Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement. Issue 31 (27th June 2016)

• Record Type: Journal Article
• Authors: David, Nadège; Pasceri, Raffaele; Kitson, Russell R. A.; Pradal, Alexandre; Moody, Christopher J.
• Is Part Of: Chemistry. Volume 22:Issue 31(2016)
• Page Start: 10867
• Page End: 10876
• Publication Date: 2016-06-27
• Subjects: oxindoles -- natural products -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201601605
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Totally indole darling ! A formal total synthesis of the complex marine metabolite diazonamide A has been completed. The route is different to previous approaches in that it is based on oxidative rearrangement of indoles