title: Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement.
abstract: 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.
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Nadège
authors.initials: N
authors.lastname: David
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pasceri
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Russell R A
authors.initials: RR
authors.lastname: Kitson
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pradal
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. c.j.moody@nottingham.ac.uk.
authors.forename: Christopher J
authors.identifier: http://orcid.org/0000-0003-0487-041X
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D010084:Oxidation-Reduction; D000078183:Oxindoles; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D010080:Oxazoles; D000078183:Oxindoles; C022960:2-oxindole; C408862:diazonamide A
keywords: natural products; oxindoles; total synthesis