Study On Synthesis Of ?-Alkynyl Tetrahydroisoquinoline Derivatives

Tetrahydroisoquinoline?THIQ?is a naturally widespread compounds.Many compounds which containing a tetrahydroisoquinoline skeleton have biological activities such as anti-inflammatory,anti-tumor and anti-pathogenic microorganisms,for example codeine,morphine,imitative and myostatin and other biologically active alkaloids.Natural products are difficult to meet people's needs because of restrictions on their origin,production,and intrinsic activities.Artificial synthetic method can be used to solve or improve this problem.Zimmermann introduced an alkynyl group at the?-position of the tetrahydroisoquinoline backbone of Noscapine and found that the modified compound had good anti-tumor biological activity and was less toxic than Noscapine.Research on the synthesis of?-alkynyltetrahydroisoquinolines has become a hot topic in the field of pharmaceuticals and has received more and more attention.This study aims to establish a new synthesis method of?-alkynyltetrahydroisoquinoline compounds for the synthesis of new compounds with medicinal value.The details are as follows:Optimizationofthesynthesisprocessof?-alkynyltetrahydroisoquinolines:N-acyltetrahydroisoquinoline and potassium alkynyltrifluoroborate were used as substrates.Through catalysts,solvents,and acyl protecting groups,an optimized synthesis process of oxytetrafluoroborate?TEMPO⁺BF₄^-?as catalyst,methylene chloride as solvent and benzyloxycarbonyl and tert-butylcarbonyl as N protecting groups was obtained.Applied research on optimized synthesis process:We synthesis 1²6 different types of?-alkynyl tetrahydroisoquinolines were synthesized and their productivity is high,yield range is 82⁹6%.In summary,we successfully optimized the synthesis of?-alkynyl tetrahydroisoquino-lines.The synthetic process has the following features:it has high efficiency and its reaction conditions are mild.