- C-H functionalization logic enables synthesis of (+)-hongoquercin A and related compounds
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The specifics: A synthesis of the sesquiterpenoid antibiotic (+)-hongoquercin A using sequential site-specific C-H methylation and oxidation reactions is described. A key advancement toward this goal was the development of a ligand-accelerated C-H methylation reaction, and enabled the generation of a library of eight structurally diverse analogues. Copyright
- Rosen, Brandon R.,Simke, Leah R.,Thuy-Boun, Peter S.,Dixon, Darryl D.,Yu, Jin-Quan,Baran, Phil S.
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- Design, synthesis and biological evaluation of second-generation benzoylpiperidine derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors
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An interesting enzyme of the endocannabinoid system is monoacylglycerol lipase (MAGL). This enzyme, which metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG), has attracted great interest due to its involvement in several physiological and pathological processes, such as cancer progression. Experimental evidences highlighted some drawbacks associated with the use of irreversible MAGL inhibitors in vivo, therefore the research field concerning reversible inhibitors is rapidly growing. In the present manuscript, the class of benzoylpiperidine-based MAGL inhibitors was further expanded and optimized. Enzymatic assays identified some compounds in the low nanomolar range and steered molecular dynamics simulations predicted the dissociation itinerary of one of the best compounds from the enzyme, confirming the observed structure-activity relationship. Biological evaluation, including assays in intact U937 cells and competitive activity-based protein profiling experiments in mouse brain membranes, confirmed the selectivity of the selected compounds for MAGL versus other components of the endocannabinoid system. An antiproliferative ability in a panel of cancer cell lines highlighted their potential as potential anticancer agents. Future studies on the potential use of these compounds in the clinical setting are also supported by the inhibition of cell growth observed both in cancer organoids derived from high grade serous ovarian cancer patients and in pancreatic ductal adenocarcinoma primary cells, which showed genetic and histological features very similar to the primary tumors.
- Granchi, Carlotta,Bononi, Giulia,Ferrisi, Rebecca,Gori, Eleonora,Mantini, Giulia,Glasmacher, Sandra,Poli, Giulio,Palazzolo, Stefano,Caligiuri, Isabella,Rizzolio, Flavio,Canzonieri, Vincenzo,Perin, Tiziana,Gertsch, Jürg,Sodi, Andrea,Giovannetti, Elisa,Macchia, Marco,Minutolo, Filippo,Tuccinardi, Tiziano,Chicca, Andrea
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- Synthesis and characterization of π-extended porphyrins as potential precursors for the formation of columnar mesophases: Design principles for columnar mesophases need revision?
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A series of meso-a bridged extended porphyrins substituted with long aliphatic chains were synthesized and fully characterized. Two different synthetic strategies were tested to obtain the target structures. The synthetic steps were optimized in order to obtain scalable routes for the production of sufficient quantities of η-extended porphyrins for material science studies. The porphyrins were obtained either as free bases or complexed with Ni II or CuII. UV-Vis spectroscopy and polarized light microscopy was used for the analysis of the material properties of the η-extended porphyrins. The results obtained with our compounds are not compatible with the results reported in the literature. ARKAT-USA, Inc.
- Herzog, Beat,Neier, Reinhard
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- First general, direct, and regioselective synthesis of substituted methoxybenzoic acids by ortho metalation
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(Chemical Equation Presented) New general methodology of value in aromatic chemistry based on ortho-metalation sites in o-, m-, and p-anisic acids (1-3) (Scheme 1) is described. The metalation can be selectively directed to either of the ortho positions by varying the base, metalation temperature, and exposure times. Metalation of o-anisic acid (1) with s-BuLi/TMEDA in THF at -78°C occurs exclusively in the position adjacente to the carboxylate. On the other hand, a reversal of regioselectivity is observed with n-BuLi/t-BuOK. With LTMP at 0°C, the two directors of m-anisic acid (2) function in concert to direct introduction of the metal between them while n-BuLi/t-BuOK removes preferentially the proton located ortho to the methoxy and para to the carboxylate (H-4). s-BuLi/TMEDA reacts with p-anisic acid (3) exclusively in the vicinity of the carboxylate. According to these methodologies, routes to very simple methoxybenzoic acids with a variety of functionalities that are not easily accessible by other means have been developed (Table 1).
- Nguyen, Thi-Huu,Chau, Nguyet Trang Thanh,Castanet, Anne-Sophie,Nguyen, Kim Phi Phung,Mortier, Jacques
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p. 3419 - 3429
(2008/02/03)
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- Palladium-catalyzed methylation and arylation of sp2 and sp 3 C-H bonds in simple carboxylic acids
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The use of preformed sodium carboxylates as substrates led to the first observation of facile Pd-insertions into sp3 β-C-H bonds in simple aliphatic acids. Consequently, Pd-catalyzed methylation and arylation of o-C-H bonds in benzoic acids and β-C-H bonds in aliphatic acids using either a phenylboronate, methylboronic acid, or ArI have been achieved via a C-H activation/C-C coupling sequence. Copyright
- Giri, Ramesh,Maugel, Nathan,Li, Jiao-Jie,Wang, Dong-Hui,Breazzano, Steven P.,Saunders, Lindsey B.,Yu, Jin-Quan
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p. 3510 - 3511
(2007/10/03)
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- Toward a better understanding on the mechanism of ortholithiation. Tuning of selectivities in the metalation of meta-anisic acid by an appropriate choice of base
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(Chemical Equation Presented) If employed in THF at 0°C, LTMP metalates meta-anisic acid at the doubly activated position. In contrast, n-BuLi/t-BuOK deprotonates position C-4 preferentially at low temperature. Functionalization at C-6 requires protection of the C-2 site beforehand. As a result of these findings, a new mechanism is proposed for the heteroatom-directed ortholithiation of aromatic compounds.
- Nguyen, Thi-Huu,Chau, Nguyet Trang Thanh,Castanet, Anne-Sophie,Nguyen, Kim Phi Phung,Mortier, Jacques
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p. 2445 - 2448
(2007/10/03)
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- Some evidence in favour of an electron transfer mechanism in the TiO2 photosensitized oxidation of benzyl derivatives in aqueous media
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The structure and/or distribution of products from the TiO2-sensitized photooxidation of some benzyl derivatives in aerated and/or deaerated aqueous media and in the presence of Ag2SO4 are reported. The results suggest that the single electron transfer process from the substrate to the photogenerated hole, previously proposed in CH3CN, should also be operative on gradually going from aqueous CH3CN to pure water.
- Ranchella, Michele,Rol, Cesare,Sebastiani, Giovanni V.
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p. 311 - 315
(2007/10/03)
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- 2-Amino-3-(3'-hydroxy-phenyl)-propanols and salts thereof
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Compounds of the formula STR1 wherein R1 is hydrogen, chlorine, hydroxyl, trifluoromethyl, methyl or methoxy, and R2 is hydrogen, alkyl of 1 to 2 carbon atoms or benzyl; And non-toxic, pharmacologically acceptable acid addition salts
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