Enshuol (1), a member of a family of squalene-derived triterpene polyethers named oxasqualenoids, [1] was isolated from the red alga Laurencia omaezakiana Masuda sp. by Suzuki and co-workers in 1995. [2] Although the planar structure and partial configuration of 1 were elucidated by spectroscopic and chemical analysis, until now the entire configuration had not been determined. Many other types of oxasqualenoids have been isolated; [1] however, it is often difficult to determine their stereostructures even by modern highly advanced spectroscopic methods, especially in the case of acyclic systems that include stereogenic quaternary carbon centers, such as C10รC11, C14รC15, and C18รC19 in 1. Such systems expose the technical limitations of the current highly advanced NMR spectroscopic methods used for the structural elucidation of diverse and complex natural products. [3] Such difficulties coupled with the unique structures of the oxasqualenoids have prompted synthetic organic chemists to determine the stereostructures of these natural products by chemical synthesis. [4] Herein, we report the total assignment of the previously incomplete stereostructure of (+)-enshuol (see structure 22) through the first asymmetric total synthesis of (+)-enshuol, the configuration of which is difficult to determine by other means.
Recently, we reported the assignment of the absolute configuration of (+)-intricatetraol (6) by chemical synthesis. [4h, 5] Biogenetic considerations led Suzuki et al. to suggest structure 5 for (+)-intricatetraol (Scheme 1). [6] Therefore, in this case, on the basis of the proposed biogenesis of 1, we chose compound 9 as the synthetic target. Too many stereostructures were possible for 1 if NMR spectroscopic data alone was considered. Suzuki and co-workers also suggested structure 9 to be the correct stereostructure of (+)-enshuol, again on the basis of the hypothetical biogenetic pathway.