Catalyst Screening

• Currently, the vast majority of drugs are produced through organic synthesis. However, due to high costs, low success rates, and long turnaround times, organic synthesis has become the primary limiting factor in the preclinical development of new drugs.
  In chemical synthesis, metal-catalyzed reactions, especially transition metal-catalyzed coupling reactions, can quickly and precisely form various carbon-carbon bonds and carbon-heteroatom bonds, making it an efficient and broad-spectrum synthetic method. According to recent statistics, alkylation/arylation of heteroatoms and the formation of carbon-carbon bonds rank among the top five most utilized organic reactions. However, the failure rate of metal-catalyzed coupling reactions is high due to the diversity and complexity of substrates, and because heterocyclic rings in many drug-like molecules tend to poison metal catalysts. For instance, the reaction failure rate for carbon-nitrogen coupling exceeds 50%. The urgent need in drug discovery is how to efficiently and consistently produce a large number of compounds with limited intermediates within a restricted timeframe.
  To further enhance the efficiency of chemical synthesis and acquire more precise synthesis data, Shanghai Medicilon Inc. (Medicilon) has established a catalyst screening service platform. This platform assists our clients and chemists in swiftly identifying one or more effective chemical synthesis pathways, thereby lowering costs and boosting the efficiency of drug development.

Catalyst Screening Reaction Type

• Metal-catalyzed coupling reactions are common reactions used to form carbon-carbon bonds and carbon-heteroatom bonds in organic synthesis, playing a vital role in organic synthesis.

  (1) C-C Bond Formation

  Suzuki Reaction

  
  

  Heck Reaction

  
  

  Sonogashira Reaction

  
  

  Stille Reaction

  
  

  Negishi Reaction

  
  

  C-H Activation Reaction

  
  

  Cyanide Reaction

  
  

  Olefin Metathesis

  
  

  Photoredox

  
  

  (2) C-X Bond Formation

  Buchwald Reaction

  
  

  Ullmann Reaction

  
  

  Miyaura Reaction

  
  

  C-O

  
  

  C-S

  
  

Catalyst Screening Flowchart

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  A 72-hour working process was established for routine catalyst screening; we plan to shorten the timeline to 48 hours in the future.

Schematic Diagram of Catalyst Screening

Advantages of Catalyst Screening Service Platform

• (1) The catalytic turnover rate is high, allowing screening of multiple reaction conditions simultaneously, effectively reducing compound synthesis time.(2) The data accuracy rate is high, supported by experienced chemical synthesis experts, ensuring more accurate and reliable data.(3) Screening is cost-effective, requiring only a small amount of substrate for completion, which significantly reduces material and labor costs.

Catalyst Screening Equipment

Medicilon Case Study

• Medicilon Case Study 1: Suzuki Coupling

  
  

• Medicilon Case Study 2: Buchwald Coupling

  
  
  The parallel screening of 24 reaction conditions was completed with only a small amount of sample (around 50 mg) and a short period (2-3 days), resulting in the determination of the optimal reaction condition. Setting up 24 reactions separately would require significantly more samples and time than the current method.
  From the cases above, it is evident that catalyst screening plays an important role in the synthesis of new drugs, significantly improving reaction efficiency and reducing R&D costs.

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