Bosque, Irene, Gonzalez-Gomez, Jose C., Loza, María Isabel, Brea, José
Natural Tetraponerines: A General Synthesis and Antiproliferative Activity
Journal of Organic Chemistry. 2014, 79(9): 3982-3991. doi:10.1021/jo500446f
URI: http://hdl.handle.net/10045/46330
DOI: 10.1021/jo500446f
ISSN: 0022-3263 (Print)
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.
Keywords:Natural tetraponerines, Synthesis, Antiproliferative
American Chemical Society
info:eu-repo/semantics/article