Showing papers by "Christian V. Stevens published in 2008"
238 citations
TL;DR: The aim of this study is to predict, synthesize and apply in vivo molecules with an optimal anti-invasive, and hence an anti-metastatic activity against cancer.
Abstract: Because invasion is, either directly or via metastasis formation, the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. We have established a screening program for potentially anti-invasive compounds. The assay is based on organotypic confronting cultures between human invasive cancer cells and a fragment of normal tissue in three dimensions. Anti-invasive agents appeared to be heterogeneous with regard to their chemical nature, but plant alkaloids, polyphenolics and some of their synthetic congeners were well represented. Even within this group, active compounds were quite diverse: (+)-catechin, tangeretin, xanthohumol and other prenylated chalcones, 3,7-dimethoxyflavone, a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin. The data gathered in this system are now applied in two projects. Firstly, structure-activity relationships are explored with computer models using an artificial neural network approach, based on quantitative structural descriptors. The aim of this study is the prediction and design of optimally efficient anti-invasive compounds. Secondly, the metabolism of orally ingested plant polyphenolics by colonic bacteria is studied in a simulator of the human intestinal microbial ecosystem (SHIME) and in human intervention trials. This method should provide information on the final bioavailability of the active compounds in the human body, with regard to microbial metabolism, and the feasibility of designing pre- or probiotics that increase the generation of active principles for absorption in the gastro-intestinal tract. The final and global aim of all these studies is to predict, synthesize and apply in vivo molecules with an optimal anti-invasive, and hence an anti-metastatic activity against cancer.
38 citations
TL;DR: A key intermediate for the synthesis of Tyromycin A, a C-20 tetrachlorodicarboxylic acid, was produced in six steps starting with the dimerization of methyl 10-undecenoate which was obtained from a renewable resource, e.g. castor oil.
Abstract: A key intermediate for the synthesis of Tyromycin A, a C-20 tetrachlorodicarboxylic acid, was produced in six steps starting with the dimerization of methyl 10-undecenoate which was obtained from a renewable resource, e.g. castor oil. The acyloin condensation product was then oxidized, transformed to the diene, followed by ozonization, chlorination and finally oxidation to the corresponding tetrachlorodicarboxylic acid.
21 citations
TL;DR: An RCM strategy for the synthesis of phosphonylated benzazocines and their corresponding isomerised analogues was developed in this article, where aminophosphonate precursors were obtained by a one-pot three-component condensation in moderate yield.
18 citations
TL;DR: In this article, the NHC-based catalysts were found to be more efficient in the polymerization of trans,trans,trans-1,5,9-cyclododecatriene to obtain 1,4 polybutadiene.
15 citations
TL;DR: In this article, 1,1-Bisphosphono-2-aza-1,3-dienes are formed by 1,4-dehydrohalogenation of the corresponding N-(bisphosphonomethyl)-α-haloimines in moderate to good yields.
14 citations
TL;DR: In this paper, a ring closure method was proposed to form 1H-isochromeno[3,4-d]imidazol-5-ones via ring closure starting from 3-amino-4-(arylamino)-1H-Isochromen-1-ones.
12 citations
TL;DR: Density functional theory methods and several high-level post Hartree-Fock procedures were used to rationalize the observed isomer ratio of the IMDAF-reactions, and a thermodynamic preference for the product with the phosphonate function in the endo position was observed experimentally and was confirmed theoretically.
Abstract: During the synthesis of tricyclic phosphonopyrrolidines via intramolecular Diels−Alder reactions of 1-acylamino(furan-2-yl)methyl phosphonates, two isomers are formed in most cases. The presence of a short three-atom tether together with spectroscopic data, including difference NOE, revealed that the cycloaddition occurred exo, but the phosphonate substituent on the tether had an exo or endo orientation. This was confirmed via X-ray analysis. A thermodynamic preference for the product with the phosphonate function in the endo position was observed experimentally and was confirmed theoretically. Density functional theory methods and several high-level post Hartree−Fock procedures were used to rationalize the observed isomer ratio of the IMDAF-reactions. This was done for two different types of reagents: with the activating carbonyl group in the tether or as a substituent on the tether. For the first type of molecules there is a large steric hindrance of the bulky tether substituents that disfavors the exo-...
