(+)- and (-)-mutisianthol: first total synthesis, absolute configuration, and antitumor activity.
Graziela G Bianco, Helena M C Ferraz, Arinice M Costa, Letícia V Costa-Lotufo, Cláudia Pessoa, Manoel O de Moraes, Marcus G Schrems, Andreas Pfaltz, Luiz F Silva
The first synthesis of the natural product (+)-mutisianthol was accomplished in 11 steps and in 21% overall yield from 2-methylanisole. The synthesis of its enantiomer was also performed in a similar overall yield. The absolute configuration of the sesquiterpene (+)-mutisianthol was assigned as (1S,3R). Key steps in the route are the asymmetric hydrogenation of a nonfunctionalized olefin using chiral iridium catalysts and the ring contraction of 1,2-dihydronaphthalenes using thallium(III) or iodine(III). The target molecules show moderate activity against the human tumor cell lines SF-295, HCT-8, and MDA-MB-435.
