Synthetic Methodology

New pathway to bisnoraldehyde (BNA) from waste soya bean residues. The original route to BNA uses heavy metal catalysts that generate toxic waste, which is harmful to human health and the environment. This novel route to BNA from soya bean residues uses bleach and a catalyst cofactor system. This new process generates a nontoxic, aqueous waste stream and recoverable organic solvents that can be reused. The process also avoids toxic reagents.

New synthetic methodology for ganciclovir, the main active component in Cytovene®. The conventional production process of ganciclovir was very wasteful and involved environmentally hazardous chemicals. CordenPharma Colorado developed the Guanine Triester (GTE) Process, a new method that climates the production of hazardous solid waste. This novel process introduces a recycling process of total recovery for 80% of inputs. The overall process is also more cost-efficient as it requires less monitoring and transportation of hazardous chemicals.

New process for the manufacturing of sertraline, the active ingredient of Zoloft®. Sertraline is traditionally manufactured through a three-step streamlined process. This process is relatively wasteful and has low efficiency. Pfizer has developed a new single-step manufacturing process with environmental and human safety improvements, high yields, and an extremely pure product. Using a new palladium catalyst reduces the use of raw materials. The process has better reagents economy and improved cost-efficiency. 

Plant cell fermentation (PCF®) synthetic method to produce paclitaxel, the active substance in Taxol. Paclitaxel is conventionally produces from a precursor extracted from the European yew tree. Isolating paclitaxel kills the tree during extraction because it requires stripping the bark. Yew bark also does not contain much of the precursor. BMS has developed a new method to manufacture the precursor through PCF®. The system uses renewable nutrients (sugars and amino acids) and operates under controlled conditions at ambient temperatures and pressures.

Enzymes that improve the production of Atorvastatin calcium, an essential building block of Lipitor. Atorvastatin calcium is produced through hydroxynitrile (HN). This conventional process yields less than 50% and requires hydrogen bromide (a hazardous chemical). Codexis introduces a new enzymatic pathway that consists of three bioengineered enzymes that reduce the original process to two steps. This new process by Codexis® works in mild conditions and produces significantly higher yields. It also reduces environmental and health hazards by producing fewer byproducts and waste.

Synthesis of sitagliptin for drug, Januvia, developed through a collaboration between Merck & Co., Inc. and Codexis, Inc. Januvia is used to treat type II diabetes. The active ingredient, sitagliptin, conventionally requires an expensive and energy-intensive crystallization and high-pressure step. These companies use transaminase enzymes to increase selectivity and efficiency and reduce overall waste. 

Four-step synthetic route for ibuprofen production. This company's four-step synthetic route is an alternative to the traditional six-step synthetic route. This new process has 90% atom efficiency compared to the original process with less than 40% atom efficiency. Using anhydrous hydrogen fluoride as a solvent and catalyst reduces the volume of generated waste and increases the reaction's selectivity. Anhydrous hydrogen can also be recovered and reused with 99.9% efficiency.

Improved synthesis of aprepitant, the active ingredient in Emend® — a drug that combats chemotherapy-induced nausea and vomiting. This new process assembles aprepitant in 3 highly atom-economical steps (compared to the traditional 6 steps) and nearly doubles the yield. Compared with the first-generation synthesis, this new route eliminates sodium cyanide, dimethyl titanocene, and gaseous ammonia. This new process also requires only 20% of the raw materials and water used in the original process, eliminating approximately 41,000 gallons of waste per 1,000 pounds of aprepitant.

Improved peptide manufacturing process of etelcalcetide, the active ingredient in, Parsabiv™— a drug for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease. This novel process reduces chemical solvent use by 71%, manufacturing operating time by 56%, and manufacturing costs by 76%. This could eliminate over 14,400 cubic meters of waste, including 750 cubic meters of aqueous waste, while increasing profits.

Improved synthesis of Prevymis™, a prescription medicine that helps prevent cytomegalovirus (CMV) infection and disease in adults who have received bone marrow transplants. This antiviral drug uses an improved chemical catalyst, increases the overall yield by 60%, reduces the PMI by 73%, reduces raw material costs by 93%, and reduces water usage by 90%. Merk claims this synthesis will result in the elimination of over 15,000 MT of waste over its lifetime. It should also decrease the product's carbon footprint and water usage by 89% and 90%, respectively.