Multi-component assembly of the bicyclic core associated with the tRNA synthetase inhibitors SB-203207 and SB-203208. Application to the synthesis of biologically active analogues.
The ketone (+/-)-5, which embodies the bicyclic core associated with the title tRNA synthetase inhibitors 1 and 2, has been prepared via a three-component coupling reaction involving 2-(hydroxymethyl)cyclopent-2-enone (15), methylamine (6) and propiolamide (10); straightforward elaboration of the readily derived acetates (-)-21 and (+)-21 has provided the biologically active analogues 23 and 24, respectively, of the title compounds.
Banwell
M G
MG
Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia. mgb@rsc.anu.edu.au
Crasto
C F
CF
Easton
C J
CJ
Karoli
T
T
March
D R
DR
Nairn
M R
MR
O'Hanlon
P J
PJ
Oldham
M D
MD
Willis
A C
AC
Yue
W
W
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007192:Indenes / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007192:Indenes; C410786:SB 203207; C410787:SB 203208; D013449:Sulfonamides; D000604:Amino Acyl-tRNA Synthetases