Enzyme-Mediated Hydrolysis of Poly(ethylene glycol)-Supported Carbonates

第44卷第5期复旦学报(自然科学版)Vol. 44 No.52005年10月Journal of Fudan University (Natural Science)Oct.2005Article D: 0427-7104(2005)05-0768-02Enzyme-Mediated Hydrolysis of Poly( ethyleneglycol)-Supported CarbonatesK. Matsumoto, M. Shimojo, M. Nogawa, M. Okudomi(Department of Chemistry, Meisei Uniersity, Hodokubo2-1- 1, Himo, Tokxo 191 - 8506, Japan)Keywords: enzymatic hydrolysis; optically active compounds; PEG; PPL; separation techniques; water-soluble polymersCLC number:Q 55Document code:A1 IntroductionEnzymatic kinetic resolution of racemic alcohols or esters is known as a useful method for the preparationof optically active secondary alcohols. However, the work- up including the separation of the mixture of the re-maining substrate and the resulting compound spend a lot of time and waste much amount of solvents. On theother hand, organic synthesis based on polymer supports has made rapid progress. Although the methodologyis potentially useful for the easy separation of compounds obtained by the enzymatic reaction, there have beenrelatively few reports on enzymatic resolutions of using a polymer so far. We have noticed that using a water-soluble polymer could be suitable for enzymatic transformation. Here, we report the first example of an en-zyme-mediated enantioselective hydrolysis of poly( ethylene glyol)(PEG)-supported substrates with a carbon-ate moiety to afford optically active compounds, and the method enables us to achieve the easy separation ofthe productsl1l. See Scheme 1.R2OEnzymeOHR!0-RI +R1*R2MPEGMw = 550, 750, and 5000Scheme 12 Results and DiscussionWe used three kinds of molecular weight monomethoxy PEG (MPEG, av Mw 550, 750 and 5 000) asthe supporting polymer because they had the desired solubility profile and the terminal methyl group is a g∞odreference for the NMR analysis. For a screening test, the polymer supported(士)-1 (Rl= Me, R2= 2-ben-zyloxyethyl, MPEG7so) was chosen as the substrate. After thgenzymes, porcine pancreas lipase (PPL, Type II from Sigma)MYH中国煤化工yme. The retionwas performed using 5 mmol/L of (+)-1 with PPL in0.1 mlCNMH G6.5). In this case,Received date: 2005-08-29Biography: K. Matsumoto,Correspondence author , e mail: mkazu@chem. meisei-u. ac. jp.第5期K. Matsumoto, et al :Enzyme mediated Hydrolysis of Poly( ethylene glyool) -supported Carbonates769(R)-1 was favorably hydrolyzed to afford the resulting alcohol (R)-2 and the remaining substrate (S)-1.The hydrolysisof (土)-1 at 30 C for 24 h was proceeded with good enantioselectivity, and the conversion andE value were 0. 29 and 23, respectivelyl21 . The suitable solubility of the MPEG-supported substrate enablesus to establish a facile separation of 1 and 2 (Scheme 2). In the first extraction step with hexane, only the al-cohol (R )-2 was selectively extracted into the hexane layer. In the following second extraction with AcOEt,(S)-1 was then sessfully obtained in the organic layer. Changing the support polymer to MPEGsso((土)-3) slightly improved the enantioselectivity. In the reactionof (土)-3at 10 C，the E value was up to 32.This procedure was able to apply the substrates bearing other substituents. It is noteworthy that using a morehigh-molecular weight MPEGsooo as the support polymer successfully causes the easier separation steps and im-proves the enantioselectivity.Hexane layerEthyI acetate layerWater layer个oBnOBnMe(R)-2COBn-oo” Me(S)-1o -OH)MPEGz50a,-OHMPEG7s0(a) Extraction with hexane(b) Extraction with ethyl acetateScheme 2References:[1] Shimojo M, Matsumoto K, Nogawa M, et al. Enzyme mediated enantioselective bydrolysis of poly( ethyleneglyol)- sprted carbonates[J]. Tetarahedrom Lett , 2004, 45: 6769-6773.[2] Chen C S, Fujimoto Y, Girdaukas G, et al. Quantitative analyses of biochemical kinetic resolutions of enan-tiomers[J].J Am Chem Soc, 1982, 104: 7294-7299.中国煤化工MYHCNMHG