Studies On The Synthesis, Characterization And Biological Activities Of P450-14DM Inhibitors

Triazole compounds have been found to show wide spread biological activities, many of them have been developed and used as fungicides, plant growth regulators and medicine. Some of them have more than 100 million dollars sale a year, propiconazole is one of them , used as agricultural fungicide, its total sale per year surpasses 200 million dollars. Another one is fluconazole, used as medicine, the total sale reaches 1500 million dollars per year. Triazole compounds have been the most important of types of fungicides in nitrogen heterocyclic compounds. Different structures of triazole compounds have different biological activities, developing novel structural triazole compounds is the research focus at present.In this thesis, We have reviewed the recent advances in the studies on the structures, synthesis, action mechanism, structure-activity relationship and biological activities of triazo'les, different active groups of action mechanism were inducted into the triazole compounds according to the concept of bioisosterism. One hundred and six novel triazole compounds in fifteen types of structure were designed and synthesized and their structures were confirmed by means of 1HNMR, IR, MS, EA and crystal structure determination. Spectral properties and biological activities were also researched and some of them were found to show good fungicidal activities and plant growth regulation activities. The contents and the primary contributions of the research are summarized as follows:1) Pyrimidine ring, 1,3-dithiolan ring, thiophene ring, 1,3-thiazolidine ring and thiadi -zole ring were inducted into structures of triazoles for the first time. Theirsynthesis methods, crystal structures and spectral properties were researched, respectively. The results of bioactivity test show that their fungicidal activities are not good except of triazoles bearing thiadizole ring.2) New manner of cyclization of thiophene ring was found by crystal structure determination, novel triazole compounds of triazole ring attached thiophene ring were synthesized for the first time. Bioactivity test shows that so many heterocycles or phenyl rings arrounding the triazole ring is not good for the biological activities.3) Novel tiazole compounds containing pentanethiomide group were synthesized for the first time. The crystal structure determination shows that triazole ring and phenyl ring is not planar, but the exposed sulphur atom might compete with nitrogen atom of triazole ring in inhibiting center iron atom of P-450, leading to the fungicidal activities are not high.4) New method for preparing intermediates 2-(l,2,4-triazole-l-yl)-aryl (or alkyl) ethanone was achieved, the yield and purity are both higher.5) Novel triazole compounds containing N, A/-dialkyldithiocarbamate were desi -gned and synthesized for the first time, the crystal structure of one of them was determined, the results of their biological tests show that the synthesized compounds have better comprehensive inhibiting efficiency towards tested fungus than triadimefon. Some of them possess the potency of commercialization.6) Novel triazole compounds containing arylsulphur group were designed and synthesized according to the concept of bioisosterism. Their bioactivities are mainly effected by R group. When R is t-Bu, corresponding compounds synthesized have the inhibiting rate of 100% towards wheat rust fungus at 50ug/mL.7) Novel triazole compounds containing 1,3-dioxiolane were synthesized by utilizing 3-chloro-l, 2-propanediol instead of butanedial or pentanediol. This type of the structure belongs to the one's of high activities. When R is 2,4-Cl2C6H3, thecomprehensive inhibiting rate towards tested fungus reaches A grade ( > 90%).8) Novel triazole compounds as the analogues of difenoconazole were designed and synthesized for the first time. The result of bioactivity test shows that the existence of the methylene on the phenyl group destroys the conjugation system of the molecular, leading to the lower fungicidal activities.9) Novel...