
Breast cancer is the second most common cancer in the world and the most frequent cancer among wo... more Breast cancer is the second most common cancer in the world and the most frequent cancer among women. Despite the progress in developing breast cancer therapies, approximately, 15% of all breast cancers are diagnosed as triple negative breast cancer (TNBC) and due to the lack of estrogen and progesterone receptors this subgroup of patients remains difficult to treat with hormonal therapies. Additionally, therapies targeting HER2, such as Herceptin, are also inefficient against TNBC. In recent years, maternal embryonic leucine zipper kinase (MELK) has been identified as a novel oncogenic target that is highly expressed in several types of solid cancers: breast (especially triple negative breast cancer), colon, ovary, lung, and brain and present at low levels in normal tissues. MELK overexpression in patient tumors strongly correlates with poor prognosis in glioblastoma and breast cancer. siRNA mediated knockdown of MELK kinase significantly inhibits growth of tumor cell lines both in...
Tetrahedron Letters, 2009
ABSTRACT A highly effective procedure is reported to synthesize a substituted bicyclo[4.2.0]octen... more ABSTRACT A highly effective procedure is reported to synthesize a substituted bicyclo[4.2.0]octenol derivative by regioselective cycloaddition of phenyl-1-propynyl sulfide with cyclohexenone followed by selective reduction of the ketone group and reductive elimination of phenylsulfonyl group. The strained cyclobutene ring was then engaged in a ring-opening/cross metathesis sequence in the presence of Hoveyda–Grubbs 2nd generation catalyst. The synthesis serves as a model study toward the synthesis of the sesquiterpene diol portion of the terpenoid pyrrolobenzoxazine alkaloids, CJ-12662 and CJ-12663.
Tetrahedron, 2011
This report describes a detailed study of the oxidation-Meisenheimer rearrangement of N-methyl-3h... more This report describes a detailed study of the oxidation-Meisenheimer rearrangement of N-methyl-3hydroxy-7-chloropyrroloindoline ethyl ester and the corresponding O-Boc and N-Boc derivatives. Experimental conditions were found, which allowed the selective Boc protection of either the tertiary alcohol substituent or the NH group of the aminal function. It was shown that both the parent compound and its O-Boc derivative yielded a mixture of oxazines and, in some cases, N-oxides upon treatment with m-CPBA. MS fragmentation (APCI) clearly differentiates formation of N-oxides and oxazines. The N-Boc derivatives exclusively yielded the N-oxides showing that the Meisenheimer rearrangement requires the presence of a high energy lone pair on the neighbouring nitrogen atom. Both the parent compound and the O-Boc derivative gave a mixture of rearranged products and N-oxide depending on the reaction conditions.
Journal of Organometallic Chemistry, 2003
... The palladium-catalyzed allylation of nucleophiles (Tsuji-Trost reaction) is a useful synthet... more ... The palladium-catalyzed allylation of nucleophiles (Tsuji-Trost reaction) is a useful synthetic method due to its broad scope, facile operation, and stereochemical outcome since many nucleophiles react with overall retention of configuration at the electrophile [1]. Attack of a ...
The Journal of Organic Chemistry, 2003
European Journal of Organic Chemistry, 2003
A new palladium-catalysed allylic alkylation affording silylated 3-vinylpyrrolidones has been dev... more A new palladium-catalysed allylic alkylation affording silylated 3-vinylpyrrolidones has been developed. The method relies upon the interaction between a stabilized acetamide enolate anion and a silicon-containing, nitrogen-tethered η3-allylpalladium moiety. Two variants have been studied, involving the location of the silicon atom on either olefinic carbon atom of the cyclisation precursor. In both cases 5-exo ring closure was the only cyclisation process observed. The stereoselectivity of these processes is discussed. These results contrast with related β-oxo ester cyclisations, in which competitive 7-endo mode is observed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
European Journal of Organic Chemistry, 2007
In order to obtain functionalized naphthoquinones, a systematic study of the Kochi-Anderson proce... more In order to obtain functionalized naphthoquinones, a systematic study of the Kochi-Anderson procedure for the alkylation of quinones is presented. While linear amino acids of different lengths were good substrates for this decarboxylation procedure, chiral α-amino acids were unsuccessful substrates. The best reaction conditions were evaluated with βalanine and then applied to a series of carboxylic acids to obtain chemical diversity on the naphthoquinones. We ob-[a] UMR 5248 CBMN,
La métathèse d’oléfines est une réaction qui a été observée dès les années 1950 par un pétrochimi... more La métathèse d’oléfines est une réaction qui a été observée dès les années 1950 par un pétrochimiste de chez DuPont, H.S. Eleuterio [1] [2] [3]. Ce chimiste avait observé la transformation d’une oléfine cyclique en polymère insaturé en présence d’un catalyseur métallique, mais il n’avait pas pris conscience de l’importance de cette réaction. En revanche, en 1964, R.L. Banks et G.C. Bailey de la Phillips Petroleum ont vu l’impact que pouvait avoir la métathèse des oléfines car ils avaient pu transformer le propylène en éthylène et en butène par chauffage, grâce à la présence d’un catalyseur au molybdène [4]. La même année, G. Natta, qui appartenait à l’Institut de recherche industrielle de Milan , avait constaté qu’en laissant une oléfine cyclique en présence de métaux tels que le tungstène ou le molybdène, il pouvait obtenir un polymère insaturé de masse élevée possédant des doubles liaisons [5] et, en 1967, N. Calderon, un chimiste appartenant à la Good Year Tire&Rubbers, montra qu...
