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Convenient synthesis of C75, an inhibitor of FAS and CPT1 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 Inhibidors enzimàtics Trastorns del metabolisme dels lípids Càncer Diabetis Aprimament Enzyme inhibitors Lipid metabolism disorders Cancer Diabetes Weight loss 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. 2013-05-10T07:45:38Z 2014-04-17T22:02:18Z 2013-04-17 2013-05-07T14:30:04Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Versió postprint del document publicat a: http://dx.doi.org/10.1039/C3RA40913A RSC Advances, 2013, vol. 3, p. 6564-6571 http://dx.doi.org/10.1039/C3RA40913A (c) Sánchez Zarzalejo, Carolina et al., 2013 info:eu-repo/semantics/openAccess Royal Society of Chemistry Articles publicats en revistes (Química Inorgànica i Orgànica)