Fig. 5: Proposed initial steps in the conversion of levopimaradiene (2) to ginkgolides in G. biloba.
a The enzymes identified in this work, the suggested activity, and the identified pathway intermediates. The colors depicted in ginkgolactone D highlight the structural characteristics that match the final configuration in ginkgolide A, also colored correspondingly. Ginkgolactone D is shown in two different conformations for easier visualization of its conversion into ginkgolide A. b Possible reaction mechanism of the conversion of levopimaradiene (2) to ginkgosinoic acid A (7), the first suggested intermediate in the biosynthesis of ginkgolides. The proposal includes a radical ring opening followed by a similar hydrogen shift (H-shift) as the one proposed by Schwarz and Arigoni16. Oxygen rebound to quench the free radical (now at position C1) leads to an unstable intermediate that undergoes a second ring opening concomitant with water elimination. c Possible reaction mechanisms affording the C7–C8 to C7–C9 bond-shift in ginkgolide biosynthesis. Mechanism 1 is involving a dienone-phenol rearrangement starting with ginkgosinoic acid B. The proposed mechanism amounts to a classical NIH shift. Mechanism 2 depicts an alternative mechanism for the NIH shift, starting with epoxidation of ginkgosinoic acid B followed by acid-catalyzed opening of the epoxide. The localized carbocation is then stabilized by alkyl group migration, ultimately leading to ginkgosinoic acid C. d shows the relevant mechanism as proposed by Schwarz and Arigoni16, involving a dienone-phenol rearrangement of ferruginol towards ginkgolides.
