Studies towards the synthesis of polycyclic polyprenylated acylphloroglucinol natural products and variants
Embargo Date
2024-03-07
OA Version
Citation
Abstract
Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a large family of natural products with highly oxygenated and densely functionalized frameworks and broad range of biological activities. Due to these features, PPAP natural products have drawn significant synthetic attention in organic synthesis. The dissertation research herein describes the efforts towards the asymmetric synthesis of two series of PPAP natural products: 1) the type A PPAPs (–)-nemorosone and (–)-6-epi-garcimultiflorone A and 2) the spirocyclic polyprenylated acylphloroglucinol (spiro-PPAP) natural products hyperbeanols and their precursor hypercalin B.
Regiodivergent photocyclization of dearomatized acylphloroglucinol substrates has been investigated and developed to produce type A PPAP structures using an excited- state intramolecular proton transfer (ESIPT) process. Using this strategy, we achieved the enantioselective total syntheses of the type A PPAPs (–)-nemorosone and (–)-6-epi- garcimultiflorone A. Diverse photocyclization substrates have also been investigated leading to divergent photocyclization processes as a function of tether length.
Also, considerable progress has been made in achieving the first total synthesis of spiro-PPAP natural products and one precursor hypercalin B. The synthetic pathway utilized Cu(I)-mediated coupling of a dienone synthon to rapidly build the critical C-C bond, and stereoselective intramolecular radical cyclization/oxygen trapping cascade to construct the spirocyclic motif.