Assignment of the Absolute Configuration of the Marine Pentacyclic Polyether (+)‐Enshuol by Total Synthesis

Abstract

Finding its true identity: The complete stereostructure of the marine pentacyclic triterpene polyether (+)‐enshuol is shown. Asymmetric total synthesis confirmed the configuration predicted on the basis of NMR spectroscopic data of the previously synthesized natural products aurilol and glabrescol, substructures of which are present in enshuol, and disproved an earlier prediction based on biogenetic considerations.

Squalene‐Derived Triterpene Polyethers from the Red Alga Laurencia omaezakiana

“…Although the absolute configurations at C(3), C(6), and C(7) of the 2,8-dioxabicyclo [5.4.0]undecane moiety were determined, the configurations at C(10) to C(22) remained unsettled 3 ). Recently, the structure of enshuol, including the absolute configuration, was established as formula 1 by the asymmetric total synthesis [4]. Further investigation of this species collected at Enoshima, Kanagawa Prefecture, led to the isolation of a novel tetracyclic polyether triterpene alcohol 2, which we named omaezakianol 3 ), along with 15,16-anhydrothyrsiferol 3 ) (3).…”

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

“…In another example, Morimoto et al 21 used only CSA in dichloromethane, at room temperature, to perform cyclization in cascades, from one tertiary hydroxyl group onto a bisepoxide, to produce two new tetrahydrofurans (Scheme 5).…”

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

“…After elaboration to the diepoxide 138, a Brønsted acid-catalyzed epoxide-opening cascade afforded the D and E rings of enshuol. Finally, reagent-controlled, silyl triflate-promoted opening of the trisubstituted epoxide 140 with a tertiary alcohol nucleophile via 6-endo cyclization [19] efficiently formed 141 and 142, containing the B ring of enshuol (Scheme 15.10) [178].…”

“…This approach promised good control over the direction of the cascade. Relying on the well-documented bromoetherification strategy to construct bromooxanes and bromooxepanes [76,177,178,185], Jamison and coworkers first examined diepoxide substrates 163, 164, and 167 featuring various terminating nucleophiles (Scheme 15.13a). When carried out in highly polar, non-nucleophilic solvents such as hexafluoro-iso-propanol, cyclization reactions of 163, 164, and 167 afforded the desired tricyclic products 165, 166, and 168, respectively, in good yields via all-endo epoxide-opening cascades, albeit as 1 : 1 mixtures of diastereomers resulting from non-stereoselective bromonium formation.…”