考察了利用安大略假丝酵母(Candida ontarioensis)静息细胞不对称催化2-氯-1-(3-氯苯基)乙酮合成(R)-2-氯-1-(3-氯苯基)乙醇的转化反应条件.结果表明,当底物浓度为10g/L时,在最适转化条件下反应72 h,产物的ee值和产率分别达到99.9％和99.0％.采用4g/L十六烷基三甲基溴化铵对Candida ontarioensis细胞于4c通透性处理20 min后,全细胞的酶活提高2倍以上.当底物浓度提高为30g/L,转化24 h后,产物的ee和产率分别达到99.9％和97.5％.该研究为高效制备(R)-2-氯-1-(3-氯苯基)乙醇提供了可行途径,并为生物催化合成芳基手性醇类手性中间体提供了理论指导.
(R)-2-Chloro-l-(3-chlorophenyl)ethanol is a key pharmaceutical intermediate in the synthesis of β3-adrenoceptor receptor (β3-AR) agonists.The asymmetric reduction of 2-chloro- 1 -(3-chlorophenyl)ethanone to (R)-2-chloro- l-(3-chlorophenyl)ethanol catalyzed by resting cells of Candida ontarioensis was studied.At a substrate concentration of 10 g/L,the microbial cells showed excellent catalytic activity under the optimum reaction conditions,giving the product in 99.9％ ee and 99.0％ yield.After cetyltrimethylammonium bromide-pretreatment,the activity of permeabilized Candida ontarioensis cells was increased by more than 2-fold and the product could be produced over the significantly shortened reaction period of 24 h in 99.9％ ee and 97.5％ yield at a substrate concentration of 30 g/L.This work provides a practical approach for the efficient preparation of the important chiral intermediate (R)-2-chloro- l-(3-chlorophenyl)ethanol.
参考文献
| [1] | Kurbanoglu E B;Taskin M;Zilbeyaz K;Hasenekoglu I .[J].催化学报,2009,30:370. |
| [2] | Bloom J D;Dutia M D;Johnson B D;Wissner A Burns M G Largis E E Dolan J A Claus T H .[J].Journal of Medicinal Chemistry,1992,35:3081. |
| [3] | Ohkuma T;Tsutsumi K;Utsumi N;Arai N;Noyori R;Murata K .Asymmetric hydrogenation of alpha-chloro aromatic ketones catalyzed by eta(6)-arene/TsDPEN-ruthenium(II) complexes[J].Organic letters,2007(26):255-257. |
| [4] | Ni Y.;Xu JH. .Asymmetric reduction of aryl ketones with a new isolate Rhodotorula sp AS2.2241[J].Journal of molecular catalysis, B. Enzymatic,2002(4/6):233-241. |
| [5] | Schmid A;Dordick J S;Hauer B;Kiener A Wubbolts M Witholt B .[J].Nature,2001,409:258. |
| [6] | Woodley JM .New opportunities for biocatalysis: making pharmaceutical processes greener.[J].Trends in biotechnology,2008(6):321-327. |
| [7] | Tao, JH;Xu, JH .Biocatalysis in development of green pharmaceutical processes[J].Current opinion in chemical biology,2009(1):43-50. |
| [8] | 刘湘,方志杰,许建和.酵母细胞催化芳香酮的不对称还原反应[J].催化学报,2006(01):20-24. |
| [9] | de Carvalho C C .[J].Biotechnology Advances,2011,29:75. |
| [10] | Wohlgemuth P .[J].Current Opinion in Biotechnology,2010,13:283. |
| [11] | 马小魁,王喆之,陈五岭.酵母发酵液直接催化4-氯-乙酰乙酸乙酯不对称还原生成4-氯-3-羟基-丁酸乙酯[J].催化学报,2006(04):314-318. |
| [12] | Harada H;Hirokawa Y;Suzuki K;Hiyama Y;Oue M;Kawashima H;Yoshida N;Furutani Y;Kato S .Novel and potent human and rat beta(3)-Adrenergic receptor agonists containing substituted 3-indolylalkylamines.[J].Bioorganic and Medicinal Chemistry Letters,2003(7):1301-1305. |
| [13] | Sawa I;Konishi Y;Maemoto S;Hasegawa J .[P].EP 0493617A1,1992. |
| [14] | Lin H;Chen Y Z;Xu X Y;Xia S W Wang L X .[J].Journal of Molecular Catalysis B:Enzymatic,2009,57:1. |
| [15] | Itoh N;Matsuda M;Mabuchi M;Dairi T;Wang J .Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled with in situ regeneration of NADH.[J].European Journal of Biochemistry,2002(9):2394-2402. |
| [16] | Kizaki N;Yano M;Funaki M;Takesue T,Yasohara Y,Morikawa S,Nakai T,Kataoka M,Shimizu S .[P].US 7915022B2,2011. |
| [17] | Kizaki N;Sawa I;Yano M;Yasohara Y;Hasegawa J .Purification and characterization of a yeast carbonyl reductase for synthesis of optically active (R)-styrene oxide derivatives[J].Bioscience, Biotechnology, and Biochemistry,2005(1):79-86. |
| [18] | Shimizu S;Kataoka M;Kizaki N;Yasohara Y .[P].EP 1400594A1,2002. |
| [19] | Zhang B L;Pionnier S .[J].Chemistry-A European Journal,2003,9:3604. |
| [20] | Zhang W;Ni Y;Sun Z H;Zheng P Lin W Q Zhu P JuN F .[J].Process Biochemistry,2009,44:1270. |
| [21] | Ni Y;Chen R R .[J].Biotechnology and Bioengineering,2004,87:804. |
| [22] | Ni Y;Mao Z C;Chen R R .[J].Applied Microbiology and Biotechnology,2006,73:384. |
| [23] | He Y C;Zhang Z J;Xu J H;Liu Y Y .[J].Journal of Industrial Microbiology and Biotechnology,2010,37:741. |
| [24] | Yu M A;Wei Y M;Zhao L;Jiang L Zhu X B Qi W .[J].Journal of Industrial Microbiology and Biotechnology,2007,34:151. |
| [25] | Cortez D V;Roberto I C .[J].NewBiotechnol,2012,29:192. |
- 下载量()
- 访问量()
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%