Fragmentation of the conjugate base of 2-(1-hydroxybenzyl)thiamin: does benzoylformate decarboxylase prevent orbital overlap to avoid it?
The base-catalyzed addition of thiamin to benzaldehyde produces 2-(1-hydroxybenzyl)thiamin (HBnT), but in neutral solution HBnT undergoes base-catalyzed irreversible fragmentation into pyrimidine and thiazole derivatives. The fragmentation (rather than elimination) occurs in proportion to the extent that N1' is protonated or alkylated. Generating the conjugate base of HBnT by decarboxylation surprisingly leads to fragmentation independent of the state of N1'. Therefore, a cationic state at N1' specifically promotes removal of the C2alpha proton rather than the fragmentation process itself. It is suggested that benzoylformate decarboxylase, which generates a similar intermediate, exerts stereoelectronic control of the conformation of the carbanion, blocking fragmentation and facilitating protonation.
Hu
Qingyan
Q
Davenport Chemical Laboratory, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6.
Kluger
Ronald
R
D002262:Carboxy-Lyases / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008333:Mandelic Acids / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D013831:Thiamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*
D008333:Mandelic Acids; D002262:Carboxy-Lyases; C019778:benzoylformate decarboxylase; D013831:Thiamine