Synthesis of Polyprenylated Benzoylphloroglucinols by Regioselective Prenylation of Phloroglucinol in an Aqueous Medium

Abstract

Regioselective tri‐C‐prenylation of phloroglucinol, leading to a compound with gem‐disubstitution, has been achieved with prenyl bromide in the presence of potassium hydroxide in an aqueous medium. Geranyl‐ and isolavandulylphloroglucinol, obtained by ortho‐lithiation, were diprenylated under the same conditions. C‐Benzoylation of the trialkylated derivatives using benzoyl cyanide in the presence of triethylamine afforded two natural products, grandone and kolanone, and an isomer of weddellianone A. Attemped electrophilic cyclization reactions, aimed at a biomimetic synthesis of polycyclic polyprenylated acylphloroglucinols (PPAPs), are also reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Inside Cover: Synthetic Active Site Model of the [NiFeSe] Hydrogenase (Chem. Eur. J. 22/2015)

“…Such cyclizations have been reported only in the case of systems lacking the full functionality of the natural products 5b,d,e. 8, 9 For example, Marazano and co‐workers could not isolate C‐cyclized products via cationic intermediates analogous to 6 8d. In a study by Couladouros and co‐workers,8e it was shown that unconjugated tertiary carbocations could not be cyclized to the [3.3.1]‐bicyclic core of 3 .…”

“…At the outset of our investigation, we had three principal concerns regarding the success of a protonative, cationic cyclization to access the bicyclo[3.3.1]nonane core: 1) control of O‐ versus C‐selectivity in the cyclization, 2) whether the O ‐methyl protecting group at C4 could direct cyclization at C1 to the nemorosone core, and 3) if 8 would rearomatize under acidic conditions given reports that similar dearomatized intermediates underwent rearomatization under acidic conditions 8a,d. We began our study by investigating an improved synthesis to acylphloroglucinol 9 which was previously prepared in 20 % yield from 11 by direct aromatic substitution 10.…”

A new synthesis of versatile indolyl-3-carbonylnitriles

“…Additional application of this method was demonstrated using 1-methylindole (entry 6) whose corresponding carbonyl nitrile (8) was synthesized in high yield via 16, and 2-methyl indole (entry 7), where the synthesis of intermediate (17) lowered the overall yield of 9.…”

“…[1][2][3][4][5][6][7][8][9] Specifically, the utility of indolyl-3-carbonylnitriles has been shown through their application to the synthesis of a variety of indole natural products ( Figure 1). [10][11][12][13] However, to date only two methods exist for the synthesis of indolyl-3-carbonylnitriles.…”

Synthetic efforts toward [3.3.1] bridged bicyclic phloroglucinol natural products

“…90 His only reported success forming the [3.3.1] carbocyclic skeleton using such an approach is shown in Scheme 72. Alkylation of pyrogallol ( 271 ) in water with prenyl bromide resulted in formation of fair amount of dearomatized bis -prenylated product 272 .…”