Q.66. - Organic Chemistry

Question

Question: Draw a stepwise mechanism for the following reaction, which was used in the synthesis of ezetimibe (Section 20.6), a drug used to treat patients with high cholesterol.

Step-by-Step Solution

Answer

Answer

Formation of enolate

Formation of the final product

Step 1: Organic synthesis of drugs

In drug synthesis, each synthetic step should be carefully chosen because even the change in enantiomer of a compound can make the product toxic.

Starting material for drugs are usually simple products that are easily available.

The use of asymmetric synthesis is highest in drug synthesis. Cyclization, oxidation, reduction, chain extension reaction are some of the main reactions of organic synthesis.

Step 2: Ezetimibe

Ezetimibe is used to treat high cholesterol and fat abnormalities. Generally, it is taken orally with dietary changes.

It inhibits the absorption of cholesterol by the intestine and belongs to a class of drugs called selective cholesterol absorption inhibitors.

The chemical formula of the drug is $C_{24}{H}_{21}{F}_{2}N{O}_3$  .

Step 3: Mechanism of the given reaction

In the first step, LDA abstracts a proton from dimethyl glutamate to form an enolate.

Formation of enolate

 

The enolate reacts with the second compound and the product thus formed undergoes internal cyclization followed by removal of alkoxide group to form the final product.

Formation of the final product