A Concise Strategy Towards the Isochroman-g-Lactone Unit of the Naphthoquinone Antineoplasic Antibiotics

DARÍO A. BIANCHI; EMMA G. SUTICH; TEODORO S. KAUFMAN

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Elsevier

Lugar: Amsterdam; Año: 2004 vol. 14 p. 757 - 760

0960-894X

The elaboration and biological activity of 15, containing the proposed pharmacophore for the antibiotic activity of the pyranonaphthoquinones, are reported. The synthetic strategy involved acid-catalyzed lactonization of mandelate 17 for isochroman ring formation, in combination with a Wittig?oxa-Michael functionalization of isochroman-3-ol derivative 20, a lactonization involving configurational inversion of a benzylic alcohol and a final AgO oxidation. Compound 15 showed activity against Staphylococcus aureus and Bacillus subtilis with MIC of 64 and 32 mg/mL, respectively.