Bioinspired Total Synthesis Of Natural Products Epoxypyranones A And B

The secondary metabolites from fungi are the key source for searching leading compounds and small active molecules.Polyketone natural products with new skeleton feature 6/6/6/6/3 was isolated from the secondary metabolites of the Herpotrichia Species named epoxypyranones A-F,their biopathway can be speculated to be obtained through intermolecular Diels-Alder reaction between pyranone dienes and isochromone amphiphilic dienes.The compound epoxypyranones B-E has better anti neuritis activity IC₅₀ than the positive control quercetin.However,their source limited the study of mechanism to be carried out,thus it is important to synthesize it by chemical means.In this paper,according to the structural characteristics of the natural product,a key reaction of intermolecular Diels-Alder reaction of pyranone-diene and isochromone-amphiphilic was designed.（1）Researched the route for preparing pyranone dienes,starting from 5-bromo-4-methoxy-6-methyl-2H-pyranone-2-one,efficient synthesis of intermediate 5-（1-hydroxybutyl）-4-methoxy-6-methyl-2H-pyranone-2-one using isopropyl Grignard reagent for magnesium halide exchange and nucleophilic addition to n-butanal.Pyranone diene was obtained by intramolecular elimination reaction.（2）Explored the route of acid-base mediated dearomatization.The strategy of Friedel-Craft reaction,Achmatowicz rearrangement,group directed and dihydroxylation reaction tandem strategy were used as key reactions in the four routes to explore the synthesis of heterocyclic ketone dienes,but no key intermediates were obtained.（3）Explored the route of oxidative dearomatization and the 6πelectrocyclization tandem to synthesize isochromatic ketone dienophiles but no key intermediate was obtained.（4）Researched an efficient method for constructing brominated epoxycyclohexene diketones using the retro Diels-Alder reaction.Using Stille coupling to construct the required olefin chain for 6πelectrocyclization.Efficient synthesis of isochromone amphiphilic in 10 steps and synthesized natural product epoxypyranones series compound skeletons.（5）The obtained epoxypyranones skeletons were separated and identified including（±）-epoxypyranone A and epoxypyranone B and two unnatural isomers were obtained.