Polyether formation cascades

A different mechanism was adopted in the biosynthesis of cyclic polyethers such as monensin. These PK-derived polycycles are formed in a cascade fashion with other enzymatic transformations. For example, in the biosynthesis of monensin (Equation 8.2), the cascade polyether formation is triggered by epoxidation of a polyene template [40]. Similar mechanisms can probably be used to make other polyether antibiotics containing tetrahydrofurans and tetrahydropyrans [41]. 

The Shi epoxidation has found several applications in total synthesis [15]. Particularly attractive are examples in which it has been used to establish the stereochemistry of polyepoxides which can undergo cascade cyclizations to polyether products, mimicking possible biosynthetic pathways. An example is the construction of the tetahydrofuran rings of the natural product glabrescol via highly stereoselective formation of the tetraepoxide 10 from the polyene 9 (Scheme 12.6) [22]. 

In 1983, Cane et al. postulated that polyether biosynthesis takes place as a two step process. The first of these steps was proposed to be the enzymatically polyepoxidation of an acyclic hydroxypolyene precursor, and the second comprised a cascade of intramolecular epoxide ring openings with formation of the polyether frame work. [1] For monensin A... 

Application of the method to the gold-catalyzed cascade cyclization of an allenic diepoxyalcohol proceeded with formation of three C-O bonds in one pot to furnish a tricyclic polyether (Scheme 4-100). 

Inspired by the postulated biogenesis of polyether compounds, a valuable cascade cyclization approach was developed on the predictable carbocation formation of the Nicholas reaction using very mild acidic conditions (silica gel as promoter) with excellent yields via very often inefficient epoxide opening cascade (13AGE3659). 

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