Synthesis of 8-Phenylphenalenones: 2-Hydroxy-8-(4-hydroxyphenyl)-1H-phenalen-1-one from Eichhornia crassipes

Abstract

2-Hydroxy-8-(4-hydroxyphenyl)-1H-phenalen-1-one (1), the first reported 8-phenylphenalenone from the roots of Eichhornia crassipes (water hyacinth), was synthesized starting from 2-methoxynaphthalene in 11 steps and with an overall yield of 2%. A cascade Friedel-Crafts/Michael annulation reaction between acryloyl chloride and 2-methoxynaphthalene afforded 9-methoxyperinaphthanone that, after transformation to 9-methoxy-2-(4-methoxyphenyl)-1H-phenalen-1-one by means of standard Suzuki-Miyaura methodology, was subjected to a reductive carbonyl transposition to afford 8-(4-methoxyphenyl)perinaphthanone. Dehydrogenation, epoxidation, and demethylation of the latter afforded 1.

Concise Synthesis of Natural Phenylphenalenone Phytoalexins and a Regioisomer

“…In summary, a concise and efficient strategy for the total synthesis of 2-hydroxy-8-(4-hydroxyphenyl)­phenalen-1-one ( 1 ), 2-hydroxy-8-(3,4-dihydroxyphenyl)­phenalen-1-one ( 2 ), the originally proposed structure of emenolone ( 3 ), and hydroxyanigorufone ( 4 ) was developed by starting from their corresponding naphthaldehydes ( 13 – 15 ) with the application of Friedel–Crafts acylation and Suzuki cross-coupling as the key reactions. The observed overall yield of 1 (11%) is much higher than the reported yield (1.43%) . This is the first report of the total synthesis of compounds 2 and 3 .…”

“…Research by others has led to the synthesis of 4- and 9-phenylphenalenones , and 2-hydroxy-8-(4-hydroxyphenyl)-1 H -phenalen-1-one ( 1 ) . The latter synthesis was achieved in 11 steps by Otålvaro and co-workers in 2015, but the overall yield was less than 1.5%, and the final product needed purification by repeated preparative TLC. This limits the potential applications of 8-phenylphenalenones in agricultural or clinical use.…”

Application of the Crystalline Sponge Method to Revise the Structure of the Phenalenone Fuliginone

“…Pharmacological [ 7 ], antimicrobial [ 1 , 8 ] and radical scavenging activities [ 9 ] have been also reported. Therefore, new phenylphenalenones and related compounds from natural [ 1 , 8 , 10 ] or synthetic sources [ 11 , 12 ] are desirable.…”

Phytotoxicity of Schiekia timida Seed Extracts, a Mixture of Phenylphenalenones

“…The commercial use of phenylphenalenone scaffolds would only be practical without the need of isolating them from natural sources, as they are normally biosynthesized in extremely low amounts in plants. Efforts to synthesize these compounds have been made [ 47 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ], but the high concentration of phenylphenalenones found in methanolic extracts of S. timida seeds raises the possibility of using this species as an alternative source of phenylphenalenones scaffolds.…”