Gram-Scale Total Synthesis of Carbazomycins A–D through Late-Stage Regioselective Demethylation of Aryl Methyl Ethers

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