Synthesis And In Vitro Antimicrobial Activity Study Of Pogostone And Its Analogues

The pogostone is one of the main effective components of Pogostemon cablin (Blanco) Benth. In vitro experiments indicated that it significantly inhibited Candida albicans, Cryptococcus neoformans, black Rhizopus fungi, and has a certain inhibition to staphylococcus ayreus and alpha hemolytic streptococcus. The literature search discovered that the2-pyrone ring may be the effective groups of pogostone in antimicrobial activity. So we started a job to synthesize the pogostone analogs and carried out the screening studies of antimicrobial activity including several pathogens such as candida albicans.Objects1To improve and optimize the chemical synthesis process of pogostone.2To synthesize the pogostone analogs and win the target. Carry on the structure appraisal to them.3Carry out the screening studies of antibiotic activity including several pathogens such as candida albicans, in order to get a better antibacterial activity of compounds.Method1Take pogostone as the lead compound, transform and modify the third substituent group on2-pyrone ring. Based on the above ideas, we designed the.following two processes of synthesis.Synthetic route one:Take4-hydroxy-6-methyl-2-pyrone as reactants, to react with Organic alkyl acid in the toluene solution that added DMAP and DCC. The Reaction is C-acylation reaction.Synthetic route two: Use of reference method, take DHA as reactants to react with organic aldehyde in the THF solution that added diethylamine, prepared from the intermediate, then catalytic hydrogenation win the target compounds.2The products were subjected to alkali-soluble and acid precipitation, silica gel column chromatography and recrystallization. The High Performance Liquid Chromatography (HPLC) was used to monitor the synthesis and separation processes. The obtained compounds with purity≥95%were identified on the. four spectrum technologies.3Anti-white candida activity study in vitro of the target compounds with medium dilution method; Against Escherichia coli and other pathogenic bacteria activity study of the target compounds with trace of liquid-based dilution method.ResultsTotal of14compounds were prepared by two synthetic routes, which routes one get10compounds and routes two get7compounds. Structural analysis proved that four compounds is the joint product of two routes, and they are all pogostone homologues. Two compounds are the pogostone analogues and two compounds are the byproduct isolated from synthetic pogostone by routes two.Antifungal experimental study to the synthesized products found that the pogostone homologues with a certain degree of anti-candida albicans activity,3-propanoyl-4-hydroxy-6-methyl-2-pyrone (compounds3),3-butyryl-4-hydroxy-6-methyl-2-pyrone (compounds4), and4-hydroxy-6-methyl-3-(3'-methylbutanoyl)-2-pyrone (compounds7) have the equal antifungal activity with pogostone.3-acetyl-4-hydroxy-6-methyl-2-pyrone (compounds) and3-heptanoyl-4-hydroxy-6-methyl-2-pyrone (compounds9) have weaker activity than pogostone.4-hydroxy-6-methyl-pentanoyl-2-pyrone (compounds6) and3-hexanoyl-4-hydroxy-6-methyl-2-pyrone (compounds8) have better activity than pogostone. Pogostone and its analogues had shown some antibacterial activity to Escherichia coli and other pathogenic, but the effect is not obvious.Antibacterial experimental study to the synthesized products found that the pogostone and its analogues had shown some antibacterial activity to Gram-positive bacteria such as Escherichia coli and Gram-negative bacteria such as Pneumococcus, but the effect is not obvious.ConclusionSynthetic route one has the following advantages, such as simple steps, low cost,targets easy to get and high conversion rate. If the process was further optimized, it can be used as the industrial production of pogostone. Confirm the antifungal activity of pogostone and its homologues great related with the2-pyrone ring, the structure of third substituent group and the carbon chain length can affect the biological activity of the compounds. We have found some compounds has good antibacterial activity by anti-candida albicans activity screening, and in the future more extensive pharmacodynamic screening will be done to these compounds, with a view to new discoveries.