Enantiospecific formal total synthesis of the tumor and GSK-3 beta inhibiting alkaloid, (-)-agelastatin A.
[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.
Hale
Karl J
KJ
The Christopher Ingold Laboratories, University College London, 20 Gordon Street, London WC1H 0AJ, England. k.j.hale@ucl.ac.uk
Domostoj
Mathias M
MM
Tocher
Derek A
DA
Irving
Ed
E
Scheinmann
Feodor
F
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000470:Alkaloids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D023303:Oxazolidinones; C464968:agelastatin A; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3