A Stereoselective Photoinduced Cycloisomerization Inspired by Ophiobolin A

Abstract

A stereoselective synthetic entry point to the 5−8− 5 carbocyclic core of the ophiobolins was developed. This strategy exploits the chiral tertiary alcohol of ophiobolin A to guide assmebly of the 5−8−5 scaffold in a single step via a photoinitiated cycloisomerization. Mechanistic insights into the origin of stereocontrol in this reaction are described, as are efforts to elaborate the resultant fused 5−8−5 ring system to the pharmacophore of ophiobolin A.

The incredible story of ophiobolin A and sphaeropsidin A: two fungal terpenes from wilt-inducing phytotoxins to promising anticancer compounds

“…This strategy is based on the chiral tertiary alcohol of ophiobolin A, which induced the assembly of the 5-8-5 scaffold in a single step via a photoinitiated cycloisomerization. 106 However, for all these synthetic strategies, which involve several steps, the yield was not reported, they are not ecofriendly, are very expensive and not scalable to the industrial level. An alternative can be the production of ophiobolin A using a fermenter process, which requires the selection of the best ophiobolin A fungal producer, i.e., D. gigantea or B. maydis, and optimization of the growth conditions such as the medium, temperature, and light.…”

Therapeutic vulnerabilities of cancer stem cells and effects of natural products

“…7). 272 Ophiobolin A (Op A) possesses potent anti-cancer activity with 50% growth inhibitory concentrations (IC 50 ) ranging from 16 to 400 nM across the NCI's 60 cell line panel. 255,273 The known anti-cancer activity of natural ophiobolins and synthetic analogs support the notion that the 1,4-keto aldehyde moiety is responsible for the observed highly potent activity, giving rise to the hypothesis that ophiobolins might react with lysine residues of certain proteins via the Paal-Knorr reaction leading to their bioactivity.…”