The Synthetic Routes of Atorvastatin lactone

Atorvastatin lactone is a synthetic chemical compound that is commonly used to treat high cholesterol levels in the human body.
The compound is a semisynthetic derivative of a natural substance called lovastatin, which is obtained from the fungus Aspergillus terreus.
Atorvastatin lactone is used in the treatment of a range of cardiovascular conditions, including hypercholesterolemia and dyslipidemia, and has become one of the most widely prescribed drugs for these conditions.

The synthetic routes of atorvastatin lactone can be broadly classified into two categories: direct synthesis routes and indirect synthesis routes.

Direct Synthesis Routes

The direct synthesis routes involve the synthesis of atorvastatin lactone directly from readily available starting materials.
These routes typically involve a sequence of chemical reactions in which the individual steps are carefully controlled to ensure the desired product is obtained.

One of the most commonly used direct synthesis routes involves the use of p-nitrophenylchloride as the starting material.
This route involves the following steps:

1. Chlorination of p-nitrophenylchloride to form p-nitrophenyl-2,2-dichloride
2. Treatment of p-nitrophenyl-2,2-dichloride with sodium hydroxide to form p-nitrophenol
3. Reduction of p-nitrophenol using diisobutylaluminum hydride (DIBAL) to form p-nitrophenyloxyphenylmethylphosphonate
4. Treatment of p-nitrophenyloxyphenylmethylphosphonate with hydrogen chloride to form p-nitrophenyloxyphenylphosphate
5. Reduction of p-nitrophenyloxyphenylphosphate using lithium aluminum hydride (LiAlH4) to form p-nitrophenyloxyphenylmethylphosphonate
6. Treatment of p-nitrophenyloxyphenylmethylphosphonate with phenylboronic acid and palladium on barium sulfate (Pd/BaSO4) to form atorvastatin lactone.
   

Indirect Synthesis Routes

The indirect synthesis routes involve the synthesis of intermediate chemicals that are used as building blocks to synthesize atorvastatin lactone.
These routes typically involve a sequence of chemical reactions that are carefully controlled to ensure the desired product is obtained.

One of the most commonly used indirect synthesis routes involves the use of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) as the starting material.
This route involves the following steps:

1. Hydrogenation of HMG-CoA to form mevalonic acid
2. Treatment of mevalonic acid with bis(2-(dithiothreitol-S-yl) borate) to form mevaldehyde
3. Reduction of mevaldehyde using hydride reagents to form 3-methyl-2-[[4-(3-pyridyl)-2-oxo-oxazolidin-3-yl] methylene]-1,3-oxazolidine
4. Conversion of 3-methyl-2-[[4-(3-pyridyl)-2-oxo-oxazolidin-3-yl] methylene]-1,3-oxazolidine into 3-methyl-2-[[4-(3-methoxy-2-oxo-oxazolidin-4-yl) phenyl]methylene]-1,3-oxazolidine
5. Reduction of 3-methyl-2-[[4-(3-methoxy-2-oxo-oxazolidin-4-yl) phenyl]methylene]-1,3-