Olefin Metathesis−Iodoetherification−Dehydroiodination Strategy for Spiroketal Subunits of Polyether Antibiotics

Abstract

The convergent synthesis of two pentacyclic analogs of the polyether monensin A is described. Although different with respect to the configuration of the alcohol at the 3 position of the six membered ring of the spiroketal subunit, the configuration at the acetal center in both structures is unchanged and is consistent with the anomeric effect. The key synthetic steps are the coupling of two complex segments via an olefin metathesis, and the subsequent conversion of a dihydroxyalkene to the spiroketal through an iodoetherification-dehydroiodination sequence. The compatibility of these transformations with a variety of functional groups makes the overall strategy appropriate for highly substituted frameworks.

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…Treatment of the diol with iodonium dicollidine perchlorate (IDCP), followed by exposure to silver triflate in the presence of collidine affords the spiroacetals 154 in moderate to good yield as diastereomeric mixtures. This method was most recently applied in their synthesis of a simplified monensin analogue, polyether spiroacetal 156 [84]. Thus, two-step treatment of diol 155 under the established conditions provided spiroacetal 156 as a 2:1 mixture of epimers.…”