The ansamycins: synthesis of the naphthoquinonoid nucleus of rifamycin W; crystal structure verification of a key naphthalenic intermediate

Abstract

1,4-Benzoquinone has been converted into 8-acetyl-5,7-dihydroxy-6-methyl-3-propionylamino-1,4–naphthoquinone (29) in six steps in an overall yield of 20%. A key reaction involves the dimethylation of the intermediate 8-acetyl-3-acetylamino-1,4,5,7-tetramethoxynaphthalene (9); the structure has been confirmed by X-ray crystallography. Steric crowding prevents acetylation of 3-acetyl-1,4,5,7-tetramethoxy-6-methylnaphthalene (18) with premixed acetic acid and trifluoroacetic anhydride; 8-acetyl-1,4,5,7-tetramethoxy-6-methylnaphthalene (22) is converted by the same reagent into compound (18) by acetyl migration.