Biosynthesis of Ginkgolides

Early attempts to reveal the biosynthetic route of ginkgolides, using [2- C]-acetate and dl-[2- C]-mevalonate, suggested the overall terpenoid origin of ginkgoUdes, and it was believed that ginkgolides were biosynthesized through the conventional mevalonate pathway. However, only recently it was reaUzed that the two conventional precursors, dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP), can participate in what is now known as the nonmevalonate pathway. 

Recently, a key player in the ginkgolide biosynthesis has been isolated and characterized A cDNA that encodes G. biloba levopimaradiene synthase, a diterpene synthase involved in ginkgolide biosynthesis, was isolated and characterized. Similarly, a new geranylgeranyl diphosphate synthase gene from G. biloba, was characterized.  

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While Ginkgo biloba achieves total biosynthesis of ginkgolides with great ease, it is only recently that chemical synthesis of these compounds has been accomplished. Initially, only the synthesis of hexahydro-5/f-dicyclopen-ta[6,clfuran-5a(6//)-ol, which represents the main framework of ginkgolides (rings A,B,D), was achieved [185]. Recently, however, using a sophisticated... 

Nakanishi K, Habaguchi K 1971 Biosynthesis of ginkgolide B, its diterpenoid nature, and origin of the tert-butyl group. J Am Chem Soc 93 3546-3547... 

Schepmann, H. G. Pang, J. Matsuda, S. P. T. Cloning and characterization of Ginkgo biloba levopimaradiene synthase, which catalyzes the first comitted step in ginkgolide biosynthesis. Arch. Biochem. Biophys., 2001, 392 263-269. 

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