Synthesis and antibiotic activity of the tricyclic furo[3,2-c] isochromen-2-trione unit of the pyranonaphthoquinones.
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 microg/mL, respectively.
Bianchi
Darío A
DA
Instituto de Química Orgánica de Síntesis (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, República, Suipacha 531, S2002LRK Rosario, Argentina.
Sutich
Emma G
EG
Kaufman
Teodoro S
TS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006571:Heterocyclic Compounds; D009285:Naphthoquinones