顺/反-异戊烯基-3-甲基丁二烯醚的合成研究

以异戊烯醛和异戊烯醇为原料,经异戊烯酸催化缩醛化反应得到3-甲基-2-丁烯醛二异戊烯基缩醛,再经磷酸催化消除反应得到顺/反-异戊烯基-3-甲基丁二烯醚。对缩醛化反应条件和消除反应条件等工艺条件进行了详细研究。结果表明,以0.3%异戊烯酸为酸性催化剂,70~75℃共沸脱水反应8 h,异戊烯醛的单程转化率达到63%~64%,处理后可得含量为97.5%的3-甲基-2-丁烯醛二异戊烯基缩醛,收率96.8%;以100×10-6磷酸为催化剂,90~120℃,2.66 kPa下反应并及时将反应产物蒸出,处理后得到含量为95.7%的顺/反-异戊烯基-3-甲基丁二烯醚,收率97.0%。

柠檬醛及中间体的合成

以异戊烯醛和异戊烯醇为原料,经异戊烯酸催化缩醛化反应得到3-甲基-2-丁烯醛二异戊烯基缩醛,再经磷酸二氢铵催化消除反应得到顺/反-异戊二烯基-3-甲基丁二烯醚,并进一步热重排获得柠檬醛。研究了缩醛化反应条件和消除反应条件对转化率的影响。结果表明,以0.3%异戊烯酸为酸性催化剂,70～75℃共沸脱水反应8 h,异戊烯醛的单程转化率达到63%～64%,处理后可得含量为97.5%的3-甲基-2-丁烯醛二异戊烯基缩醛,收率96.8%;以0.2%～0.5%磷酸二氢铵为催化剂,100～130℃,2.66 kPa下反应并及时将反应产物蒸出,处理后得到含量为95.9%的顺/反-异戊二烯基-3-甲基丁二烯醚,收率97.0%。顺/反-异戊二烯基-3-甲基丁二烯醚在120～130℃重排反应1 h,其反应产物柠檬醛含量97.5%,收率90.2%。

Determination of 8,2′-diprenylquercetin 3-methyl ether in plasma by UPLC-MS-MS and its pharmacokinetic application in rats

8,2＇-Diprenylquercetin 3-methyl ether with significant anti-breast cancer activity is the main constituent of Tibetan medicine Sinopodophylli Fructus. In the present study, we developed and validated a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the determination of 8,2＇-diprenylquercetin 3-methyl ether in rat plasma. 8-Prenylkaempferol was used as the internal standard. The separation was carried out using Waters ACQUITY UPLC BEH C18 column （2.1 mm×100 ram, 1.7 μm） with a mobile phase consisting of acetonitrile and 0.1% formic acid in water on a gradient program at a flow rate of 0.4 mL＇min-1 and temperature of 30 ℃. Triple quadrupole mass spectrometric detection in negative ion mode was used for multiple-reaction monitoring of the transitions at m/z 451.30→177.25 and m/z 353.25→298.15 for 8,2＇-diprenylquercetin 3-methyl ether and 8-prenylkaempferol, respectively. The calibration curves were linear within the concentration range 0.1-2000 ng/mL （r = 0.9954）. The recoveries were 103%-115%, and the results were consistent across low, middle and high concentration levels. The intra- and inter-day precisions were within 15%, and the bias was between --6%-15%. This method was simple, rapid and sensitive, which could be applied to the determination of 8,2＇-diprenylquercetin 3-methyl ether in plasma and pharmacokinetic study in rats. Pharmacokinetic test indicated that the peak plasma concentration occurred in 2 h after the female rats were intragastrically administered with 8,2＇-diprenylquercetin 3-methyl ether at the dose of 100 mg/kg, and the biological half-life was 6.79 h. The blood drug concentration maintained equal amount for 20 h, which was conducive to the in vivo effects of drugs.

双马来酰亚胺树脂增韧改性剂的合成

经两步反应合成了二苯甲烷型双马树脂(BDM)的改性剂二(2-氯代-3-羟丙基醚)二烯丙基双酚A,测定了产物粘度并以红外光谱和核磁谱图对其结构进行了表征。通过环氧值和产率测定研究了催化剂对反应的影响,结果表明,第一步反应中可以Na OH颗粒为催化剂和缚酸剂,第二步反应中缩水甘油醚化二烯丙基双酚A可在稀盐酸条件下进行开环反应。加入该改性剂后,BDM在环氧树脂中的添加质量分数可达到30%以上。