What is Green Chemistry?
Fig. 1: 12 Principles of Green Chemistry (Image provided by American Chemical Society).

Green Chemistry is a collection of principles designed to improve the ways in which chemistry is performed. John Anastas and Paul Warner worked together to establish the 12 basic principles encompassing the purpose and practice of Green Chemistry (Fig. 1).

In 2006, Codexis, Inc. received a Presidential Green Chemistry Challenge Award for using technology that greatly reduced cost and manufacturing waste of the synthesis of hydroxynitrile. Hydroxynitrile is the key chiral intermediate of atorvastatin, the active ingredient in Lipitor.

What is Lipitor?
Lipitor is a statin drug, one of a family of medications that helps lower "bad" (LDL's) cholesterol and in some cases raise "good" (HDL's) cholesterol. Cholesterol in adequate amounts is actually essential to survival. Its major functions include providing rigidity to cell membranes, enabling the synthesis of vitamin D, and serving as the basis of steroid hormones like testosterone and estrogen (Freeman, 2007).

Cholesterol is normally synthesized in the liver where it is converted from a lipid to a biologically usable compound called a lipoprotein. Our bodies will synthesize all the cholesterol we need. Cholesterol only becomes problematic if ingested in high amounts from diet where it is then deposited into the bloodstream as excess. Total cholesterol is calculated by the amount synthesized in the liver plus the amount ingested from diet minus the amount used up and excreted. Though there are genetic predispositions for high cholesterol and other possible factors, it is widely speculated that high-fat and high-cholesterol diets are the biggest contributors to the majority of individuals with high cholesterol (Freeman, 2007).

The active ingredient in Lipitor, atorvastatin, acts as a competitive inhibitor of the rate-limiting enzyme HMG-CoA reductase located in the liver and is responsible for controlling cholesterol synthesis in the liver. By inhibiting HMG-CoA reductase, cholesterol levels in the blood are effectively lowered due to the absence of cholesterol production in the liver.

How does the method developed by Codexis apply to Green Chemistry?
Green Chemistry Principle
Codexis, Inc. Method
1.) Design for energy efficiency
Operates under mild pH conditions, in ambient temperatures, and under normal atmospheric pressure. Also requires fewer unit operations eliminating multiple energy consuming steps from the previous process
2.) Catalysis
Uses highly enhanced selective biocatalytic enzymes
3.) Renewable feedstock
Enzymes derived from renewable resources
4.) Safer solvents and auxiliaries
Reaction performed in aqueous water solution
5.) Inherently safer chemistry for accident prevention
Eliminaties high-vaccuum fractional distillation and use of hydrogen gas, creating safer environmental conditions for workers
6.) Design for degradation
Enzymes, the catalysts of the reaction, are 100% biodegradable
7.) Reduce derivatives
Significantly less byproducts and waste produced compared to previous method

HOW: The Process