Green Synthesis of Papaverine one of Opium Alkaloids in Water
نویسندگان
1 Soroush Mana Pharmed, Golrang Pharmaceutical Investment Co (GPI), Golrang Industrial Group (GIG), Tehran, Iran
2 Department of Chemistry, University of Zanjan, Zanjan (Iran)
3 Department of Molecular and Cell Biology, Faculty of Sciences, University of Mazandaran, Babolsar, Iran.
4 1-Department of organic chemistry, Faculty of chemistry, University of Mazandaran, Babolsar,47416-95447,Iran 2- Soroush Mana Pharmed, Golrang Pharmaceutical Investment Co (GPI), Golrang Industrial Group (GIG),Tehran, Iran
5 Department of organic chemistry, Faculty of chemistry, University of Mazandaran, Babolsar,47416-95447, Iran
6 Faculty of Chemistry and Petroleum Sciences, Department of Chemistry, Shahid Beheshti University, Tehran, Iran
7 Faculty of Chemistry and Petroleum Sciences, Department of Chemistry, Shahid Beheshti University, Tehran, Iran
doi
10.22036/org.chem.2024.432326.1309چکیده
Opium mixture serves as a vital source of alkaloids, including significant medicinal compounds used in the pharmaceutical industry. One such compound is papaverine (6), a benzylisoquinolinic alkaloid found in opium mixture, possessing distinct medicinal properties. This article addresses the limitations associated with extracting substances from natural compounds by focusing on the synthesis of papaverine in four comprehensive steps. The synthetic route employs 2-(4,3-dimethoxyphenyl) acetic acid (1), which undergoes transformation to yield methyl 2-(4,3-dimethoxyphenyl) acetate (2). Through the binding of compound (2) with commercially available 2-(4,3-dimethoxyphenyl) ethane amine (3), amide (4) is obtained. Subsequently, ring closure of compound (4) is efficiently achieved using polyphosphoric acid (PPA) in refluxing toluene, leading to the formation of 1-(4,3-dimethoxy-benzyl)-7,6-dimethoxy-4,3-dihydroisoquinoline (5). The next crucial step involves the hydrogenation of compound (5) with Pd/C in a water-solvent medium, successfully yielding the desired product, papaverine (6), with an impressive efficiency of 58.7%. Characterization of the formed products is carried out using FTIR, 1H NMR, 13C NMR, and Mass spectrometry techniques, confirming their chemical identities. By developing a synthetic approach to produce papaverine, this study offers valuable insights into the efficient synthesis of this important medicinal compound, potentially paving the way for its widespread application in the pharmaceutical industry.
