Gram-Scale Total\nSynthesis of Carbazomycins A–D\nthrough Late-Stage Regioselective Demethylation of Aryl Methyl Ethers

Gram-scale total synthesis of carbazomycins\nA–D\nis described.\nThe total synthesis of carbazomycin A was achieved in 44% overall\nyield over six steps from symmetrical 5-chloro-1,2,3-trimethoxybenzene.\nThe key aryne-mediated carbazole formation and methylation steps provided\nthe multiply substituted carbazole. The regioselective demethylation\nof the trimethoxycarbazole was performed using boron trichloride.\nThereafter, the phenolic hydroxy group was converted into the methyl\ngroup to provide carbazomycin A. Subsequent installation of the methoxy\ngroup realized the total synthesis of carbazomycin D. Regioselective\ndemethylation was performed using 1-dodecanethiol, effecting the conversions\nof carbazomycins A and D into carbazomycins B and C, respectively.