Approach to the Core Structure of Schweinfurthin B

Abstract

We investigated approaches to the xanthene part of schweinfurthin B. Starting from an exo‐methylene cyclohexanone, an organocuprate addition led to a cyclohexanone featuring a functionalized benzyl substituent in the 2‐position. Ring‐closing reactions to the tetrahydroxanthene core (formation of the central ring) were possible in moderate yield by attack of a phenolic oxygen function on the keto group. More effective was the cyclization to the xanthene core structure after conversion of the cyclohexanone to the exo‐methylene cyclohexane derivative and Lewis acid mediated addition of the phenolic OH to the double bond. In addition, we tried to form the xanthene ring system in a model study by cycloaddition reaction of a silyl enol ether with an ortho‐quinone methide.

Synthesis of a Coumarin-Based Analogue of Schweinfurthin F

“…Although several disconnections have been explored for schweinfurthin assembly, 1 , 22 , 23 we have favored use of late-stage Horner–Wadsworth–Emmons (HWE) condensation to form the central stilbene olefin because this approach allows a highly convergent synthesis. From this perspective, the coumarin-containing schweinfurthin F analogue 13 could be seen arising from an HWE olefination between phosphonate 15 and aldehyde 16 ( Scheme 1 ).…”

“…All other reagents and solvents were purchased from commercial sources and used without further purification. The nuclear magnetic resonance (NMR) spectra were obtained on 300, 400, or 600 MHz Bruker spectrometers with Si(CH 3 ) 4 ( 1 H, δ 0.00), 4-Bromo-3,5-dihydroxybenzoic Acid (23). To an oven-dried and argon-purged round-bottom flask containing 3,5-dihydroxybenzoic acid (22, 10.0 g, 64.5 mmol) was added aqueous 20% HCl (110 mL) followed by a dropwise addition of bromine (3.31 mL, 64.5 mmol).…”