簡(jiǎn)介

1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸是近年來發(fā)展較快的一種新型飼料添加劑，屬于酸化劑的一種。添加到動(dòng)物飼料中具有降低腸道pH、調(diào)節(jié)腸道微生態(tài)平衡、提高飼料營(yíng)養(yǎng)物質(zhì)的消化和吸收等功能[1-2]。另有研究報(bào)道，1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸能通過微生物細(xì)胞膜，在其細(xì)胞內(nèi)分解產(chǎn)生H+，降低或抑制細(xì)胞內(nèi)酶的活性，破壞微生物蛋白和核酸的營(yíng)養(yǎng)代謝，從而使微生物不能繁殖，甚至死亡[3-4]。1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸鹽陰離子在細(xì)胞壁外分解細(xì)菌細(xì)胞壁蛋白質(zhì)，發(fā)揮殺菌和抑菌作用[5]。1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸的抗菌作用減少了微生物的數(shù)量，尤其是大腸桿菌等致病菌的數(shù)量，減少了微生物代謝物的產(chǎn)生，從而減少了對(duì)腸道的損害[6]。

圖1 1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸的結(jié)構(gòu)式。

合成

圖2 1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸的合成路線[7]。

將化合物19(1當(dāng)量)的DMSO溶液(1.25卷)添加到NaCN(1.4當(dāng)量)的DMSO溶液中，保持溫度在30-40℃之間?；旌衔飻嚢?小時(shí)，然后加入水，然后加入MTBE。攪拌30分鐘后，層分離。水層用MTBE提取。結(jié)合的有機(jī)層用水洗滌，干燥(Na2SO4)，過濾和濃縮，以獲得直接用于下一步的粗化合物20(95%)。產(chǎn)量100%。然后化合物20 (1.0 eq)、50 wt % KOH水溶液(5.0 eq) 1-溴-2-氯乙烷(1.5 eq)和Oct4NBr (0.02 eq)的混合物在70℃下加熱1 h。將反應(yīng)混合物冷卻，然后與MTBE和水混合。有機(jī)相用水和鹽水洗滌，然后除去溶劑，得到化合物21。產(chǎn)量100%。最后化合物21用6 M NaOH(8等當(dāng)量)在乙醇(5卷)中在80°C水解。過夜?；旌衔锢鋮s到室溫，乙醇在真空下蒸發(fā)。將殘?jiān)湃胨蚆TBE中，加入1 M HCl，層分離。然后用二環(huán)己胺(0.97當(dāng)量)處理MTBE層。料漿冷卻至0°C。，用庚烷過濾洗滌，得到相應(yīng)的DCHA鹽。將鹽放入MTBE和10%檸檬酸中攪拌，直到所有固體溶解。將層分離，用水和鹽水沖洗MTBE層。溶劑交換到庚烷，然后過濾，在真空烘箱中50°C干燥后得到化合物1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸。產(chǎn)量69%。合成路線如圖2所示。

圖3 1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸的合成路線[8]。

在80°C下，用6 M NaOH（8當(dāng)量）在乙醇（5體積）中水解化合物21。在夜間將混合物冷卻至室溫，并在真空下蒸發(fā)乙醇。將殘留物放入水中，加入MTBE、1M HCl并分離各層。然后用二環(huán)己胺（0.97當(dāng)量）處理MTBE層。將漿料冷卻至0°C。，過濾并用庚烷洗滌，得到相應(yīng)的DCHA鹽。將鹽放入MTBE和10%檸檬酸中，攪拌直至所有固體溶解。分離各層，用水和鹽水洗滌MTBE層。在50°C的真空烘箱中干燥后，溶劑交換為庚烷，然后過濾得到化合物1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸。收率69%。合成路線如圖3所示。

應(yīng)用

許多研究表明在仔豬飼糧中添加1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸能改善仔豬的日增重，提高飼料轉(zhuǎn)化效率[9]。研究表明，在仔豬飼糧中添加1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸1%與對(duì)照組比日增提高7.1%，料肉比降低13.71%，稍影響采食量[10]。在生長(zhǎng)仔豬飼糧中添加 1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸1.8%，日增重提高8%～18%。1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸在家禽方面的應(yīng)用報(bào)道較少[11]。有研究者在肉仔雞飼糧中添不同水平的1-(2,2-二氟苯并[D][1,3]二氧雜環(huán)戊烯-5-基)環(huán)丙烷甲酸，能顯著增加肉仔雞的采食量，提高飼糧的表觀消化率和氮的沉積，日增重也有上升的趨勢(shì)。添加量為0.6%時(shí)效果最明顯，采食量和日增重分別提高了8.7%和5.8%，但飼料轉(zhuǎn)化率差異不顯著[12-13]。

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