• Journal Article

Total synthesis of (±)-ginkgolide B

Citation

Crimmins, M. T., Pace, J. M., Nantermet, P. G., Kim-Meade, A. S., Thomas, J., Watterson, S. H., & Wagman, A. S. (1999). Total synthesis of (±)-ginkgolide B. Journal of the American Chemical Society, 121(43), 10249-10250. DOI: 10.1021/ja993013p

Abstract

Ginkgo biloba, termed the “living fossil” by Darwin, has ancestors dating to 230 million B.C.1 Extracts of Ginkgo biloba, which have been used as herbal medicines for 5000 years to treat a variety of conditions such as coughs, asthma, and circulatory disorders, are currently undergoing clinical evaluation for treatment of dementia.2 Ginkgolide B is the most potent platelet activating factor (PAF) antagonist of the ginkgo extracts, with an IC50 of 0.6 íM.3 The complex molecular architecture of ginkgolide B, which includes six rings, eleven stereogenic centers, ten oxygenated carbons, and four contiguous fully substituted carbons, is a daunting challenge for chemical synthesis. The diabolical disposition of functionality dictates that introduction of functional groups be judiciously orchestrated. The ginkgolides were first characterized in 1967,4 and the syntheses of ginkgolides A5 and B6 were reported by Corey and co-workers in 1988. The synthesis of the related compound, bilobalide, was also achieved by the Corey group7 as well as by our laboratory.8 Reported herein is the total synthesis of ginkgolide B utilizing the zinc-copper homoenolate9 and double diastereoselective intramolecular [2+2] photocycloaddition methodologies developed in our laboratories.1