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Technology Platform
Green Chemistry Technology Platform

Langhua Pharmaceutical always adheres to the concept of sustainable manufacturing, providing clients with green, low-carbon, and sustainable commercial production services. Leveraging its team advantages and project experience, Langhua has established a Green Chemistry Technology Platform. This platform integrates advanced synthesis technology methods such as biocatalysis, continuous flow process, metal catalysis, asymmetric catalysis, photochemistry and electrochemistry. By developing efficient, green, and competitive synthesis processes for active pharmaceutical ingredients (APIs) and intermediates with these above advanced technology, Langhua continuously creates value for its clients.

  • Enzymatic Synthesis Development Platform(or Biocatalysis Development Platform)

    Enzymatic synthesis, a biotransformation approach distinct from traditional chemical synthesis, has been widely used in the pharmaceutical industry due to its multifaceted advantages, including high efficiency, specificity, cost-effectiveness, and environmental friendliness. Langhua leverages Viva Biotech's exceptional strengths in protein structure analysis and design, and protein fermentation to establish an enzymatic synthesis platform. This platform offers clients services including high-throughput enzyme screening, directed evolution of enzymes, development and commercial production of enzymatic synthesis processes, quality control and regulatory submission of enzymatic synthesis processes.

    Enzyme Screening
    Preparation
    • Enzymes, NAD(P)H, NAD(P)+, GDH, Buffer (Ready in VIVA or Universities)
    • Substrate and products (Provided by clients)
    • Analysis methods for standard substrate and products. (Provided by clients)
    Reaction
    • High throughput and small volume reaction System
    • Convenient and requires short time
    Validation
    • Detection of product NAD(P)+ by absorption spectroscopy
    • Detection of products by UPLC, determine of stereoselectivity by HPLC
    Process Development
    Process Development
    Successful Applications

    The development of various enzymatic catalysis processes in CDMO orders have been successfully completed, involving esterases, ester hydrolases, ketone reductases (KRED), nitrile hydrolases (NIT), transaminase, lipases, chymotrypsin, acylase, oxidase ene reductase (ERED), olefin reductases, imine reductases, amino dehydrogenases, etc. An enzymatic synthesis process of a chiral ester has been developed with an esterase for an anti-COVID-19 drug project, of which the commercial production will be proceeded in the second half of the year.

    Case Studies
    KREDs
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    Ketoreductase screening for the asymmetric reduction of ketone compounds（The annual output of 30MT has been achieved）

    ATAs
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    Amine transaminase screening for the asymmetric reductive amination to produce chiral amines（It is expected to achieve an annual output of 20MT）

    Acylase
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    Acylase screening for the enantioselective hydrolysis of N-acetyl compounds（It is expected to achieve an annual output of 40MT）

    Recycling and Immobilized Enzyme
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    Recycling of the immobilized enzyme in enzymatic process (Retention efficiency of the immobilized enzyme after recycling three times )

  • Continuous Flow Process Development Platform

    Langhua Pharmaceutical's continuous flow process platform is equipped with a variety of modular equipment, including different kinds of pumps, gas or liquid mass flow controllers, (MFC), mixers, coil reactors made of stainless steel or PFA, microchannel reactors made of silicon carbide (SiC), packed bed reactors (PBR) , continuous stirred tank reactors (CSTR), back pressure valves (BPR), gas liquid separators (LGS), temperature control units (TCU), etc. Based on the process needs, those equipment could be flexibly assembled into a experiment apparatus for development and optimization of continuous flow process in lab. With automatic hydrogenator, Langhua could screen the catalysis and reaction conditions efficiently for hydrogenation. Additionally, the platform includes the commercial-scale microchannel continuous flow reactor with the production capacity of thousands of tons per annum, which could meet the larger-scale production needs.

     

    Langhua has successfully completed continuous flow process development for organolithium reaction, oxidation, diazotization, azide reaction, nitration, hydrogenation, etc, of which the apparatus flux capability could reach 1-50 kg per day. Langhua could provide service in the design of continuous process routes, continuous flow process development, reactor design, and the commercial production implementation of continuous flow process.

    Successful Applications
    • Developed continuous flow process for various hazardous reactions in CDMO orders, including ozonolysis, acylation, amination, diazo reaction, nitration, oxidation, and sulfonation.
    • Developed a continuous ozonolysis process for a GMP step of an innovative drug project.
    • Developed and implemented a two-step continuous flow process containing the acylation and amination for a commercial production project.
    Case Studies
    Ozonolysis
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    Diazotization
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    Bromination
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    Azide Reaction
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    Flux in lab: 20kg per day

    Organolithium Reaction
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    Flux in lab: 15kg per day

    Oxidation
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    Flux in lab: 30kg per day

    Hydrogenation
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  • Catalyst and Ligand Screening Platform

    Catalysts have been widely used in coupling reactions and asymmetric synthesis. To enhance the efficiency of route exploration and condition optimization, Langhua Pharmaceutical has established a catalyst and ligand screening platform. This platform offers services to clients, thereby saving time and cost in process development.

    Professional Teams & Facilities
    Professional Team
    Professional Team Professional Team

    A professional team of nearly 20 members, most of whom have studied in renowned research groups of metal or small molecule catalysis in China.

    Extensive Development Experiance
    Extensive Development Experiance Extensive Development Experiance

    Several core technical staff have over 10 years of research and development experience in the field of transition metal catalysis.

    The Catalyst and Ligand
    Screening Lab
    The Catalyst and Ligand <br>Screening Lab The Catalyst and Ligand <br>Screening Lab

    The Shanghai R&D center has a nearly 200 m² catalyst and ligand screening laboratory, equipped with glove boxes and high-throughput screening equipment.

    Catalyst or
    Auxiliary Library
    Catalyst or<br>Auxiliary Library Catalyst or<br>Auxiliary Library

    • Metal Catalyst and Ligand Library:

      Includes nearly 10 core metals and nearly 100 ligands.

    • Organocatalyst Library:

      Includes various kinds of chiral organocatalysts such as chiral prolines, cinchona alkaloids, chiral thioureas, and chiral phosphoric acids.

    • Chiral Auxiliary and Reagent Library:

      Includes natural chiral pool, Evans auxiliaries, chiral sulfonamides, etc.

    Successful Applications
    • Extensively used in CDMO order projects, involving metal-catalyzed coupling and asymmetric catalysis.
    • Multiple innovative drug projects during clinical phase II and III, where key steps involve catalytic process, have achieved production on tens of kilograms scale in plant.
    • Commercial production has been realized for metal-catalyzed coupling reactions such as Suzuki, Negishi, Heck, Kumada, Sonogashira, and Buchwald-Hartwig.
    Case Studies
    Suzuki Coupling
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    Heck Coupling
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    Buchwald-Hartwig Couplinig
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