面包酵母作為生物催化劑還原潛手性的酮構(gòu)建手性中心的反應(yīng)，近幾年在有機合成中得到廣泛的應(yīng)用。最初面包酵母的應(yīng)用是1898年將糠醛還原為糠醇，之后經(jīng)Macleod和Hub的研究拓寬了這一反應(yīng)的應(yīng)用。近幾十年對于此反應(yīng)在水相進而在有機相中反應(yīng)取得進展，越來越多的有機合成化學家考慮應(yīng)用酵母還原反應(yīng)底物制備重要的手性醫(yī)藥中間體。
酵母還原有以下特點：高度專一的立體選擇性；反應(yīng)溫和反應(yīng)速率快；還原反應(yīng)收率高，成本低；符合綠色化學要求，環(huán)境友好。
反應(yīng)應(yīng)用
合成芬氟拉明的重要中間體(J. Org. Chem. 1991,56,6019)：
托莫西汀類似物的手性中心構(gòu)建(Indian J. Chem. 1992,31B, 803)：
j酵母還原 Ethyl Acetoacetate: (S)-( + )-Ethyl 3-Hydroxybutanoate ( Organic Syntheses, Coll.Vol. 7, p.215; Vol. 63, p.1):
A 4-L,three-necked, round-bottomed flask equipped with mechanicalstirrer, bubble counter, and a stopper is charged with 1.6 L of tap water, 300 g of sucrose,and 200 g of baker's yeast, which are added with stirring in this order. Themixture is stirred for 1 hr at about 30°C, 20.0 g (0.154mol) of ethylacetoacetate is added, and the fermenting suspension is stirred for another 24 hr at roomtemperature. A warm (ca. 40°C) solution of 200 g of sucrose in 1 Lof tap water is then added, followed 1 hr later by an additional 20.0 g (0.154 mol) of ethylacetoacetate. Stirring is continued for 50–60 hr at roomtemperature. When the reaction is complete by gas chromatographic analysis, themixture is worked up by first adding 80 g of Celite and filtering through a sintered-glass funnel (porosity 4, 17-cm diam). Afterthe filtrate is washed with 200 mL of water, it is saturated with sodium chloride and extracted with five 500-mL portions of ethylether. The combined etherextracts are dried over magnesiumsulfate, filtered, and concentrated with a rotaryevaporator at 35°C bath temperature to a volume of 50–80 mL. Thisresidue is fractionally distilled at a pressure of 12 mm through a 10-cm Vigreux column, and the fraction boiling at 71–73°C (12 mm) is collected to give 24–31 g (59–76%) of (S)-( + )-ethyl 3-hydroxybutanoate; thespecific rotation [α]25D + 37.2° (chloroform,c 1.3) corresponds to an enantiomeric excess of 85%.
The enantiomeric excessmay be enhanced by several crystallizations of the 3,5-dinitrobenzoatederivative or else by using "starved" yeast.
