Review Article
Austin J Anal Pharm Chem. 2015;2(1): 1033.
Research on Phase Transfer Catalytic Reactions and their Application in Drug Synthesis
Ziyu Wang, Xueyan Zhang, Pei Xu, Daorui Huang, Xiaolong Wang and Zhenya Dai*
Department of Pharmaceutical Chemistry, School of Pharmacy, China Pharmaceutical University, China
*Corresponding author: Dai Zhenya, Department of Pharmaceutical Chemistry, School of Pharmacy, China Pharmaceutical University, China.
Received: February 14, 2015; Accepted: February 12, 2015; Published: March 02, 2015;
Abstract
Our recent work was reviewed herein and our future work was also planned herein. Herein our achievements in the investigation on the phase transfer catalytic reactions were reported, and our future plan on the phase transfer catalytic reactions were also reported.
Keywords: Phase transfer catalysis; Asymmetric phase transfer catalysis; Drug synthesis; Synthesis of chiral drugs
Introduction
Phase transfer catalysis is of great importance in organic synthesis of drug synthesis [1]. The study of phase transfer catalytic reaction and their application in drug synthesis was focused by our group. Herein our work on the phase transfer catalytic reactions was reviewed.
A number of new phase transfer catalytic reactions were investigated and were applied in drug synthesis. For example, the Darzens reaction between aldehydes and chloroacenitrile (Figure 1) was accomplished and then applied in the synthesis of diltiazem. Similarly the Darzen reactions between aldehyde and t-butyl chloroacetate was performed and then applied in the synthesis of diltiazem (Figure 1) by our research group [2a, 2b].
Figure 1: Phase transfer catalytic Darzens reaction.
Also, the phase transfer catalytic reactions were applied in the synthesis of drug intermediate of vernakalant, which was more convenient and more easily handled than the traditional routine [3] (Figure 2).
Figure 2: Synthesis of vernakalant.
Further, the phase transfer catalytic reactions were also applied in the synthesis of firocoxib and etoricoxib (Figure 3), which was now in preparation of patent.
Figure 3: Synthesis of firocoxib and etoricoxib.
Based on the study above, we also turned our attention to asymmetric phase transfer catalytic reactions; several new chiral phase transfer catalysts were designed and synthesized in our study. For example, the cyclic chiral phase transfer catalysts were designed and synthesized by treating cinchona with 2-bromo- 1-(4-(trifluoromethyl) phenyl) ethan-1-one(catalyst 1-4), and the new catalysts were applied in the asymmetric alkylation and asymmetric sulfenylation of glycine derivative with moderate to high enantioselectivity (Figure 4) [4, 5].
Figure 4: synthesis of the new chiral phase transfer catalysts and their
application in asymmetric alkylation and sulfenylation of glycine derivative.
A new type of chiral phase transfer catalysts was designed and synthesized by treating cinchona with 1, 4-dibromobut-2-ene(catalyst 5-8), and they were also applied in the asymmetric alkylation of glycine derivative with moderate to excellent enantioselectivity (Figure 5) [6].
Figure 5: Synthesis of new chiral phase transfer catalysts and their
application in asymmetric alkylation of glycine derivative.
The new type of chiral phase transfer catalysts were furtherapplied in other asymmetric reactions, such as asymmetric Darzens reaction, with moderate to high diastereos electivity and moderate enantioselectivity, which also was applied in the synthesis of diltiazem (Figure 6) [7].
Figure 6: Application of new chiral phase transfer catalysts in asymmetric
Darzens reaction.
In continuation of our study on the phase transfer catalysis, we will try to find some new type of phase transfer catalytic reactions and try to apply them in the drug synthesis. In another aspect, we will also try to design some new type of chiral phase transfer catalysts and apply them in the classical and new type of phase transfer catalytic reactions, and we will also try to apply them in the synthesis of chiral drug or chiral drug intermediates.
Acknowledgement
We were thankful to the National Natural Science Foundation of China for their financial support (No. 21102180).
References
- Hashimoto T, Maruoka K. Recent development and application of chiral phase-transfer catalysts. Chem Rev. 2007; 107: 5656-5682.
- (a)Li CS, Wang YC, Yu JJ, Dai ZY*, You QD*, Wang DF. Optimzation of the synthesis of the intermediate of diltiazem. Pharmaceutical and Clinical Research 2011, 19, 184-185.
- (b)Wang YC, Wang BC, Yuan FP, Yu JJ, Dai ZY*, You QD*. Synthesis of the intermediate of diltiazem. Pharmaceutical and Clinical Research 2011, 19, 470.
- Dai ZY, Yuan FP, Zhao JH, Wang YC, Li CS, Zhao YD. One method of the preparation of R-4-benzyloxylpyrrolidine. CN201210085627.2
- Dong XY, Wang ZY, Huang DR, Xu P, Dai ZY*. Synthesis of New Chiral Phase Transfer Catalysts and their Application in the Asymmetric Alkylation of Glycine Derivatives. Austin J Anal Pharm Chem. 2014, 1(1), 3.
- Dong X, Xu P, Wang Z, Huang DR, Dai ZY*. Asymmetric Sulfenylation of Glycine Derivative Catalyzed by the Novel Chiral Phase Transfer Catalysts. Austin J Anal Pharm Chem. 2015, 2(1), 1032.
- Wang ZY, Huang DR, Xu P, Dong XY, Wang XL, Dai ZY*. The asymmetric alkylation reaction of glycine derivatives catalyzed by the novel chiral phase transfer catalysts. Tetrahedron Lett. In press.
- Wang ZY, Xu P, Huang DR, Dong XY, Wang XL, Dai ZY*. The asymmetric Darzens reaction catalyzed by the novel chiral phase transfer catalysts derived from cinchona alkaloids. Submitted to Tetrahedron Lett. In revision.
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