title: Natural tetraponerines: a general synthesis and antiproliferative activity.
abstract: A stereocontrolled general methodology to access all natural tetraponerines from (+)-T1 to (+)-T8 is detailed. Two consecutive indium-mediated aminoallylations with the appropriate enantiomer of chiral N-tert-butylsulfinamide and a thermodynamic control at the aminal stereocenter allow the formation of each natural tetraponerine with excellent stereoselectivity. The use of 4-bromobutanal in the first aminoallylation leads to the formation of 5-6-5 tetraponerines, while 5-bromopentanal is required to build the scaffold of 6-6-5 tetraponerines. A cross-metathesis reaction of the second aminoallylation product with cis-3-hexene is used to elongate the side chain up to 5 carbons so as to prepare the tetraponerines T5 to T8. The anticancer activity of these heavier tetraponerines against four different carcinoma human cell lines is examined, observing a promising cytotoxic activity of (+)-T7 against breast carcinoma cell line MCF-7.
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante , Apdo. 99, 03080 Alicante, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Bosque
authors.forename: Jose C
authors.initials: JC
authors.lastname: Gonzalez-Gomez
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Loza
authors.forename: José
authors.initials: J
authors.lastname: Brea
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D006575:Heterocyclic Compounds, 3-Ring