Exploitation of a Tuned Oxidation with N-Haloimides in the Synthesis of Caulibugulones A-D

Author(s)

Naciuk, Fabricio F. ^[1] ; Milan, Julio C. ^[1] ; Andreao, Almir ^[2] ; Miranda, Paulo C. M. L. ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[2] IFES, Aracruz, ES - Brazil

• Document type: Journal article
• Source: Journal of Organic Chemistry; v. 78, n. 10, p. 5026-5030, MAY 17 2013.
• Web of Science Citations: 7

Abstract

Marine alkaloids caulibugulones A-D were synthesized in six steps starting from the readily available 2,5-dimethoxybenzaldehyde. Pomeranz-Fritsch reaction of N-(2,S-dimethoxybenzyl)-N-(2,2-dimethoxyethyl)-2-nitrobenzenesulfonamide proceeded smoothly to give 5,8-dimethoxyisoquinoline, which was oxidized to isoquinolinadiones by a tunable oxidation reaction with N-haloimides. Therefore, NBS furnished direct conversion to the isoquinoline-5,8-dione; alternatively, N-haloimides of cyanuric acid provided both oxidation and halogenation generating 6,7-dihaloisoquinoline-5,8-diones. Aminolyses of these isoquinolinediones with methylamine or ethanolamine produced the isoquinolinedione alkaloids caulibugulones A-D in 24-57% overall yield. (AU)

• FAPESP's process: 09/51602-5 - Chemical biology: new natural and synthetic molecular targets against cancer, structural studies, biological evaluation and mode of action
• Grantee: Ronaldo Aloise Pilli
• Support Opportunities: Research Projects - Thematic Grants