Study On Asymmetric Synthesis Of Spiro-[Piperidine-2,3’-Quinoline]-2’-One

Quinoline compound is a kind of important pharmaceutical intermediates. As the mother nucleus,2-(1H)-quinoline derivatives have the antitumor, antianxiety, d-iminishing inflammation, hypertensive, antipyretic and analgesic pharmacological a-ctivities effects. As the structure of a special kind of quinoline, chiral quinoline spiro-compounds are rarely reported in the field of medicine synthesis. This topic designed and synthesized (R)-sprio[piperidine-2,3’-quinoline]-2’-one,which had the great significance for the further study of chiral quinoline spiro-compounds applic-ation value.This article designed three synthetic routes of spiro-[piperidine-2,3’-quinoline]-2’-one through the synthesis of chiral analysis method. Route one, which adopted the method of memory of chirality and use (L)-2-phenyl glycine as raw material. Due to the lack of chiral memory, the racemic product was obtained in the alk-ylation reaction. Route two, which also adopted the method of memory of chirali-ty, use (L)-2-methyl nitrobenzene alanine as raw material, the e.e. value of the p-roduct was only32%. Route three, which adopted the method of asymmetric syn-thesis, obtained (R)-spiro[piperidine-2,3’-quinoline]-2’-one after a series of asymme-tric induction reaction.In the research process, the reduction process of phenyl glycine was optimi-zed, kept the original yield, simplified the experimental steps. In N-alkylation rea-ction of R-2, the better reaction conditions were determined:acetonitrile as solve-nt, triethylamine as base, yield is above70%; In C-alkylation reaction of R-7, K-HMDS as base, THF and HMPA as solvent, the expected configuration of carbon atom was obtained; Friedel-crafts alkylation reaction was adopted in the cyclizati-on reaction; Beckmann rearrangement reaction was adopted in the rearrangement reaction., which to maintain the original chirality of carbon atom. This paper got a general method of synthesis chiral spiro-quinoline compounds by asymmetric s-ynthesis, which had great significance on deeper research of the activity of these compounds.