Total syntheses of D-(+)-showdomycin and (+)-furanomycin

Abstract

Two total syntheses of D-(+)-showdomycin 1 have been accomplished starting from the enantiomerically pure syn-2,5-disubstituted dihydrofuran 44. Osmylation of 44 produced a-dihydroxylated tetrahydrofuran 45, which was subsequently treated with bromine in methanol and then thiophenol in the presence of p-TsOH to give thiophenyl furans 64. Treatment of 64 with bromine in THF followed by the sequential addition of aqueous t-butanol and bromine furnished dicarboxylic acid 73. D-(+)-showdomycin 1 was obtained from 73 by treatment with trifluoroacetic anhydride, ammonia, acetyl chloride and aqueous trifluoroacetic acid in sequence. Alternatively, furan 54 was oxidized with bromine in aqueous THF and chromium trioxide on celite in sequence to produce lactones 56. Treatment of 56 with hydroxylamine and then chloromethyl methyl ether provided oxime esters 88. Mesylation of the hydroxy groups of 88 and the subsequent elimination gave nitriles 89. Cyclization of the conjugated nitrile esters 89 followed by deprotection furnished D-(+)-showdomycin 1. Total synthesis of (+)-furanomycin 2 has been attained employing the mercury cation-promoted cyclizations of γ-hydroxy alkene 90 and homoallylic trichloroacetimidate 115a. Diol 90, prepared from dimethyl gave oxazoline 127. After complete hydrolysis of 127, the generated amino group was protected and then the hydroxyl group in 129 was eliminated to provide dihydrofuran 134. The reductive cleavage of N-O bond, oxidation of the resulting alcohol and deprotection in sequence gave (+)-furanomycin 2. For the synthesis of pamamycin-607 137, β-hydroxy alkene 184 was prepared by Wittig olefination of aldehyde 176 and phosphonium salt 183. However, cyclization of 184 with various electrophiles was unsuccessful.