简介
1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸是近年来发展较快的一种新型饲料添加剂，属于酸化剂的一种。添加到动物饲料中具有降低肠道pH、调节肠道微生态平衡、提高饲料营养物质的消化和吸收等功能[1-2]。另有研究报道，1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸能通过微生物细胞膜，在其细胞内分解产生H+，降低或抑制细胞内酶的活性，破坏微生物蛋白和核酸的营养代谢，从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]二氧杂环戊烯-5-基)环丙烷甲酸盐阴离子在细胞壁外分解细菌细胞壁蛋白质，发挥杀菌和抑菌作用[5]。1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸的抗菌作用减少了微生物的数量，尤其是大肠杆菌等致病菌的数量，减少了微生物代谢物的产生，从而减少了对肠道的损害[6]。
图1 1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸的结构式。
合成
图2 1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸的合成路线[7]。
将化合物19(1当量)的DMSO溶液(1.25卷)添加到NaCN(1.4当量)的DMSO溶液中，保持温度在30-40℃之间。混合物搅拌1小时，然后加入水，然后加入MTBE。搅拌30分钟后，层分离。水层用MTBE提取。结合的有机层用水洗涤，干燥(Na2SO4)，过滤和浓缩，以获得直接用于下一步的粗化合物20(95%)。产量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℃下加热1 h。将反应混合物冷却，然后与MTBE和水混合。有机相用水和盐水洗涤，然后除去溶剂，得到化合物21。产量100%。最后化合物21用6 M NaOH(8等当量)在乙醇(5卷)中在80°C水解。过夜。混合物冷却到室温，乙醇在真空下蒸发。将残渣放入水和MTBE中，加入1 M HCl，层分离。然后用二环己胺(0.97当量)处理MTBE层。料浆冷却至0°C。，用庚烷过滤洗涤，得到相应的DCHA盐。将盐放入MTBE和10%柠檬酸中搅拌，直到所有固体溶解。将层分离，用水和盐水冲洗MTBE层。溶剂交换到庚烷，然后过滤，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]二氧杂环戊烯-5-基)环丙烷甲酸。产量69%。合成路线如图2所示。
图3 1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸的合成路线[8]。
在80°C下，用6 M NaOH（8当量）在乙醇（5体积）中水解化合物21。在夜间将混合物冷却至室温，并在真空下蒸发乙醇。将残留物放入水中，加入MTBE、1M HCl并分离各层。然后用二环己胺（0.97当量）处理MTBE层。将浆料冷却至0°C。，过滤并用庚烷洗涤，得到相应的DCHA盐。将盐放入MTBE和10%柠檬酸中，搅拌直至所有固体溶解。分离各层，用水和盐水洗涤MTBE层。在50°C的真空烘箱中干燥后，溶剂交换为庚烷，然后过滤得到化合物1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸。收率69%。合成路线如图3所示。
应用
许多研究表明在仔猪饲粮中添加1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸能改善仔猪的日增重，提高饲料转化效率[9]。研究表明，在仔猪饲粮中添加1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸1%与对照组比日增提高7.1%，料肉比降低13.71%，稍影响采食量[10]。在生长仔猪饲粮中添加 1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸1.8%，日增重提高8%～18%。1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸在家禽方面的应用报道较少[11]。有研究者在肉仔鸡饲粮中添不同水平的1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸，能显著增加肉仔鸡的采食量，提高饲粮的表观消化率和氮的沉积，日增重也有上升的趋势。添加量为0.6%时效果最明显，采食量和日增重分别提高了8.7%和5.8%，但饲料转化率差异不显著[12-13]。
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