Asymmetric Synthesis of Griffipavixanthone Employing a Chiral Phosphoric Acid-Catalyzed Cycloaddition

Abstract

Asymmetric synthesis of the biologically active xanthone dimer griffipavixanthone (GPX) is reported along with its absolute stereochemistry determination. Synthesis of the natural product is accomplished via dimerization of a p-quinone methide (p-QM) using a chiral phosphoric acid (CPA) catalyst to afford a protected precursor in excellent diastereo-and enantioselectivity. Mechanistic studies, including an unbiased computational investigation of chiral ion-pairs using parallel tempering (PT), were performed in order to probe the mode of asymmetric induction.

<p>Anti-Tumor Xanthones from <em>Garcinia nujiangensis</em> Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells</p>

“…7 This kind of metabolites showed numerous pharmacological activities such as anti-cancer, 8 antioxidant, 9 diuresis and saluresis, 10 hepatoprotective, 11 anti-gout, 12 anti-inflammatory, 13 anti-diabetes, 14 and gastroprotective. 15 Recently, these xanthones easily incorporated into micro-molecules attributing to intriguing biological activities had drew attention from phytochemical, 16 organic synthesis, 17,18 and pharmacological endeavors. 19 Xanthones from the genus Garcinia had structural diversity and exhibited significant biological activity.…”

Asymmetric Total Synthesis of Antibiotic Elansolid A

“…A subsequent dehydration would lead to the formation of a carbocation INT4, which was calculated to be in equilibrium with the protonated VQM species (Figure 5a). 18 This dehydration step should be reversible, as attested by the small energy difference (ΔΔG = 0.4 kcal/mol) between the forward and reverse reactions (see the Supporting Information for more details).…”

Recent advances in the synthesis of natural products containing the phloroglucinol motif

“…Baeckenon B (84), synthesized by Wang as illustrated in Scheme 14, serves as a key intermediate to generate baefrutones A-D (188)(189)(190)(191). Oxidative [4 + 2] cycloaddition between baeckenon B and (+)-thujene (187) in the presence of TEMPO and Ag 2 O generated the four natural products via two different oquinone methide intermediates (Scheme 36).…”

“…Natural Product Reports disclosed a biomimetic total synthesis of (AE)-griffipavixanthone 189 and shortly aer two years, the asymmetric synthesis of (+)-griffipavixanthone was reported by Schaus and Porco. 190 The strategy towards griffipavixanthone utilized 1,3,5-trimethoxybenzene ( 292 Scheme 55 Matsumoto's total synthesis of garcinone A.…”

“…186–188 In 2017, the Porco team disclosed a biomimetic total synthesis of (±)-griffipavixanthone 189 and shortly after two years, the asymmetric synthesis of (+)-griffipavixanthone was reported by Schaus and Porco. 190 The strategy towards griffipavixanthone utilized 1,3,5-trimethoxybenzene ( 292 ) as the starting material, condensed with 2,3-dihydroxy-4-methoxybenzoic acid ( 293 ) in the presence of Eaton's reagent to form the xanthone backbone. Demesylation, O -prenylation and thermal rearrangement of prenyl group then produced 294 .…”