Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement.
A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A.
['David|Nadège|N|', 'Pasceri|Raffaele|R|', 'Kitson|Russell R A|RR|', 'Pradal|Alexandre|A|', 'Moody|Christopher J|CJ|http://orcid.org/0000-0003-0487-041X']
D001688:Biological Products D006576:Heterocyclic Compounds, 4 or More Rings D007211:Indoles D015394:Molecular Structure D010080:Oxazoles D010084:Oxidation-Reduction D000078183:Oxindoles D013237:Stereoisomerism
total synthesis natural products oxindoles