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Updated: Jan 13, 2026
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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
Facile conversion of tetracycline antibiotics to 4,11a-bridged derivatives via oxidative mannich cyclization
Jianxin Gu1, Ping Cai, Yumin Gong
1Vaccine Research & Early Development, Pfizer Biotherapeutics, Pearl River, NY, USA.
Abstract:
Treatment of a variety of tetracyclines (tigecycline, minocycline, tetracycline and doxycycline) with Ag(2)CO(3)/EDTA or Hg(OAc)(2) cleanly gave the 4,11a-bridged derivatives in high yields. The reactions proceeded through a novel, intramolecular Mannich cyclization of an iminium species generated by oxidation of the tertiary dimethylamino group at C(4) by Ag(I) or Hg(II). Tetracyclines without 5-OH-substitution (tigecycline, tetracycline and minocycline) gave the 4-OH-substituted, 4,11a-bridged compound, whereas doxycycline gave the 4-dimethylamino-substituted, 4,11a-bridged product. In the case of tetracycline, the 4,11a-bridged compound can equilibrate further to a 4,6-bridged hemiketal. Some of the bridged compounds underwent a novel decarboxylation--rearrangement sequence under acidic conditions to give tricyclic, open chain 1,4-quinoid compounds.
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