| Abstract
| - The enantioselective total synthesis of the potentantiparasitic agent milbemycin D (1) has beenachieved.The spiroketal fragment is prepared through a novelspiroketalization of a hydroxy pyrone to set the anomericstereocenter and establish functionality for the stereocontrolledattachment and subsequent extension of the connectingchain between the spiroketal and the hexahydrobenzofuran fragment.The hexahydrobenzofuran fragment is constructedthrough the exploitation of a sequential electrophiliccyclization−[2,3]-sigmatropic rearrangement to close theoxygen-containing ring and incorporate the C5 hydroxyl. A lithium bromideaccelerated Wittig olefination joins the spiroketal-containing subunit and the hexahydrobenzofuran subunit at theC10,11 double bond in high yield. Subsequentoxidationof the C1 hydroxyl provides access to the seco acid, which smoothlyundergoes macrolactonization. The sensitiveC2 stereochemistry and the C3,4 double bond are incorporated withoutepimerization at C2 or migration of the C3,4double bond.
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