Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1

J. D. Chisholm, D. L. Van Vranken

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

The indolo[2,3-α]carbazole glycosides are potent antitumor antibiotics currently undergoing clinical trials for the treatment of numerous types of cancer. AT2433-A1 is the most complex member of this family of compounds possessing a unique disaccharide with a sensitive aminodeoxysugar and an unsymmetric aglycon. The synthesis of this natural product requires a method for glycosylation that sets the stereochemistry of the anomeric center and the regiochemistry of the aglycon. These goals were accomplished by carrying out the Mannich cyclization of a bis-3,4-(3-indolyl)succinimide to give a key class of indoline intermediates that could be glycosylated stereoselectively with complex carbohydrates without hydroxyl protection or activation. The regiochemistry of the Mannich cyclization was precisely controlled by choosing between kinetic or thermodynamic conditions. This strategy culminated in the first synthesis of the antitumor antibiotic AT2433-A1.

Original languageEnglish (US)
Pages (from-to)7541-7553
Number of pages13
JournalJournal of Organic Chemistry
Volume65
Issue number22
DOIs
StatePublished - Nov 3 2000
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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