First Total Synthesis of the Benzotropolone/Bis(pulvinone) Natural Product Aurantricholone Exploiting New Strategies for Establishing Benzotropolones and Z-Configured Pulvinones

Abstract

Aurantricholone as well as its calcium and lithium salts, all of which represent the coloring principle of the fungus Tricholoma aurantium, were synthesized for the first time, namely in 15 steps, 10 of which were our longest linear sequence. We developed an access to benzotropolones after dibromocyclopropanating alkyl or silyl enol ethers of 1-tetralones. Successive treatments with DMAP-N-oxide and Ac2O effected ring-enlargement, oxidation, and acetylation. O-acetyl-1-bromo-3,4-dimethoxybenzotropolone obtained thereby – similarly as unsubstituted benzotropolone – was brominated at C-8 in two steps by adopting our recently published bromination protocol for otherwise unsubstituted O-acetylbenzotropolone. Thereafter, a double and doubly Z-selective Suzuki-coupling with a newly introduced boronate established the O-methylated pulvinone moiety as well as the O-methylated “pulvinone-like” motif of what altogether equaled the completed aurantricholone scaffold. Its deprotection (two steps) furnished the title compound either as its protonated form or its calcium or lithium salt.