- Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: Part 1
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In an effort to develop potent and selective inhibitors toward ACAT2, structure-activity relationship studies were carried out using derivatives based on pyripyropene A (PPPA, 1). We have successfully developed novel PPPA derivatives with a 7-O-substituted benzoyl substituent that significantly exhibit more potent ACAT2 inhibitory activity and higher ACAT2 isozyme selectivity than 1.
- Ohtawa, Masaki,Yamazaki, Hiroyuki,Ohte, Satoshi,Matsuda, Daisuke,Ohshiro, Taichi,Rudel, Lawrence L.,Omura, Satoshi,Tomoda, Hiroshi,Nagamitsu, Tohru
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- Stereoelectronics of silyloxybenzoic acids
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Synthetic organic chemists generally think of silyl ethers as easier-to-cleave alkyl ethers, frequently neglecting to consider both the unique facets of elemental silicon and the size of commonly used trialkylsilyl protecting groups. In this study, severa
- Varjosaari, Sami E.,Hess, Jeremy P.,Suating, Paolo,Price, John M.,Gilbert, Thomas M.,Adler, Marc J.
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- Ni-Catalyzed Carboxylation of C(sp2)-S Bonds with CO2: Evidence for the Multifaceted Role of Zn
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Nickel-catalyzed reductive carboxylation reactions of aryl electrophiles typically require the use of metallic reducing agents. At present, the prevailing perception is that these serve as both a source of electrons and as a source of Lewis acids that may aid CO2 insertion into the Ni-C bond. Herein, we provide evidence for the in situ formation of organometallic species from the metallic reductant, a step that has either been ruled out or has been unexplored in catalytic carboxylation reactions with metal powder reductants. Specifically, we demonstrate that Zn(0) acts as a reductant and that Zn(II) generates arylzinc species that might play a role in the C(sp2)-S carboxylation of arylsulfonium salts. Overall, the reductive Ni-catalyzed C(sp2)-S carboxylation reaction proceeds under mild conditions in a non-amide solvent, displays a wide substrate scope, and can be applied to the formal para C-H carboxylation of arenes.
- Yanagi, Tomoyuki,Somerville, Rosie J.,Nogi, Keisuke,Martin, Ruben,Yorimitsu, Hideki
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p. 2117 - 2123
(2020/02/28)
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- Transition-Metal-Free Decarboxylative Iodination: New Routes for Decarboxylative Oxidative Cross-Couplings
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Constructing products of high synthetic value from inexpensive and abundant starting materials is of great importance. Aryl iodides are essential building blocks for the synthesis of functional molecules, and efficient methods for their synthesis from chemical feedstocks are highly sought after. Here we report a low-cost decarboxylative iodination that occurs simply from readily available benzoic acids and I2. The reaction is scalable and the scope and robustness of the reaction is thoroughly examined. Mechanistic studies suggest that this reaction does not proceed via a radical mechanism, which is in contrast to classical Hunsdiecker-type decarboxylative halogenations. In addition, DFT studies allow comparisons to be made between our procedure and current transition-metal-catalyzed decarboxylations. The utility of this procedure is demonstrated in its application to oxidative cross-couplings of aromatics via decarboxylative/C-H or double decarboxylative activations that use I2 as the terminal oxidant. This strategy allows the preparation of biaryls previously inaccessible via decarboxylative methods and holds other advantages over existing decarboxylative oxidative couplings, as stoichiometric transition metals are avoided.
- Perry, Gregory J. P.,Quibell, Jacob M.,Panigrahi, Adyasha,Larrosa, Igor
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p. 11527 - 11536
(2017/08/30)
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- PYRIPYROPENE DERIVATIVE HAVING ACAT2-INHIBITING ACTIVITY
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The present invention is a compound having the general formula (I), (II), or (III) or a pharmacologically acceptable salt, solvate, or hydrate thereof, and a pharmaceutical composition containing such a compound, or its pharmacologically acceptable ester, or other pharmacologically acceptable derivative thereof as an active ingredient. The compound has an excellent ACAT 2-inihibiting activity by a mechanism different from that of a statin drug and is useful as a therapeutic or prophylactic agent for obesity, adiposis, hyperlipidemia, hypercholesterolemia, disorder of lipid metabolism, and arteriosclerosis, as well as obesity-derived hyperlipidemia, hypercholesterolemia, disorder of lipid metabolism, arteriosclerosis, and hypertension.
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Page/Page column 25
(2010/10/01)
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