Question

Predict the product of the reaction of valine with the following reagents: (a) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{OH}\), acid (b) Di-tert-butyl dicarbonate (c) \(\mathrm{KOH}, \mathrm{H}_{2} \mathrm{O}\) (d) \(\mathrm{CH}_{3} \mathrm{COCl}\), pyridine; then \(\mathrm{H}_{2} \mathrm{O}\)

Short answer

(a) Ethyl ester of valine; (b) N-tert-butoxycarbonyl-valine; (c) Valine potassium salt; (d) N-acetylvaline.

Step-by-step solution

Understand Valine Structure

Valine is an amino acid with the structure: NH₂-CH(COOH)-CH(CH₃)₂. It contains an amino group (NH₂), a carboxylic acid group (COOH), and a branched hydrocarbon side chain (CH(CH₃)₂).

Reaction with (a) \\(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{OH}\\), acid

The reaction with \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{OH}\) under acidic conditions typically leads to esterification. The carboxylic acid group of valine reacts with ethanol to form an ethyl ester. The product is NH₂-CH(CH₂CH₃OCO)-CH(CH₃)₂.

Reaction with (b) Di-tert-butyl dicarbonate

Di-tert-butyl dicarbonate is commonly used to protect amine groups by forming a carbamate. Valine reacts with it to protect the amino group, resulting in the product: NH(CO₂tBu)-CH(COOH)-CH(CH₃)₂, where tBu stands for tert-butyl.

Reaction with (c) \\(\mathrm{KOH}, \mathrm{H}_{2} \mathrm{O}\\)

KOH in water is a basic condition. It will deprotonate the carboxylic acid group, forming the carboxylate salt: NH₂-CH(COO⁻K⁺)-CH(CH₃)₂.

Reaction with (d) \\(\mathrm{CH}_{3} \mathrm{COCl}\\), pyridine; then \\(\mathrm{H}_{2} \mathrm{O}\\)

Acetyl chloride reacts with the amino group in the presence of pyridine to form an amide linkage. After hydrolysis, the product is NH(C(O)CH₃)-CH(COOH)-CH(CH₃)₂, which is N-acetylvaline.

Key concepts

Valine

Valine is an essential amino acid, which forms part of the building blocks of proteins. Its structure consists of a backbone similar to other amino acids: an amino group (\(-NH_2\)), a carboxylic acid group (\(-COOH\)), and a distinctive side chain. In valine, the side chain is branched and includes a hydrocarbon chain (\(-CH(CH_3)_2\)). This gives valine its unique properties, including making it non-polar and hydrophobic.

Valine plays crucial roles in supporting muscle growth and energy provision during intense physical activities. Due to its hydrophobic nature, valine is often found in the interior of proteins, stabilizing their structures in water-based environments by repelling water molecules.

Being a branched-chain amino acid (BCAA), valine, along with isoleucine and leucine, is vital in protein biosynthesis, regulation of blood sugar levels, and energy supply. Understanding valine's structure helps us predict its chemical reactions and the products formed from these reactions.

Esterification

Esterification is a chemical reaction that creates an ester from a carboxylic acid and an alcohol, typically in the presence of an acid catalyst. For valine, the esterification process involves its carboxylic acid group reacting with ethanol, an alcohol.

In this reaction:

• The hydroxyl group (\(-OH\)) of the carboxylic acid in valine is replaced by an ethoxy group (\(-OCH_2CH_3\)), forming an ethyl ester.
• The product retains the amino group because esterification primarily targets the carboxylic acid group.

This reaction produces a molecule described as NH₂-CH(CH₂CH₃OCO)-CH(CH₃)₂.

Understanding esterification is important in synthetic chemistry because it allows modifying the solubility and reactivity of amino acids, such as valine, for various applications in pharmaceuticals and biochemistry.

Protection of Amino Group

Protecting an amino group is a common practice in organic synthesis to prevent undesirable reactions occurring at the amino site. One compound that effectively achieves this is di-tert-butyl dicarbonate (Boc₂O), which protects the amino group by converting it into a carbamate.

When valine reacts with di-tert-butyl dicarbonate:

• The \(-NH_2\) group is transformed into \(-NH(CO)_2tBu\), making it less reactive.
• The resulting product is more stable when exposed to other potential reactants.

This transformation is essential for achieving selectivity in subsequent reactions without involving the amino group.

Such protection strategies are widely used in the field of peptidomimetics and protein engineering, allowing chemists to engineer specific modifications elsewhere in the molecule without accidental changes at the amino site.

Amide Formation

Amide formation involves the creation of an amide bond which is a pivotal process in organic chemistry and biology. This is especially crucial in synthesizing peptides and proteins.

In the case of valine, when it reacts with acetyl chloride {\((CH_3COCl)\)} in the presence of a base like pyridine:

• The carboxyl group (\(-COCl\)) of acetyl chloride forms a bond with the amino group (\(-NH_2\)) of valine, converting the \(-NH_2\) into \(-NH(C(O)CH_3)\).
• This results in an amide linkage, producing a molecule known as N-acetylvaline.

This reaction does not affect the carboxylic acid part of valine, as the reaction specificity is towards the amino group.

Amide bonds are found extensively in proteins, constituting the backbone links between amino acids. Therefore, learning about amide formation not only helps in peptide synthesis but also enhances our understanding of protein structure and function.