Synthesis And Antibacterial Activity Of Half-calycanthaceous Alkaloids Analogues

Calycanthaceous alkaloids are an important class of indole alkaloids that can be isolated from the root,leaves,flower,and fruit of chimonanthus praecox.They possess a unique chiral,dimeric core structure.They are made pyrroloindole tricyclic ring system formed by dimerization.The pyrroloindoles have a simple structure and a great variety,studies have shown that these compounds have important activities against plant pathogenic fungi.In order to develop new botanical agricultural fungicides,in this paper,indole-3-acetontrile was used as starting materical to synthesize core structure pyrroloindole,then synthesize some half-calycanthaceous alkaloids analogues and the biological activities of these compounds towards of bacteria and plant pathogen fungi were evaluated.The main research contents and results are as follows:1 First,indole-3-acetontrile was used as starting materical,using DMSO as the solvent and the oxidizing agent,with 37%HCl as a catalyst to form oxidation recation,then the compound IAN1 was obtained in 93%yield.2 Compound IAN1 were synthesized by using THF as the solvent,NaH as a ba$e,reacted with an excess of BnBr,C2H5I,C3H7I at the N-position and C-3 position,then give the products IAN2-1?IAN2-2 and IAN2-3,in 62%,58%,53%yield,respectively.3 Compound IAN2-1?IAN2-2 ? IAN2-3 were synthesized by using THF as the solvent,LiAIH4 as the reducing agent,form to cyclization reaction,then give the pyrroloindoles IAN3-1,IAN3-2 and IAN3-3 in 31%,45%,34%yield,respectively.4 The imine compounds IAN3 using anhydrous pyridine and triethylamine as the base,reacted with anhydride or acyl chloride,give 21 compounds that are the first kind of half-calycanthaceous alkaloids analogues IAN-1-1 to IAN-1-21.Moreover,compound IAN-1-1 to IAN-1-8 are aliphatic amides,and compound IAN-1-9 to IAN-1-18 are aromatic amides,which IAN-1-19 to IAN-1-21 are sulfonamides,then give 4 compounds that are the second kind of half-calycanthaceous alkaloids analogues IAN-4-1 to IAN-4-4,and then give 4 compounds that are the third kind of half-calycanthaceous alkaloids analogues IAN-5-1 to IAN-5-4,both of them are aliphatic amides..5 Indole-3-acetontrile was used as starting materica,compound IAN4 was gived by using THF as the solvent,NaH as a base,BnBr as the reaction reagent,the yield is 47%.6 The compound IAN5 was obtained in 73%yield by using DMSO as the solvent and the oxidizing agent,with 37%HCl as a catalyst to form oxidation reaction with compound IAN4.7 Compound IAN6-1 and IAN6-2 were gived in 74%and 82%yield,respectively by using THF as the solvent,NaH as a base,reacted with an excess of C2H5I or C3H5Br at the N-position and C-3 position of compound IAN5.8 Compound IAN7-1 and IAN7-2 were gived in 44%,47%yield,respectively by using THF as the solvent,LiAIH4 as the reducing agent,form to cyclization reaction with compound IAN6.9 Imine compounds IAN7 was used as substrate,anhydrous pyridine and triethylamine were used as the base,reacted with anhydride or acyl chloride,then give 2 half-calycanthaceous alkaloids analogues IAN-2-1 and IAN-3-1.10 All the synthesized 31 compounds have never been reported,and they were characterized by 1H-NMR,13C-NMR,DEPT(135 °).11 Disk diffusion antibiotic testing was utilized,with streptomycin sulfate as a positive control,to evaluate the biological activities of the first kind of half-calycanthaceous alkaloids analogues against Bacillus cereus,Staphylococcus aureus,Bacillus subtilis,Escherichia coli,Ralstonia solanacearum,and Pseudomonas aeruginosa.The results showed that,compound IAN-1-1,IAN-1-2 and IAN-1-3 exhibited a certain activity towards Pseudomonas aeruginosa and Bacillus subtilis.Compound IAN-1-1,IAN-1-2,IAN-1-3,IAN-1-12 and IAN-1-21 exhibited a certain activity towards Escherichia coli.Other compounds do not exhibited activity towards all of six bacteria.12 Mycelium growth inhibition assay was utilized,with carbendazim as a positive control,to evaluate the biological activities of 5 compounds which are the first kind of half-calycanthaceous alkaloids analogues against Eggplant Verticillium,Fusarium oxysporum,Colletotrichum gloesporioides,Alternaria alternate,Gibberella zeae,Botrytis cinerea,Curvularia lunata.The results showed that,both of the five compounds exhibited high degrees of activity against Colletotrochum gloesporioides and Gibbrella zeae,among the inhibition ratios of all the compound can reach over 50%.The inhibition ratios of compound IAN-1-12 reach 69.16%.Moreover,compound IAN-1-15 exhibited a certain activity towards Fusarium oxysporum and Curvularia lunata.