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Green Chemistry and Benign by Design

7 ways to boost profits and reduce pharma synthesis waste

Neuland EHSAt Neuland, we’re advocates of green chemistry. Not only is it better for the environment, but it’s also just logistically simpler – in terms of infrastructure, health & safety, cost and more. The U.S. EPA’s Green Chemistry initiative – endorsed by the American Chemical Society – is a great example of a program geared towards promoting cleaner processes.

Synthesis can be a chemical- and solvent-heavy series of steps.  Whenever possible, Neuland Labs chooses synthetic pathways with the ‘Benign by Design’ concept in mind. Our approach to optimizing synthesis includes these 7 Aspects of Green Chemistry:

  1. Benign-by-Design Chemistry
    To minimize the impact on the environment, we design our manufacturing processes to maximize the use of the substrates and reagents, perform reactions at ambient temperature and pressure whenever possible, and reduce the use of noxious solvents. We choose chemicals and processes that are more environmentally friendly and sustainable. We use enzymes whenever possible to perform selective reactions and improve reaction efficiency.
  1. Sustainability-by-Design
    The stability of the product during its storage and use directly affects its overall impact on the environment and its cost.  Synthetic processes should be developed to maximize sustainability of the ingredients and stability of the product.  For example, the efficiency of plant-based substrates, which are sustainable substrates, can be tested and compared to synthetic oil-based substrates in the specific reactions.
  1. Design for Energy efficiency
    Chemical reactions often require heating or chilling to boost or decrease the reactivity of the components. Whenever possible, processes should be chosen that minimize the amount of needed energy. Depending on product and process characteristics, certain steps may be designed and run at ambient pressure and temperature.  For example, most enzymatic reactions can occur at room temperature or body temperatures and thus, save energy.
  1. Atom Economy
    At Neuland, our goal for reactions is to incorporate all components into the products. This is referred to as ‘atom economy’ or ‘atom efficiency.’  Essentially, we add substrates and catalysts (such as enzymes) in the correct proportion and then optimize the conditions in order for most atoms to be utilized. Even if yield is 100%, the formation of byproducts would reduce atom efficiency. For this reason, synthesis should be planned in such a way that minimum amounts of atoms are wasted.
  1. Reduction of Derivatives
    Chemical reactions often require protecting and deprotecting specific groups to focus the reaction to a specific site. However, each step uses reagents, and energy, and produces waste, therefore increasing cost.  Choosing synthetic pathways that minimize unnecessary derivatives can reduce the number of synthetic steps for derivation. This, in turn, reduces cost, time and waste.
  1. Bio/Enzymatic Catalysis
    Enzymes target specific substrates and rapidly modify them at specific molecular sites under ambient temperatures in often aqueous (water-based) solutions.  Other enzymes modify oils at specific molecular sites.   Whenever feasible, enzymes should be chosen to accomplish as many modifications as possible, due to their efficiency and low requirement for external energy. (e.g., a specific ketoreductase can be used to reduce required ketones asymmetrically, a specific transaminase can convert a ketone to an amine, or a specific lipase will hydrolyze the relevant ester.)
  1. Asymmetric Synthesis and Chiral pool synthesis
    In a chiral pool synthesis utilizing readily-available enatiopure substances, synthesis of complex enatiopure chemical compounds is carried out. The commonly used chiral starting materials are monosaccharides and amino acids.Enzymatic reactions may direct the synthesis to a specific isomer (asymmetric synthesis), providing much greater quantities of the desired active compound than the less desirable compounds.  In some cases, asymmetric substrates are available and can maximize the desired product in a process called chiral pool synthesis.  Using specific enzymes and available chiral substrates during the design and synthetic processes can maximize the yields of the target molecule(s).

At Neuland, we always choose the most efficient strategy for synthesis of specific isomers and commonly use a specific enzyme and /or chiral substrate to maximize yields of the biologically active compound.   We also employ Benign by Design Green Chemistry principles to guide the joint design of your synthetic compound.

How much consideration do you give to green chemistry in your pharma development programs?

 

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