Rapid cleavage of unactivated, unstrained amide bonds at neutral pH.
Building upon the discovery of Suggs and Pires that N-(2-hydroxyethyl)glycine amides undergo rapid amide cleavage under mild conditions [ Suggs, J. W. ; Pires, R. M. Tetrahedron Lett. 1997, 38, 2227-2230 ], we synthesized the derivatives (4aalpha,8beta,8aalpha)-1-ethylamido-8-hydroxydecahydroquinoline ( 4) and (4aalpha,8alpha,8abeta)-1-ethylamido-8-hydroxydecahydroquinoline ( 5). These two species are conformationally constrained, but steric compression is not introduced between the hydroxyl group and the amide functionality it attacks. At 20 degrees C and slightly basic pH, derivatives 4 and 5 undergo amide cleavage with half-lives of 21 min and 14 h, respectively, which correspond to rate increases of 251- and 6.3-fold relative to the acyclic analogue N-(2-hydroxyethyl)glycine amide ( 3).
Fernandes
Nicolette M
NM
Department of Chemistry, Amherst College, Amherst, Massachusetts 01002, USA.
Fache
Fabienne
F
Rosen
Mari
M
Nguyen
Phuong-Lan
PL
Hansen
David E
DE
D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008968:Molecular Conformation; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry
D000577:Amides; D011804:Quinolines; C018556:glycine amide; D010447:Peptide Hydrolases; D005998:Glycine