title: Asymmetric total synthesis and antiproliferative activity of goniothalamin oxide isomers.
abstract: Goniothalamin oxide (1) is a styryl lactone which was isolated from bark and leaves of several Goniothalamus species. This natural product has some interesting biological properties such as larvicidal and tripanocidal activities. However, no studies on the antiproliferative profile of goniothalamin oxide (1) and its stereoisomers have been reported yet. Here, goniothalamin epoxide (1), isogoniothalamin epoxide (2) and their enantiomers were prepared via epoxidation of (R)-and (S)-goniothalamin (4). A 3:2 molar ratio in favor of goniothalamin oxide (1) and ent-1 was observed from (R)- and (S)-4, respectively, when 3-chloroperbenzoic acid (mCPBA) was employed while an increase to 6:1 molar ratio was achieved with (S,S)-Jacobsen's catalyst. Antiproliferative activity of these epoxides revealed that ent-isogoniothalamin oxide (ent-2) was the most active against the eight cancer cell lines studied. These results indicate that 6S, 7R and 8R absolute configurations are beneficial for the activity of these epoxides.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Estadual de Campinas, CP 6154, Campinas, SP 13083-970, Brazil.
authors.forename: Cilene
authors.initials: C
authors.lastname: Marquissolo
authors.forename: Angelo
authors.initials: A
authors.lastname: de Fátima
authors.forename: Luciana K
authors.initials: LK
authors.lastname: Kohn
authors.forename: Ana Lúcia T G
authors.initials: AL
authors.lastname: Ruiz
authors.forename: João Ernesto
authors.initials: JE
authors.lastname: de Carvalho
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Pilli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D002723:Chlorobenzoates / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D002723:Chlorobenzoates; D004852:Epoxy Compounds; D011753:Pyrones; C540871:goniothalamin epoxide; C103280:goniothalamin; C000433:3-chloroperbenzoic acid