Enantiospecific formal total synthesis of the tumor and GSK-3 beta inhibiting alkaloid, (-)-agelastatin A.

Abstract

[reaction: see text] An enantiospecific total synthesis of Weinreb's advanced intermediate 2 for (-)-agelastatin A has been achieved from the Hough-Richardson aziridine 8. Noteworthy reactions in our sequence include the highly regioselective trans-diaxial ring-opening of 8 with azide ion to set up the vicinal diamido functionality present within (-)-2 and the Grubbs-Hoveyda ring-closing metathesis (RCM) reaction that was used to construct its cyclopentene core.

• Authors: Karl J Hale, Mathias M Domostoj, Derek A Tocher, Ed Irving, Feodor Scheinmann
• Journal: Organic letters (Org Lett) Vol. 5 Issue 16 Pg. 2927-30 (Aug 07 2003) ISSN: 1523-7060 [Print] United States
• PMID: 12889910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Enzyme Inhibitors
• Oxazolidinones
• agelastatin A
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Alkaloids (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Glycogen Synthase Kinase 3 (antagonists & inhibitors)
• Glycogen Synthase Kinase 3 beta
• Oxazolidinones (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism