Título:
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Convenient synthesis of C75, an inhibitor of FAS and CPT1
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Autor/a:
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Sánchez Zarzalejo, Carolina; Makowski, Kamil; Mera Nanín, Paula; Farràs i Soler, Jaume; Nicolás Galindo, Ernesto; Herrero Rodríguez, Laura; Asins Muñoz, Guillermina; Serra i Cucurull, Dolors; García Hegardt, Fausto; Ariza Piquer, Xavier; García Gómez, Jordi
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Otros autores:
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Universitat de Barcelona |
Abstract:
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C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier. |
Materia(s):
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-Inhibidors enzimàtics -Trastorns del metabolisme dels lípids -Càncer -Diabetis -Aprimament -Enzyme inhibitors -Lipid metabolism disorders -Cancer -Diabetes -Weight loss |
Derechos:
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(c) Sánchez Zarzalejo, Carolina et al., 2013
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Tipo de documento:
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Artículo Artículo - Versión aceptada |
Editor:
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Royal Society of Chemistry
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