Total Synthesis of Tetarimycin A, (+/-)-Naphthacemycin A(9), and (+/-)-Fasamycin A: Structure-Activity Relationship Studies against Drug-Resistant Bacteria

Making use of a reductive olefin coupling reaction and Michael-Dieckmann condensation as two key operations, we have completed a concise total synthesis of tetarimycin A, (+/-)-naphthacemycin A(9), and (+/-)-fasamycin A in a highly convergent and practical protocol. Synthetic procedures thus developed have also been applied to provide related analogues for structure-activity relationship studies, thereby coming to the conclusion that the free hydroxyl group at C-10 is essential for exerting inhibitory activities against a panel of Gram-positive bacteria, including drug-resistant strains VRE and MRSA.