Synthesis And Antimicrobial Activity Of Calycanthaceous Alkaloids Analogues

Calycanthaceous alkaloids,which contains calycanthine,folicantihine,chimonanthine and calycanthidine,are an important class of alkaloid plant natural products that can be isolated from the root,leaves,flower,and fruit of chimonanthus praecox.They possess a unique chiral,dimeric core structure.Calycanthaceous alkaloids have demonstrated important biological activities against plant pathogenic fungi.We investigate the structure dependence of biological activities in different Calycanthaceous alkaloids analogues,which is of interest to the development of novel,biorational pesticides.Tryptophan was used as starting material to synthesize the calycanthaceous alkaloids core structure tetrahydropyrroloindole,from which a series of derivatives were synthesized.The biological activities of these compounds towards a wide variety of bacteria and plant pathogen fungi were evaluated,with the following results:(1)Synthetic route:Calycanthaceous alkaloids core structure tetraahydropyrroloindole was synthesized from tryptophan starting material through a series of reactions.Calycanthaceous alkaloids analogues were synthesized by acylation and alkylation reactions at the 8-N position.Acylation reactions resulted in 24 derivative compounds,21 of which have not been previously characterized.Alkylation reactions resulted in unexpected ring opening of the folicanthine core structure at the C-N bond;21 tryptophan methyl ester derivatives were synthesized,20 of which have not been previously characterized.The synthesized compounds were characterized by 1H-NMR,13C-NMR?DEPT(90� and 1350).(2)Disk diffusion antibiotic testing was utilized,with streptomycin sulfate as a positive control,to evaluate the biological activities of all 45 synthesized calycanthine derivatives against Bacillus cereus,Staphylococcus aureus,Bacillus subtilis,Pseudomonas aeruginosa,Escherichia coli,and Ralstonia solanacearum.Of the compounds tested,LL-2-3,LL 2-4,LL-2-20 exhibited a high degree of activity towards Gram positive Bacillus subtilis;LL-1-14,LL-1-18 exhibited a high degree of activity towards Ralstonia solanacearum.(3)Spore germination inhibition assay was utilized,with 80%(v/v)mancozeb as a positive control,to evaluate the biological activities of all 45 synthesized calycanthine derivatives against Curvularia lunata,Botrytis cinerea at concentrations less than 100 ?g mL-1.Compound LL-1-9 exhibited a high degree of activity against Curvularia lunata,with 90.96%activity at a concentration of 100 ?g ml-1 and EC50 = 44.63 ?g mL-1.(4)Mycelium growth inhibition assay was utilized,with carbendazim as a positive control,to evaluate the biological activities of all 45 synthesized folicanthine danalogues against Eggplant Verticillium,Fusarium oxysporum,Colletrotrichum gloesporioides,Botrytis cinerea,Alternaria alternate,Gibberella zeae,Sclerotinia sclerotiorum,Curvularia lunata at concentrations less than 100 ?g mL-1.Among the synthesized compounds,LL-1-7,LL-1-8,LL-1-13,and LL-1-17 exhibited high degrees of activity against Sclerotinia sclerotiorum,with LL-1-8 being the most effective with an EC50 of 38.41 ?g mL-1.Compound LL-1-9 exhibited activity against Botrytis cinerea,with an EC50 of 79.52 ?g mL-1.Compounds LL-2-19 and LL-2-21 exhibited activity against Fusarium oxysporum,and compound LL-2-21 exhibited activity against Fusarium oxysporum and Eggplant Verticillium,with EC50 values of 58.27 ?g mL-1 and 77.39 g? mL-1,respectively.