Accounts of Chemical Research, 2015
A myriad of natural and/or biologically active products include nitrogen- and oxygen-containing s... more A myriad of natural and/or biologically active products include nitrogen- and oxygen-containing saturated heterocycles, which are thus considered as attractive scaffolds in the drug discovery process. As a consequence, a wide range of reactions has been developed for the construction of these frameworks, much effort being specially devoted to the formation of substituted tetrahydropyrans and piperidines. Among the existing methods to form these heterocycles, the metal-catalyzed heterocyclization of amino- or hydroxy-allylic alcohol derivatives has emerged as a powerful and stereoselective strategy that is particularly interesting in terms of both atom-economy and ecocompatibility. For a long time, palladium catalysts have widely dominated this area either in Tsuji-Trost reactions [Pd(0)] or in an electrophilic activation process [Pd(II)]. More recently, gold-catalyzed formation of saturated N- and O-heterocycles has received growing attention because it generally exhibits high efficiency and diastereoselectivity. Despite their demonstrated utility, Pd- and Au-complexes suffer from high costs, toxicity, and limited natural abundance, which can be barriers to their widespread use in industrial processes. Thus, the replacement of precious metals with less expensive and more environmentally benign catalysts has become a challenging issue for organic chemists. In 2010, our group took advantage of the ability of the low-toxicity and inexpensive FeCl3 in activating allylic or benzylic alcohols to develop iron-catalyzed N- and O-heterocylizations. We first focused on N-heterocycles, and a variety of 2,6-disubstituted piperidines as well as pyrrolidines were synthesized in a highly diastereoselective fashion in favor of the cis-compounds. The reaction was further extended to the construction of substituted tetrahydropyrans. Besides triggering the formation of heterocycles, the iron salts were shown to induce a thermodynamic epimerization, which is the key to reach the high diastereoselectivities observed in favor of the most stable cis-isomers. It is worth noting that spiroketals could be prepared by using this method, which was successfully applied to a synthetic approach toward natural products belonging to the bistramide family. We then turned our attention to heterocycles incorporating two heteroatoms such as isoxazolidines. These frameworks can be found in biologically active natural products, and in addition, they can be transformed into 1,3-amino alcohols, which are of importance in organic chemistry. The use of FeCl3·6H2O allowed the access to a large variety of 3,5-disubstituted isoxazolidines from δ-hydroxylamino allylic alcohol derivatives with good yields and diastereoselectivities in favor of the cis-isomer. Recently, a Lewis acid-catalyzed synthesis of six- and five-membered ring carbonates starting from linear tert-butyl carbonates was reported. In some cases, the mild and chemoselective InCl3 was preferred over FeCl3·6H2O to avoid side-product formation. The resulting cyclic carbonates were easily transformed into 1,3- or 1,2-diols, and a total synthesis of (3S,5S)-alpinikatin was achieved.
Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, 2013
ABSTRACT Carbonylations of olefins, acetylenes, halides, alcohols, amines, nitro compounds, etc.,... more ABSTRACT Carbonylations of olefins, acetylenes, halides, alcohols, amines, nitro compounds, etc., promoted by transition metal complexes are very important in both industrial and laboratory organic syntheses. The mechanisms of those reactions have been studied extensively, especially for those associated with commercial processes. The research on the utilization of carbon monoxide was substantially promoted by the ‘‘C1 Chemistry’’ projects with regard to the establishment of chemical technology, which enables us to produce gasoline, ethylene glycol, acetic acid, ethanol, methanol, etc., directly from carbon monoxide and hydrogen in the presence of appropriate catalysts. The use of carbon monoxide as ‘‘one-carbon unit’’ has a high potential in modern organic synthesis as well. Accordingly, a variety of new carbonylations have been explored, which may eventually become commercial processes. This chapter covers the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions from 1993 to early 2005. In addition, technical development in carbonylation processes with the use of microwave irradiation as well as new reaction media such as supercritical carbon dioxide and ionic liquids are also discussed. These carbonylation reactions provide efficient and powerful methods for the syntheses of a variety of carbonyl compounds, amino acids, heterocycles, and carbocycles.
Tetrahedron, 2012
ABSTRACT In continuance of our search for newer anti-cancer agents we were interested on embelin,... more ABSTRACT In continuance of our search for newer anti-cancer agents we were interested on embelin, a XIAP (Xlinked inhibitor of apoptosis protein) inhibitor. This natural benzoquinone bear a lipophilic chain and we report here the synthesis of hydrophilic analogues of embelin. To allow a large flexibility in the nature of the hydrophilic group, three amines with different length of carbon chain bearing a protected benzoquinone were prepared. The cytotoxic effects of these derivatives were evaluated on KB cell line.
Pure and Applied Chemistry, 2000
ABSTRACT An advanced spiroketal intermediate toward the synthesis of 39-oxobistramide K was prepa... more ABSTRACT An advanced spiroketal intermediate toward the synthesis of 39-oxobistramide K was prepared, fragment C14–C40. This fragment was obtained in 19 steps with an overall yield of 6.2 % using a FeCl3-catalyzed spiroketalization as the key step.
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Papers by Claude COMMANDEUR