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Biocatalytic Aerobic Oxidation for Islatravir

有机合成与工艺文献分享 2025-04-22 08:39
文章摘要
本文介绍了默克公司在开发伊斯拉曲韦生物催化级联反应中的酶促有氧氧化过程。研究通过改变氧化和磷酸化的反应顺序，并利用蛋白质工程和酶表达优化技术，提高了半乳糖氧化酶变体对三醇4的活性和选择性。研究发现，对酶成熟和催化机制的深入理解对反应开发至关重要。同时，通过酶固定化技术解决了高蛋白负荷问题，实现了首次公斤级工厂示范。此外，研究还通过严格表征不同规模的体积传质系数(kLa)和调节影响氧传质热力学的工艺参数，解决了大规模生产中氧高效输送的挑战。最终，通过采用高压和低温条件，在最小化制造设备改造投资的情况下，实现了酶效率的最大化。
Biocatalytic Aerobic Oxidation for Islatravir
查看文献： Development of a Biocatalytic Aerobic Oxidation for the Manufacturing Route to Islatravir
查看期刊：Organic Process Research & Development
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