Organic Chemistry

Module 5. Amino acids and peptides

Lesson 13
SYNTHETIC AND NATURAL AMINO ACIDS

13.1 Introduction

Amino acids which are obtained from natural sources, proteins are called natural amino acids. Amino acids which are synthesized by various methods are called synthetic amino acids. Because of the importance of amino acids in organic chemistry, bio-chemistry, medicine, food etc, a great deal of research has been devoted to develop methods for the synthesis of specific amino acids with the result most of the commercially available amino acids are prepared now-a-days synthetically.

Generally, a synthesis is a more convenient way of preparing an amino acid than preparing it from natural sources.

Several important methods for synthesizing α-amino acids are discussed below.

13.2 Amination of α-Halogenated Acids

An α-halogenated acid is treated with a large excess of ammonia. α-halogenated acids are more easily obtained by treating aliphatic carboxylic acids with chlorine or bromine in the presence of a small amount of phosphorous. Remember that in this reaction only α-hydrogen atom is replaced by halogen.

Glycine, alanine, serine, threonine, valine, and leucine, have been prepared by this method

13.3 Gabriel - Phthalimide Synthesis

Based on the "R" group present in α-halogenated acid ester the different kinds of amino acids will be formed.

If

R= H then it is Glycine.
R = CH₃- then it is Alanine.
R = (CH₃)₂CH- group (Isopropyl) then it is Valine.

and so on. As we change the "R" group attached to α-halogenated acid ester we get different kinds of amino acids.

13.4 Malonic Ester Synthesis

This method is really an extension of method no:1 as it offers a means of preparing α-halogenated acids. This method offers a means for preparing the following acids: phenylalanine, proline, leucine, iso-leucine, and methionine.

13.5 Phthalimidomalonic Ester Synthesis

This method is the combination of the previous two methods, malonic ester synthesis and Gabriel pthalimide synthesis.

In this method pthalimidomalonic ester (prepared from potassium phthalimide and monobromomalonic ester) is treated with the appropriate alkyl chloride in presence of sodium ethoxide and the product is hydrolysed to yield the amino acid.

Phenylalanine, cystine, tyrosine, proline, serine, aspartic acid, lysine and methionine have been synthesized by this method.

13.6 Strecker Synthesis

In this method an aldehyde or ketone is treated with a mixture of ammonium chloride and sodium cyanide (ammonium cyanide) to form cyanohydrin which on hydrolysis gives the corresponding amino acid.

This method is useful for preparing glycine , alanine, serine, valine, methionine, glutamic acid, leucine, and phenylalanine.