The photochemistry of pyrone natural products

Many marine mollusks of the Sacoglossan order have been found to contain pyrone polypropionates. These molecules are formally derived from propionate subunits, and are biosynthesized in the polyketide pathway. Wide speculation exists as to the biological function of these compounds, ranging from chemical defense to tissue regeneration. These polypropionates have been shown to undergo photochemical transformations in vivo. The purpose of this course of research was to explore the photochemical processes pyrone polypropionates undergo upon irradiation. The primary hypothesis was that these molecules undergo triplet photochemical processes. More specifically, we postulated that these gamma-pyrone natural products could behave as triplet photosensitizers. As such, we believed it possible that gamma-pyrone natural products could be responsible for generating singlet oxygen. If this hypothesis were correct, it might account for two observations: (1) the presence of peroxide and hydroperoxide natural products in these mollusks, and (2) the presence of cis-trans isomers of different polyene natural products. In order to test this hypothesis, it was necessary to first synthesize a pyrone natural product. To this end, we developed an alpha-methoxy-gamma-pyrone Horner-Wadsworth-Emmons reagent (58) that would expedite the synthesis of alpha-methoxy-gamma-pyrone polyenes. Using this versatile reagent, we prepared cyercene A (7), a natural product isolated from Cyerce cristallina. The sensitizing capabilities of cyercene A (7) and other pyrones were measured using sulfide oxidation studies with n-butyl sulfide and cis-trans isomerization studies with trans-1,3-pentadiene. Cyercene A (7) and other alpha-methoxy-gamma-pyrones were found to behave as triplet photosensitizers. It was also found that alpha-methoxy-gamma-pyrones regularly exhibited better sensitizing capabilities than their isomeric gamma-methoxy-alpha-pyrone counterparts. The sulfide oxidation method was particularly fruitful, as it also afforded a method to determine whether singlet oxygen was being produced. In each case studied, more sulfoxide was generated in the solution of the alpha-methoxy-gamma-pyrone than was generated in the blank solution, indicating that singlet oxygen was being produced upon aerobic photolysis of solutions containing alpha-methoxy-gamma-pyrones. Analysis of the photolyzed cyercene A (7) product mixture revealed that 4 was generated upon irradiation of cyercene A (7 ) under aerobic conditions. Furthermore, sunlight irradiation of a solution of cyercene A (7) yielded trace amounts of placidene A (3) and isoplacidene A (8), thus establishing that these placidene natural products may arise by way of cis-trans isomerizations of cyercene A (7).