| Part Ⅰ Synthesis of Streptococcus Mutans Sortase A inhibitorsStreptococcus mutans is one of the normal oral bacteria colonization, as long as the keypathogen of dental caries. Sortase A enzyme is the key enzyme of dental caries, andStreptococcus mutans cariogenic capacity will diminish when sortase A enzyme is inhibited.Finding out an inhibitor under the condition of sortase A enzyme IC50value less than theMIC value against bacteria can be used as a new anticaries way. Both Staphylococcus aureusand Streptococcus mutans are gram-positive bacteria, and their amino acid sequencesimilarity is27%and they have the same active sites. So the research of staphylococcusaureus sortase A inhibitors is an important reference for streptococcus mutans sortase Ainhibitors study. According to Staphylococcus aureus sortase A inhibitors reported, screeningout Streptococcus mutans sortase A inhibitors and the research finds outbromodeoxytopsentin, morin and phenyl vinyl sulfone having inhibitory activity. This articleis about the synthesis research of morin and phenyl vinyl sulfone derivatives, in order toprovide the screening substrates and achieve better caries prevention.This paper firstly selects isoflavone and phenyl vinyl sulfone compounds to research.Phloroglucinol with various substituted phenylacetonitrile via the Hoesch reaction,hydrolysis reaction, the cyclization reaction to prepare5,7-dihydroxy-3-phenyl-isoflavone,4’,5,7-trihydroxy isoflavone,5,7-dihydroxy-4’-methoxyisoflavone,5,7-dihydroxy-3-(4-nitrophenyl)-isoflavone; Resorcinol with4-hydroxyphenylacetic acid,using the "one-pot" method to prepare4’,7-dihydroxyisoflavone; Thiophenol with1,2-dichloroethane, after the substitution reaction, oxidation reaction, elimination reaction, toprepare phenyl vinyl sulfone; cinnamic acid via decarboxylation halogenation reaction, andthen the intermediate via the coupling reaction with thiophenol, the oxidation reaction, toprepare β-phenylsulfonylstyrene. Different cinnamic acid substituents as raw material canprepare a series of phenyl vinyl sulfone derivatives.7compounds had been prepared successfully in this article. Final products and intermediates were verified via NMR identification, and the products had been confirmed.The synthetic routes which adopted in this article had provided a methodological basis forpreparation of two series derivatives. The prepared compounds had provided the materialbasis for screening more optimized inhibitors. Further work will detect the sortase A enzymeinhibition ability of derivatives as well as the toxicity of Streptococcus mutans, in order todesign more optimized inhibitors. We will also observe the biofilm impact and conductanimal experiments about Streptococcus mutans, in order to select better inhibitors for dentalcaries prevention.Part Ⅱ Synthesis of Ethinylestradiol Degradation ProductsWhen ethinylestradiol raw material stored for a long time, some degradation productswere found by HPLC analysis, and the structure of these degradation products were alsoconfirmed by LC-MS. The synthesis of4kinds of degradation products of ethinyl estradiol,Δ9,11-Ethinylestradiol,6-hydroxy-ethinylestradiol,6β-hydroxy-ethinylestradiol and6-keto-ethinylestradiol, will be studied in this section. At the same time, a long-actingsteroid compounds quinestrol were also prepared in this section. Norethindrone via theaccelerated oxidation reaction to prepae6-keto-ethinylestradiol;6-keto-ethinylestradiolas reactant via reduction reaction with sodium borohydride to prepare a pair of opticalisomers of6-hydroxyl-ethinylestradiol and6β-hydroxyl ethinylestradiol;ethinylestradiol via oxidation reaction with2,3-dichloro-5,6-dicyano-1,4-benzoquinone to obtain Δ9,11-ethinylestradiol; ethinylestradiol and bromocyclopentane viawiliamson reaction to prepare quinestrol. We had successfully prepared the four kinds ofdegradation products of ethinyl estradiol and quinestrol, and the structure of thesecompounds were verified via the NMR identification, and the products had been confirmed. |
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