synthesis and contractile activity of substituted 1,2,3,4-tetrahydroisoquinolines合成和收缩活动取代的1、2、3 4-tetrahydroisoquinolines.pdfVIP

Molecules 2011, 16, 7019-7042; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Contractile Activity of Substituted 1,2,3,4-Tetrahydroisoquinolines Iliyan Ivanov 1,*, Stoyanka Nikolova 1, Dimo Aladjov 1, Iliyana Stefanova 2 and Plamen Zagorchev 2,* 1 Department of Organic Chemistry, University of Plovdiv, 24 Tzar Assen Street, 4000 Plovdiv, Bulgaria 2 Department of Biophysics, Medical University, 15A Vasil Aprilov Street, 4000 Plovdiv, Bulgaria * Authors to whom correspondence should be addressed; E-Mails: ivanov@uni-plovdiv.bg (I.I.); plamenz@gbg.bg (P.Z.); Tel.: +359-32-261-349; Fax: +359-32-261-403. Received: 22 July 2011; in revised form: 10 August 2011 / Accepted: 11 August 2011 / Published: 16 August 2011 Abstract: A series of different 1-monosubstituted and 1,1-disubstituted 1,2,3,4-tetrahydro- isoquinolines was synthesized in high yields from different ketoamides. We have developed a convenient method for the synthesis of disubstituted derivatives by interaction of ketoamides with organomagnesium compounds, followed by cyclization in the presence of catalytic amounts of p -toluenesulfonic acid (PTSA). A number of substituents at the C-1 in the isoquinoline skeleton were introduced varying either carboxylic acid or organomagnesium compound. Some of the obtained 1,1-dialkyl-1,2,3,4-tetrahydro- isoquinolines possess contractile activity against guinea pig’s gastric smooth muscle