Total Synthesis of (±)-Ginkgolide B

Abstract

The total synthesis of the potent PAF antagonist ginkgolide B has been accomplished. The complex\narchitecture of ginkgolide B which includes six rings, eleven stereogenic centers, ten oxygenated carbons, and\nfour contiguous fully substituted carbons is a daunting challenge for chemical synthesis. The synthesis of\nginkgolide B was accomplished through a stereoselective intramolecular photocycloaddition of enone <b>5</b> to\nconstruct the congested core of the molecule. The photocycloaddition substrate was prepared through technology\nfor the construction of carboalkoxycyclopentenones previously reported from these laboratories. Regioselective\ncyclobutane fragmentation and further functionalization of the photoadduct <b>4</b> provided the key pentacyclic\nintermediate. Acid-catalyzed rearrangement and epoxide opening were key transformations in the production\nof ginkgolide B from the pentacyclic intermediate.