Q75E - Organic Chemistry (Mcmurry)

Question

The amino acid methionine is biosynthesized by a multistep route that includes reaction of an imine of pyridoxal phosphate (PLP) to give an unsaturated imine, which then reacts with cysteine. What kinds of reactions are occurring in the two steps?

Step-by-Step Solution

Answer

The reactions occurring in the two steps are:

1. Elimination to form the unsaturated imine

2. Conjugate addition of Cysteine to the imine

Step 1: Formation of imines

Imines are formed in a reversible, acid-catalyzed process that begins with nucleophilic addition of the primary amine to the carbonyl group, followed by transfer of a proton from nitrogen to oxygen to yield a neutral amino alcohol, or carbinolamine. Protonation of the carbinolamine oxygen by an acid catalyst then converts the OH into a better leaving group and E1-like loss of water produces an iminium ion. Loss of a proton from nitrogen gives the final product and regenerates the acid catalyst.

Step 2: Conjugate addition

Conjugate addition refers to the nucleophilic addition directed to electrophilic carbon of the C=C in an unsaturated systems. It is alternative to the direct nucleophilic addition in reactions of -$\alpha ,\beta$ unsaturated systems. This reaction works well with certain types of nucleophiles like alkoxide and cyanide ion.

Step 3: Reactions occurring in two steps

There are two reactions occurring in the biosynthesis of amino acid methionine. The multistep route involves

1. Elimination to form the unsaturated imine

Elimination to form the unsaturated imine

2. Conjugate addition of Cysteine to the imine

Conjugate addition of Cysteine to the imine