Large scale preparation of chiral building blocks for the P3 site of renin inhibitors
| Autor: | Wolfgang Wostl, Ernst Kupfer, Thomas Weisbrod, Beat Wirz, Stephan Doswald, Willi Walther, Heinz Stadler, Heinrich Estermann |
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| Rok vydání: | 1994 |
| Předmět: |
Magnetic Resonance Spectroscopy
Optical Rotation Morpholines Clinical Biochemistry Pharmaceutical Science Biochemistry Hydrolysis Renin Drug Discovery Organic chemistry Subtilisins Molecular Biology Separator (electricity) chemistry.chemical_classification Sulfonyl Phenylpropionates Angiotensin II Organic Chemistry Substrate (chemistry) Esters Stereoisomerism Kinetics Enzyme chemistry Emulsion Propionate Thermodynamics Molecular Medicine Emulsions Indicators and Reagents Selectivity |
| Zdroj: | Bioorganic & Medicinal Chemistry. 2:403-410 |
| ISSN: | 0968-0896 |
| Popis: | Racemic ethyl 2-benzyl-3-(tert-butylsulfonyl)propionate (1) and racemic ethyl 2-benzyl-3-[[1-methyl-1-((morpholm-4-yl)carbonyl)ethyl]sulfonyl]p (3) were enantioselectively hydrolyzed by subtilisin Carlsberg generating the respective (S)-acids used as building blocks for renin inhibitors. The esters were readily converted as emulsions at elevated temperature, in a suspended form or a two-phase-liquid system. The enzyme maintained its excellent selectivity and a good activity also at high initial substrate concentrations (up to 50 % w/w). The enzymatic reaction and work-up were optimized and scaled up. Emulsion problems during work-up encountered with these highly concentrated mixtures were solved by application of a disk separator for phase separation. |
| Databáze: | OpenAIRE |
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