Activation for Cleavage of DNA

Reprinted from CURRENT BIOLOGY, Vol 1, Nicolaou, Chemistry and biology of the calicheamicins, copyright 1994 with permission of Elsevier. 

Compounds capable of forming an enol react with imines from formaldehyde and a primary or secondary amine to yield /3-aminoaIkyl carbonyl componnds called Mannich bases. The following reaction of acetone, formaldehyde, and diethylamine is an example  

The Mannich reaction apparently proceeds through a variety of mechanisms depending on the reactants and the conditions that are employed. The mechanism below appears to operate in neutral or acidic media. Note the aspects in common with imine formation and with reactions of enols and carbonyl groups. 

Reaction of the secondary amine with the aldehyde forms a hemiaminal. 

The hemiaminal loses a molecule of water to form an iminium cation. 

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We shall see examples of biochemically relevant conjugate additions in The Chemistry of... Calicheamicin ji Activation for Cleavage of DNA (see Section 19.7B) and in The Chemistry of... A Suicide Enzyme Substrate (Section 19.8). 

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