Mapping the Chemistry of Highly Unsaturated Pyrone Polyketides

Abstract

C h e m i s t r y o f H i g h l y U n s a t u r a t e d P y r o n e P o l y k e t i d e s Abstract: Highly unsaturated pyrone polyketides ('HUPPs') are a growing family of natural products derived from polyene precursors, often through pericyclic or ionic reaction cascades. We describe our extensive studies on this class of compounds, which have so far resulted in the total synthesis of 17 of its members.

Syntheses of Conjugated Pyrones for the Enzymatic Assay of Lovastatin Nonaketide Synthase, an Iterative Polyketide Synthase

“…Although these compounds have been previously obtained by fermentation of fungal strains that have LNKS but no active LovC, the small amounts produced together with the instability of these pyrones make facile synthetic access desirable . Apparently, in contrast to polypropionate-derived unsaturated pyrones that bear additional methyl groups, these seemingly simple compounds decompose in a few hours at room temperature under acidic or basic aqueous conditions. In the present work, we report chemical syntheses of 3 and 4 and their use in an assay of LNKS.…”

“…In summary, facile syntheses of highly conjugated and unstable pyrones 3 and 4 have been completed and added to the repertoire of recent syntheses of other natural pyrones …”

Total Synthesis of the 2,5-Disubstituted γ-Pyrone E1 UAE Inhibitor Himeic Acid A

“…Although there are numerous γ-pyrone (4-pyrone) natural products that are known, , they are often polypropionate derived (e.g., aureothin, ocellapyrone A), contain oxygenated substituents (e.g., maltol or kojic acid), or contain ring fusion (e.g., flavonoids and isoflavonoids, which can be considered as benzo-fused γ-pyrones). Much less common are 2,5-disubstituted γ-pyrones.…”