Research On Tandem Cyclization Via Propargylic Alcohols And Bioactivities Of Triazolotetrahydro-β-carbolines

Objective:Synthesis of bioactive heterocyclic structures including triazolotetrahydro-β-carboline,pyrano[3,2-c]quinolone,furo[3,2-c]quinolone,cyclohepta[b]indole and furo[3,4-b]carbazole via Lewis or Br(?)nsted acid-catalyzed tandem cyclization of propargylic alcohols has good atom-and step-economy.Subsequently,minimal inhibitory concentration(MIC)of some triazolotetrahydro-β-carbolines were tested to study their bacteriostatic activity preliminarily.Methods:(1)Tandem cyclization of propargylic alcohols catalyzed by Lewis or Br(?)nsted acid catalyst.(2)According to the literature,the reaction system is optimized to select the best reaction conditions(catalyst,solvent etc).(3)The universality of the synthesis method with regard to the formation of the desired products under the optimized reaction conditions was verified.(4)The possible mechanism was proposed by isolation of the key intermediates and control experiments(5)The bacteriostatic activity of two triazolotetrahydro-β-carbolines against Escherichia coli was tested.Results:(1)A facile and efficient route to triazolotetrahydro-β-carboline from propargylic alcohols and 2-indolylmethyl azides via acid-catalyzed dehydrative annulation reactions was described.This reaction proceeds through a cascade sequence of Friedel–Crafts-type alkylation followed by intramolecular “Click” reaction,involving the formation of multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.(2)Two acid-catalyzed tandem reactions between propargylic alcohols and 4-hydroxy-1-methylquinolin-2(1H)-one were described.Depending mainly on the propargylic alcohol used,these tandem reactions proceed via either a Friedel–Crafts-type allenylation followed by 6-endo-trig cyclization sequence to form pyrano[3,2-c]quinolones or a Friedel–Crafts-type alkylation and 5-exo-dig ring closure sequence to afford furo[3,2-c]quinolones in moderate-to-high yields.Furthermore,The pyrano[3,2-c]quinolones products could be further transformed to novel tetracyclic quinolone derivatives.(3)A robust metal-free and environment-friendly approach for the construction of cyclohepta[b]indoles and furo[3,4-b]carbazoles frameworks by substrate(indole)-controlled strategy with cheap and easily available starting materials(indoles,tertiary propargylic alcohols and activated alkynes)was described,which was performed under mild conditions to obtain diversely functionalized target products.A probable mechanism was proposed based on the ioslation and characterization of the key intermediate.A gramscale reaction and further transformations were also performed to demonstrate the practical applicability of the developed methodology.(5)The triazolotetrahydro-β-carboline compound 3aa had significant bacteriostatic effects on Escherichia coli.Conclusion:(1)In this paper,bioactive heterocyclic structures including triazolotetrahydro-β-carboline,pyrano[3,2-c]quinolone,furo[3,2-c]quinolone,cyclohepta[b]indole and furo[3,4-b]carbazole were synthesized by Lewis or Br(?)nsted acid-catalyzed tandem cyclization of propargylic alcohols and the possible reaction mechanisms were proposed(2)The bioactivity of triazolotetrahydro-β-carboline compounds were briefly investigated by the minimal inhibitory test.