Synthesis of furonaphth[1,3]oxazine and furo[1,3]oxazinoquinoline derivatives as precursors for an o-quinonemethide structure and potential antitumor agents.

Abstract

The synthesis of dihydro furonaphth[1,3]oxazine derivatives 3 was performed through a Mannich-type condensation between 2-cyano-5-hydroxy-3-methylnaphtho[1,2]furan 2a, 1.5 eq of a primary amine and 3 eq of formaldehyde. Similarly, 2-cyano-5-hydroxy-3-methylfuro[2,3-f]quinoline 2b gave the dihydro furo[1,3]oxazino-quinoline compounds 4. Heating a mixture of the naphthofuran 2a, tert-butylamine and formaldehyde at toluene reflux led to the furonaphthoxazine 3e, which decomposes to afford an o-quinonemethide intermediate 5. The latter was trapped with 1-morpholinopropene to give a dihydro furonaphthopyran derivative 6. All compounds 2, 3, 4 and 6 were assayed for in vitro cytotoxic activity toward L 1210, MDA-MB 231 and PC tumor cells. Among them, furonaphth[1,3]oxazines 3b, 3c, and furo[1,3]oxazinoquinolines 4c, 4d showed significant activity against L 1210 cells, while furoquinoline 2b was the most cytotoxic compound towards all three cell lines.

• Authors: L Benameur, Z Bouaziz, P Nebois, M H Bartoli, M Boitard, H Fillion
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 44 Issue 3 Pg. 605-8 (Mar 1996) ISSN: 0009-2363 [Print] Japan
• PMID: 8882458 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Oxazines
• Quinolines

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Leukemia L1210 (drug therapy)
• Oxazines (chemical synthesis, pharmacology)
• Quinolines (chemical synthesis, pharmacology)
• Tumor Cells, Cultured