540-12-5Relevant articles and documents
Elongation of the Hydrophobic Chain as a Molecular Switch: Discovery of Capsaicin Derivatives and Endogenous Lipids as Potent Transient Receptor Potential Vanilloid Channel 2 Antagonists
Schiano Moriello, Aniello,López Chinarro, Silvia,Novo Fernández, Olalla,Eras, Jordi,Amodeo, Pietro,Canela-Garayoa, Ramon,Vitale, Rosa Maria,Di Marzo, Vincenzo,De Petrocellis, Luciano
, p. 8255 - 8281 (2018/09/25)
The transient receptor potential vanilloid type-2 (TRPV2) protein is a nonselective Ca2+ permeable channel member of the TRPV subfamily, still considered an orphan TRP channel due to the scarcity of available selective and potent pharmacological tools and endogenous modulators. Here we describe the discovery of novel synthetic long-chain capsaicin derivatives as potent TRPV2 antagonists in comparison to the totally inactive capsaicin, the role of their hydrophobic chain, and how the structure-activity relationships of such derivatives led, through a ligand-based approach, to the identification of endogenous long-chain fatty acid ethanolamides or primary amides acting as TRPV2 antagonists. Both synthetic and endogenous antagonists exhibited differential inhibition against known TRPV2 agonists characterized by distinct kinetic profiles. These findings represent the first example of both synthetic and naturally occurring TRPV2 modulators with efficacy in the submicromolar/low-micromolar range, which will be useful for clarifying the physiopathological roles of this receptor, its regulation, and its targeting in pathological conditions.
Intramolecular Cyclization of (ω-Carboxyalkyl)sulfonium Salts. A Novel Synthesis of Macrocyclic Lactones
Matsuyama, Haruo,Nakamura, Takako,Kamigata, Nobumasa
, p. 5218 - 5223 (2007/10/02)
A useful method for the synthesis of macrocyclic lactones using (ω-carboxyalkyl)sulfonium salts was developed.Base-catalyzed intramolecular cyclization of (ω-carboxyalkyl)diphenylsulfonium salts 2 gave simple macrocyclic lactones in high yields at high dilution conditions. (ω-Carboxyalkyl)alkylphenylsulfonium salts 8 afforded simple macrocyclic lactone 6a and alkyl carboxylates 9.The reactions of (ω-carboxyalkyl)dialkylsulfonium salts 10 gave only esters without lactonization product 6a.The cyclization of S-(ω-carboxyalkyl)thiolanium salts 3 and S-(ω-carboxyalkyl)-2-methylthiolanium salts 4 took place readily under similar conditions to afford sulfur-containing macrocyclic lactones 13 and 15, respectively, in good yields.To investigate the reaction mechanism, sulfonium salt 25, having an optically active carbon atom, was prepared.The intramolecular cyclization of 25 took place with an inversion of configuration at chiral carbon atom to give ricinelaidic acid lactone (26; optical purity 66percent).
Tin-mediated esterification in macrolide synthesis
Steliou,Poupart
, p. 7130 - 7138 (2007/10/02)
A neutral and relatively simple new method for effecting internal macrocyclic esterification of omega -hydroxycarboxylic acids, based on a tin 'template-driven' extrusion process, is discussed and its application to the synthesis (macrocyclization step) of the macrolide antibiotics zearalenone, ingramycin, and nodusmicin detailed. An efficient, formal total synthesis of pyrenophorin using this technique is also presented. Attempts to extend the methodology to include the macrocyclization of omega -bromo carboxylic acids or omega -mercapto carboxylic acids were unsuccessful. However, although beta - and omega -amino carboxylic acids preferentially gave way to polymer formation, 4-,5, and 6-amino carboxylic acids readily condensed to give the corresponding five-, six-, and seven-membered lactams in excellent yields. For example, in this way, the bridged lactam 1-azabicyclo- left bracket 3. 3. 1 right bracket nonan-2-one was prepared in 77% yield as compared to the previously reported yield of less than 2%.
