Q.72. - Organic Chemistry

Question

Question: Draw a stepwise mechanism for the following reaction, one step in the synthesis of the cholesterol-lowering drug pitavastatin, marketed in Japan as a calcium salt under the name Livalo.

Step-by-Step Solution

Answer

Answer

Enolization

Protonation

Formation of the final product

Step 1: Drug synthesis

The synthesis of drugs is an important field in organic asymmetric synthesis. The majority of the drugs are asymmetric and the synthesis should produce the required enantiomer in high yield.

Each step in organic synthesis is called the synthetic step and the products of each step will be called the intermediates.

These intermediates are isolated and their structure is studied to find the effective synthesis route for a compound.

Step 2: Pitavastatin

Pitavastatin is a drug used to lower the amount of LDL cholesterol in the blood.

Along with diet and exercise, these drugs can also increase the amount of HDL in the blood.

It inhibits the enzyme HMG-CoA reductase which is used in the first step for cholesterol synthesis.

The chemical formula for the drug is $C_{24}{H}_{25}FN{O}_4$ .

Step 3: Mechanism of the given reaction

The reaction is initiated by the enolization of ketone which belongs to one of the reactants in the presence of an acid.

Enolization

The carbonyl group of the other compound is protonated in the presence of an acid.

Protonation

The enol and the protonated carbonyl react followed by the removal of the hydroxyl group as water.

Internal rearrangements in the molecule followed by hydrogen abstraction gives the final product.

Formation of the final product