A Total Synthesis of the Antibiotic DB-2073

Abstract

A convergent aromatic annulation strategy based on the Michael addition of the dimethyl-1,3-acetonedicarboxylate 1 anion to 2-hexynal 2, followed by a regiocontrolled Dieckmann-type cyclization, has been applied to a total synthesis of the antibiotic, DB-2073 I. This tandem annulation reaction generates the fully substituted aromatic intermediate 3, which was transformed by a five-step sequence to I. In recent years we have developed a total and a formal synthesis of mycophenolic acid [Covarrubias-Zúñiga, A.; González-Lucas, A. Tetrahedron Lett. 1998, 39, 2881; Covarrubias-Zúñiga, A.; Díaz-Domínguez, J.; Olguín-Uribe, J.S. Synthetic Communications 2001, 31, 1373.] using as key step tandem reactions based on Michael addition and intramolecular Dieckmann-cyclization; In this article we utilize this synthetic approach for the total synthesis of the resorcinol DB-2073 I. This tetrasubstituted resorcinol was isolated and purified from pseudomonas B-9004, showing antibacterial and antifungal activities [Kanda, N.; Ishizaki, N.I.; Oshima, M.; Handa, A.; Kitahara, T.J. Antibiotics 1975, 28, 935.]. The molecular formula of DB-2073 was established by spectroscopic methods [Kitahara, T.; Kanda, N. J. Antibiotics 1975, 28, 943.], as 2-hexyl-5-propyl-resorcinol I.