化学药实用工艺研究PracticalProcessResearchandDevelopment—冯鑫.pptxVIP

化学药实用工艺研究PracticalProcessResearchandDevelopment—冯鑫第1页/共43页 Content：1：Route Selection2: Reagent Selection3: Solvent Selection4: Running Reaction5: Optimizing the reaction by minimizing impurities6: Tools for Purifying the product 第2页/共43页 1 Route SlectionA Health, SAFETY, and Environmental assessment is a critical criterion in our process development....It’s got to be dealt with, and it’s not taken lightly. If problems are insurmountable, or If there is danger to the environment, a synthesis will be replaced.”第3页/共43页 1-1: Analyzing Waste Streams (First Principle)It is far better to prevent waste, not just reducing waste.第4页/共43页 Routes with fewer steps require smaller quantities of starting materials, solvents, and reagents, and require less labor.第5页/共43页 1-2: Atom EconomyAtom economy is not the primary consideration for manufacturing in the pharmaceutical industry1-3: Less Hazardous Chemical syntheses1-4: Reduce use of Protecting groupsThe route with the fewest steps may be the greenest and cheapest and the fewest opportunities for errors.-----difficult!!!!!1-5: CatalysisWith catalytic reactions involving expensive catalysts cost-efficient route will recycle the catalysts.1-6: Direct IsolationsDirect isolation minimize consumption of RM, energy, time and labor. And it is very convenient both for plant and Kilo-lab.Filtration/ crystallization/recrystallization/slurry is the favorite.第6页/共43页 Example 第7页/共43页 BiotransformationsBiotransformations provide exciting opportunities for changing synthetic routes.Previously fermentations were considered for complex molecules such as antibiotics.Biocatalysts have been developed for synthetic purposes and it was usually associated with enzymes: transaminases第8页/共43页 Example第9页/共43页 Example:第10页/共43页 Guidelines for developing biocatalytic processsQuickest to effectChange Example 1Screen mediumDissolve substrate in DMF, DMSO, or acetone2Modify starting materialChange Boc for benzyl3Screen biocatalystsHigh-throughp