Maleimide chemsitry with thiols - (Feb/13/2009 )
Does anyone know the reaction mechanism for thiol reaction with maleimides? Please advise,
The reaction forms a stable thiol ether linkage. How detailed do you want to know?
do the electrons from the double bond attack the cysteine or vice versa? Does it need to be in the protonated state?
In this reaction the double bond of maleimide undergoes an alkylation reaction with SH group. One of the carbone adjacent to the double bond undergoes a nucleophilic attack by a thiolate anion to generate the addition product. The optimal pH for the reaction is 6.5-7.5, at higher pH, it may cause ring opening of maleimide and increase tyhe chance of less selective reaction towards NH2. I hope this helps.
I always get lost in the organic chemsitry of it all. So in order for this reaction to occur, the thiol in the cysteine in the needs to be deprotonated in order to attack the carbon of the double bond, right?
This thread has been a tremendous help.
Would alcohols (ROH) or amines (RNH2) react the same way as thiols (RSH)? How's the competetion between them?