5 Stories We are Eager to Share

Q3 2019

1. Meet Our Catalysis Team

Meet Our Catalysis Team Pharmaron’s catalysis team is an energetic group that is quickly becoming our chemists’ best friends. This is because the group’s mission is to improve the working efficiency of chemists. And if there’s one thing our chemists would like to have more of—it is time.

The team’s mission is to optimize reaction conditions faster—more specifically, catalytic reactions. By collaborating with chemists at all stages of the drug R&D process, their goal is to optimize catalytic transformations, and in the process, make them more efficient, reliable and cost-effective. With an increasing collection of hundreds of catalysts and ligands, and access to specialized screening equipment, including the 24/96-well parallel reactor (which requires less than one milligram of starting material), the group tackles challenges quickly and provides results to chemists in just two days. These solutions have the potential to deliver compounds faster using more efficient processes with a higher probability of success.

The catalysis team has made a significant impact with increasing productivity across Pharmaron’s discovery and process chemistry departments. This is a result of the catalysis group’s extensive screening work, including Suzuki coupling, ?C-N coupling (Ullman, Buchwald coupling), C-H Borylation, photoredox and other key reaction types in modern organic chemistry. Every month the group carries out hundreds of reactions under thousands of conditions with an average success rate of around 50%.

Besides traditionally used metal catalysts, enzymes collections are becoming one of the powerful tools in their screening work. There are many success stories for both discovery and process chemistry. A recent request from our process development and manufacturing (PDM) scientists was to find an efficient way to generate a chiral alcohol. The original method required chiral SFC separation of the corresponding racemate. Attempts using asymmetric reduction with different chiral metal catalysts gave the best result of 74% ee and 56% yield. The catalysis team screened over fifty ketoreductases and found an enzyme that could selectively generate the desired enantiomer in 98% ee and quantitative yield. This enabled the PDM group to generate the desired chiral alcohol in a large quantity by using a green and efficient biotransformation.

Since the creation of the team in 2016, great strides have been made to utilize their expertise. A newsletter focused on new and useful catalysts is regularly distributed to the chemistry departments. Through a series of internal training seminars, key research topics are presented, including photoredox and electrochemical synthesis. Currently, the group is looking to expand its screening capacity by building up a state-of-the-art automated screening platform.

As one can imagine, the catalysis group is busy, but that doesn’t diminish their enthusiasm. The team thrives on knowing that they can help their colleagues and our partners with their knowledge, tools and expertise. “I love my job,” said Dr. Shi Li, Group Leader. “It’s a great feeling to be able to make big impact on so many projects.”
 
Leadership
The catalysis team is led by Dr. Shi Li. Dr. Li started working at Pharmaron in 2016. Prior to this, he was an Associate Professor at the State Key Laboratory of Organometallic Chemistry at the Shanghai Institute of Organic Chemistry (SIOC) and received his post-doctoral fellowship at the Catalysis Research Center at Hokkaido University in Japan. The management team also includes Dr. Kexin Yang and Dr. Wenqiong Wu.

2. Striving for Success

Pharmaron strives to be not just our client’s R&D service provider, but to be their partner. We thrive on seeing our partners grow—especially when we can be there every step of the way.

On June 6, Goldfinch announced the start of its Phase l clinical trial for GFB-887, a small molecule TRPC5 inhibitor to treat kidney diseases. Since Goldfinch’s inception in December 2016, Pharmaron has provided services in medicinal chemistry, DMPK, in vitro biology and process chemistry. For their clinical compound GFB-887, Pharmaron’s teams supported API manufacturing.

Written with permission by Goldfinch

3. Pharmaron's 9th Symposium: Synthetic and Medicinal Chemistry

On September 21, Pharmaron is holding its ninth annual symposium: Synthetic and Medicinal Chemistry. The symposium is an opportunity for our scientists and partners to learn from world-class researchers from both industry and academia. The esteemed group of presenters will discuss the latest advancements in synthetic and medicinal chemistry. The goal of this symposium is to spark innovation, as that is the foundation to Pharmaron’s continued success.

Symposium Speakers:
  • Dr. Kevin Campos, MSD, USA
    Innovations in Synthetic Chemistry at MSD: Striving for the Ideal Commercial Manufacturing Process
  • Dr. Werngard Czechtizky, AstraZeneca, Sweden
    Leveraging New Modalities for Respiratory: The Exciting Chemical Space between Small Molecules & Antibodies
  • Prof. Francois Diederich, ETH Zurich, Switzerland
    Molecular Recognition in Chemical and Biological Systems: Chemical Models and Biostructural Investigations
  • Dr. Michael Hahn, Bayer AG, Germany
    Discovery of a Novel Oral NO- and Heme-Independent sGC Activator BAY 1101042
  • Dr. Bayard R. Huck, Merck KGaA, Germany
    It’s a Small-Molecule World: Medicinal Chemistry Challenges and Opportunities for the Next Decade
  • Prof. Guosheng Liu, Shanghai Institute of Organic Chemistry, China
    Copper-Catalyzed Radical Relay for Asymmetric C-H Functionalization
  • Prof. David MacMillan, Princeton University, USA
    New Photoredox Reactions for Medicinal Chemistry and Biological
  • Dr. Jan Willem Thuring, Janssen Pharmaceutica Research & Development, Belgium
    Discovery of JNJ-64619178 as a Potent and Selective PRMT5 Inhibitor for the Treatment of Lung and Hematologic Cancers

4. Swing by the Gym

Amongst the sea of buildings at Pharmaron’s Beijing campus, you’ll find a hidden gem. Located in Building 18 is a full-service gym, where Pharmaron employees can conveniently workout before, during and after work.

In addition to the standard gym equipment, including weights, treadmills and stretch mats, there’s a room dedicated for classes. However, this isn’t your standard exercise room. Hanging securely from the ceiling are brightly colored fabric swings, which are used for aerial yoga classes. Aerial yoga incorporates the key elements from a traditional yoga, as well as Pilates and dance. With the use of the swing, deep stretches and poses that may not be feasible with a standard mat can be done with ease. Plus, it offers a unique and fun experience.

The gym provides a place for not only our team to unwind and exercise, but for visitors as well. Next time you are at the Beijing campus, we encourage you to swing by the gym!

5. Green Chemistry Success Story: Flow Chemistry

Flow chemistry is proving to be an ideal solution for some of our partners’ projects. But why? Simply put—flow chemistry provides consistent quality that is faster and cost-effective, in addition to being able to handle ‘forbidden’ reactions.

Flow chemistry is the process of having a chemical reaction run in a continuously flowing stream, rather than in batch production. The reagents are pumped into the flow reactor, which is composed of a tube or complex micro-structured device. Continuous flow through the reactor is maintained until the reaction is complete.

The key benefits from flow chemistry are cost, quality and safety. Small occupancy space, less energy and solvents, less waste generation, as well as about 30% fewer operators result in cost savings. In addition, flow chemistry enables excellent reaction selectivity and enhances safety due to its ability to maintain excellent mixing and heat transfer.

The members of Pharmaron’s flow chemistry team are seeing exciting results. A recent project had a reaction time reduced from 15 hours to 4 minutes and the isolation yield increased from 60% to 78%. In addition, less toxic waste was produced as only 4V of toluene was needed, compared to 10V of chlorobenzene for a batch production. Given the reaction’s high pressure and high temperature, this could not have been done with batch production, which made the outcome even more impressive.
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