Overview
Viridin is an antifungal metabolite of Gliocladium virens that was first reported in 1945. Belonging to a class of molecules known as furanosteroids, it has a characteristic highly strained electrophilic furan ring fused between C-4 and C-6 of the steroid framework. Members of this family, including wortmannin, are known to be potent, irreversible covalent inhibitors of phosphoinositide 3-kinases (PI3Ks).
Biosynthesis
The complete biosynthesis of viridin is not known. Through 2- 14 C mevalonic acid labeling studies, it has been shown that viridin is biosynthesized from a triterpenoid pathway, which starts from squalene, rather than a diterpenoid pathway. Incorporation of lanosterol into viridin has been described. Although the mechanisms and order of the remaining steps from lanosterol to viridin are not certain, these include the formation of the furan ring, the loss of C-13 and C-14 methyl groups, aromatization of the C-ring, removal of the side chain, and oxidation of the A-ring. Some of these steps may be analogous to pathways of other steroids. Loss of a hydrogen atom from C-15 during removal of the C-14 methyl group suggests a pathway similar to that of other steroid biosyntheses.
Analogous to the cholesterol pathway, the C-14 methyl group is lost as formic acid by action of sterol 14-demethylase. Though the C-13 methyl group isn't removed in the pathway of aldosterone, it is possible that viridin undergoes analogous oxidation at C-18 followed by loss of formic acid or decarboxylation to remove the C-13 methyl. Removal of the side chain has been shown to follow a mammalian pathway. It likely follows the pathway of androstenedione and oxidatively removes the side chain as acetic acid, resulting in a ketone on the D-ring. This suggests that the vicinal oxygenations at C-1 and C-2 are independent steps involving hydroxylation.