Spiroketals as natural product mimics and progress toward the total synthesis of milbemcyin beta14

A modular synthesis of spiroketals is herein reported. The synthesis allows for stereocontroled introduction of substituents in strategic positions about the pyran rings. The modular approach provides quick synthetic access to stereodefined fragments which can be coupled in various combinations to provide the carbon backbone of a library of spiroketals. Goals of the project include predictable and specified vector relationships between functionalized substituents about the spiroketal scaffold. Spiroketals were chosen as scaffolds due to the three dimensional rigidity resulting from the energetic stabilization called the anomeric effect. The synthetic route to spiroketals is adapted to the synthesis of the spiroketal fragment of the natural product milbemycin beta 14. Progress toward the total synthesis is reported.