11 citations
TL;DR: In this article, a straightforward ring transformation giving polymethylenebis(hydantoins) was extended, as these are HMBA analogues, and it was established by HSQC experiments with inverse detection that only the E isomers were formed in the cases of the 24 and 26-membered heterocycles.
9 citations
25 Feb 2008
6 citations
Patent•
08 Aug 2008
TL;DR: A group of substituted 7-azabicyclo-[2.2.1]heptyl derivatives with biological activity was described in this paper, and a synthetic method for producing such derivatives was proposed.
Abstract: The present invention relates to a group of substituted-7-azabicyclo--[2.2.1]heptyl derivatives with biological activity. The present invention also relates to synthetic methods for producing said substituted-7-azabicyclo--[2 2.1]heptyl derivatives. The present invention also relates to certain intermediates for producing such substituted-7-azabicyclo-[2 2.1]heptyl derivatives, as well as a synthetic method for producing such intermediates. The present invention also relates to pharmaceutical compositions comprising such substituted-7-azabicyclo-[2.2.1]heptyl deriva-tives, as well as their use as medicaments for the treatment of diseases mediated by a Nicotinic Acetylcholine Receptor or a receptor being a member of the Neurotransmitter--gated Ion Channel Superfamily, such as pain, Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy and nicotine addiction.
Patent•
08 Aug 2008TL;DR: In this paper, a group of substituted 7-azabicyclo-[2.2.1]heptyl derivatives with biological activity was presented, which were used as medicaments for the treatment of diseases mediated by a Nicotinic Acetylcholine Receptor or a receptor being a member of the Neurotransmitter-gated Ion Channel Superfamily.
Abstract: The present invention relates to a group of substituted-7-azabicyclo-[2.2.1]heptyl derivatives with biological activity. The present invention also relates to synthetic methods for producing said substituted-7-azabicyclo-[2.2.1]heptyl derivatives. The present invention also relates to certain intermediates for producing such substituted-7-azabicyclo-[2.2.1]heptyl derivatives, as well as a synthetic method for producing such intermediates. The present invention also relates to pharmaceutical compositions comprising such substituted-7-azabicyclo-[2.2.1]heptyl derivatives, as well as their use as medicaments for the treatment of diseases mediated by a Nicotinic Acetylcholine Receptor or a receptor being a member of the Neurotransmitter-gated Ion Channel Superfamily, such as pain, Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy and nicotine addiction.
TL;DR: The 1,4 and 1,2-addition of phosphites to α,β-unsaturated hydrazones was investigated in this article, which yielded 3-phosphonyl-1-hydrazinoalkyl phosphonates.
Abstract: The 1,4- and 1,2-addition of phosphites to α,β-unsaturated hydrazones was investigated. When silylated phosphites and trialkyl phosphites were compared, trialkyl phosphites gave better conversions and subsequently higher yields. A variety of hydrazones were evaluated as substrate in this reaction, which yield 3-phosphonyl-1-hydrazinoalkyl phosphonates.
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TL;DR: In this article, 1,1-Bisphosphono-2-aza-1,3-dienes are formed by 1,4-dehydrohalogenation of the corresponding N-(bisphosphonomethyl)-α-haloimines in moderate to good yields.
Abstract: 1,1-Bisphosphono-2-aza-1,3-dienes are formed by 1,4-dehydrohalogenation of the corresponding N-(bisphosphonomethyl)-α-haloimines in moderate to good yields. The precursors could be formed by condensation of bisphosphono-amines and the corresponding α-haloaldehydes.
TL;DR: In this paper, the synthesis of benzospiro-indolizidinepyrrolidinones is described by a domino atom transfer radical cyclization reaction using a copper catalyst.
Abstract: In this Letter the synthesis of benzospiro-indolizidinepyrrolidinones is described by a domino atom transfer radical cyclization reaction using a copper catalyst. The structure of one of the products was established by single crystal X-ray diffraction. The investigated precursors, bearing a homo allyl substituent on the N -indole, result in a 5- exo - trig , followed by a 6- endo - trig cyclization. When the N -indole is substituted with an allyl group, only the spiro-cyclization occurs.