The Twelve Principles of Green Chemistry*

1. The Twelve Principles of Green Chemistry* • PreventionIt is better to prevent waste than to treat or clean up waste after it has been created. • Atom EconomySynthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product. • Less Hazardous Chemical SynthesesWherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment. • Designing Safer ChemicalsChemical products should be designed to effect their desired function while minimizing their toxicity. • Safer Solvents and AuxiliariesThe use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used. Chemistry in Water, so less organic solvents to store/handle This can be specific for each reaction – KRED chemistry is good example Most cells used are non-pathogenic and the solvent is generally water n/a Solvent = water *Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press: New York, 1998, p.30. By permission of Oxford University Press.

2. Many biocatalytic reactions at “room temperature” but rarely higher than 37 C • Design for Energy EfficiencyEnergy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure. • Use of Renewable FeedstocksA raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable. • Reduce DerivativesUnnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste. • CatalysisCatalytic reagents (as selective as possible) are superior to stoichiometric reagents. • Design for DegradationChemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment. The cells are grown with renewable resources (sugar, amino acids, etc.) Enzymes are stereo- regio- and enantiospecific. No need for these Enzymes are catalysts and cofactors are usually regenerated Pharmaceuticals often break this rule 

3. 11. Real-time analysis for Pollution PreventionAnalytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances. 12. Inherently Safer Chemistry for Accident PreventionSubstances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires. Biocatalysis usually doesn’t form “hazardous materials” When was the last time you heard a Budweiser plant exploded? No organic solvents (flammable) and chemistry at ambient temperature and pressure are the main reasons.

4. Traditional Biocatalytic This process uses: Methylene chloride Silylating agents Dane-salt protection Acylating agents E Factor = 15 Whereas: Waste stream is Mainly water and Inorganic salts E Factor = 5 Cefalexin or more commonly cephalexin is a first-generation cephalasporin antibiotic introduced in 1967 by Eli Lilly and Company. It is an orally administered agent It was first marketed as Keflex (Lilly). As of 2008, cefalexin was the most popular cephalosporin antibiotic in the United States, with more than 25 million prescriptions of its generic versions alone, for $255 million in sale.

6. Dehydrogenase should be on this list as well… It is one of the most characterized enzymes

7. spontaneous Racemic This epimerizes the chiral carbon This reaction eliminated 5 million gallons of organic solvents annually (THF, MeOH, EtOH)