Question

Show how you would use the Strecker synthesis to make isoleucine. What stereochemistry would you expect in your synthetic product?

Short answer

The Strecker synthesis is a two-step procedure for the synthesis of amino acids. An aldehyde on reaction with sodium cyanide or potassium cyanide in the presence of ammonia or ammonium chloride yields alpha-amino nitrile. Hydrolysis of alpha-amino nitrile in acidic medium forms alpha-amino carboxylic acid. By varying the “R” group on the aldehyde, a wide variety of amino acids may be made this way.

Step-by-step solution

Step-1. Strecker synthesis:

The Strecker synthesis is a two-step procedure for the synthesis of amino acids. An aldehyde on reaction with sodium cyanide or potassium cyanide in the presence of ammonia or ammonium chloride yields alpha-amino nitrile. Hydrolysis of alpha-amino nitrile in acidic medium forms alpha-amino carboxylic acid. By varying the “R” group on the aldehyde, a wide variety of amino acids may be made this way.

Step-2. Strecker synthesis of isoleucine and related stereochemistry:

2-methylbutanal on reaction with ammonium chloride and sodium cyanide, forms alpha-amino nitrile in first step. Cyanide ion acts as a nucleophile and attacks at the carbonyl carbon which is electrophilic in nature which leads to formation of alpha-amino nitrile after the substitution of amino group. In next step, hydrolysis of alpha-amino nitrile takes place which hydrolyses the cyano group to carboxylic acid group and in the final structure, isoleucine is represented in zwitter ionic form.

The stereochemistry of groups will remain unchanged as no reaction occurs at the chiral center in alpha-amino nitrile, since cyano group is getting hydrolysed to carboxylic acid group, no bond breaking is taking place. Thus, stereochemistry of groups will not change.

Synthesis of isoleucine by Strecker synthesis