Study of the Oxidative Cleavage Proposed in the Biogenesis of Transtaganolides/Basiliolides: Pyran‐2‐one Aromaticity‐Mediated Regioselective Control and Biogenetic Implications

Abstract

The synthetic feasibility of the oxidative cleavage: epoxidation of 7‐O‐geranylscopoletin followed by electrocyclic ring‐opening, proposed in the biogenesis of transtaganolides/basiliolides is studied. Unlike the proposed pericyclic reactions, this pathway has not yet been addressed. Three synthetic strategies have been tested consisting of: i) Baeyer–Villiger oxidation of p‐quinoids, ii) hydrolysis of quinone monoketals, or iii) direct fragmentation by using oxygen donors. Oxidation of the benzene ring of hydroxylated coumarins has been achieved using peroxyacids, but cleavage took place between undesired positions. The aromaticity conservation of the pyran‐2‐one cycle during oxidation is the controlling factor of these observed regioselectivities. The use of a 4,5‐dihydroxy‐2‐methoxycinnamate model, in which the pyran‐2‐one ring does not exert influence on oxidation, has allowed the design of a synthetic sequence toward an analogue of the natural pyran‐2‐one isolated from Thapsia transtagana, key in the biogenesis. Mechanistic proposals for the obtained results as well as their biogenetic implications are raised.