Total synthesis of highly symmetric squalene-derived cytotoxic polyethers

In this review article, we report our recent contributions to the total synthesis of the highly symmetric squalene-derived cytotoxic triterpene polyethers, teurilene (3), (+)-14-deacetyl eurylene (1), (+)-eurylene (4), ()-glabrescol (5), and (-)-longilene peroxide (2), based on the concept of two-directional synthesis utilizing their intrinsic molecular symmetry as the fundamental strategy. In the course of these synthetic studies, syn oxidative cyclizations of bishomoallylic tertiary alcohols promoted by rhenium(VII) oxide have been accomplished with excellent diastereoselectivities. The critical trans or cis selectivity between the 2- and 5-positions of the tetrahydrofuran (THF) ring in the products has been observed, depending on the substrates employed. In addition, the meso structure 6 originally proposed by Jacobs et al. has been revised to the optically pure Q symmetric structure 5 through its enantioselective total synthesis. Furthermore, the unknown absolute configuration of longilene peroxide has been determined by this synthesis as shown in the structural formula 2.