caa a22 4500 46582269X CHVBK 20180323112140.0 cr unu---uuuuu 170327e19901001xx s 000 0 eng 10.1007/BF00170915 doi (NATIONALLICENCE)springer-10.1007/BF00170915 Stereoselective enzymatic hydrolysis of 2-cyclohexyl-and 2-phenyl-1,3-propanediol diacetate in biphasic systems [Elektronische Daten] [Ramesh Patel, Robert Robison, Laszlo Szarka] Summary: A key intermediate (S(−) 2-cyclohexyl-1,3-propanediol monoacetate) was made with high optical purity for the total synthesis of a new angiotensin converting enzyme inhibitor, Fosinopril. The stereoselective hydrolysis of 2-cyclohexyl-1,3-propanediol diacetate (I) and 2-phenyl-1,3-propanediol diacetate (II) was carried out with lipases. Among various lipases evaluated, only porcine pancreatic lipase (PPL) and Chromobacterium viscosum lipase demonstrated efficient conversion and gave the desired enantiomer of monoacetate. In aqueous solution, the desired S(−) monoacetate exhibited an optical purity of 65%-80% (30%-60% enantiomeric excess [e.e.]). However, when the same reactions were conducted in a biphasic system, the product S(−) monoacetate exhibited an optical purity of 99%-100% (98%-100% e.e.). The high purity product was achieved with 65 mol% yield at 1% substrate concentration. Among various solvents evaluated in biphasic systems, efficient hydrolysis was achieved in toluene, cyclohexane, and trichloro-trifluoroethane. The crude PPL was partially purified and two lipase fractions (A and B) were identified. Lipases A and B had a molecular mass of 38 000 and 40 000 daltons, respectively, and both were found to catalyze the hydrolysis of I and II to the appropriate monoacetate in a biphasic system. Springer-Verlag, 1990 Patel Ramesh Chemical Division, Bristol-Myers Squibb, Biological Process Research, 08903, New Brunswick, NJ, USA aut Robison Robert Chemical Division, Bristol-Myers Squibb, Biological Process Research, 08903, New Brunswick, NJ, USA aut Szarka Laszlo Chemical Division, Bristol-Myers Squibb, Biological Process Research, 08903, New Brunswick, NJ, USA aut Applied Microbiology and Biotechnology Springer-Verlag 34/1(1990-10-01), 10-14 0175-7598 34:1<10 1990 34 253 https://doi.org/10.1007/BF00170915 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00170915 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Patel Ramesh Chemical Division, Bristol-Myers Squibb, Biological Process Research, 08903, New Brunswick, NJ, USA aut NATIONALLICENCE 700 1- Robison Robert Chemical Division, Bristol-Myers Squibb, Biological Process Research, 08903, New Brunswick, NJ, USA aut NATIONALLICENCE 700 1- Szarka Laszlo Chemical Division, Bristol-Myers Squibb, Biological Process Research, 08903, New Brunswick, NJ, USA aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer-Verlag 34/1(1990-10-01), 10-14 0175-7598 34:1<10 1990 34 253 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer