Molecular Design of Hypervalent Iodine and Development of Drugs

以有机硅烷为原料，通过硅-碘交换反应制备了多种烯基和炔基（苯基）碘烷。并与两性霉素B和酮康唑的体外和体内抑菌活性进行了比较。(E)-1-十二烷基甘烷的体外抑菌活性较弱。n -辛基烷在低药物浓度下表现出广泛的体外抗真菌活性，抑制白色念珠菌的生长。这些烯基和炔基内酯在体内没有抗真菌活性。研究了炔基（苯基）碘烷的DNA切割活性，通过监测闭合环状（形式I）到开环状（形式II）和线性（形式III） DNA的转化。乙基（苯基）碘烷和丙基（苯基）碘烷具有中等的裂解效率。作为一类有效的抗肿瘤抗生素neocarzinostatin的化学模型，在酸性介质中，萘酸酯基的邻基参与产生的γ-氧烯酮缩醛中间体产生的烯二炔衍生物的Myers-Saito型环化反应。还研究了烯二炔模型化合物的脱羧环芳构化反应。

A variety of alkenyl- and alkynyl(phenyl)iodanes were prepared from organosilanes via silicon-iodane exchange reations. The in vitro and in vivo antifungal activity of these organoidanes were studied and compared with that of amphotericin B and ketoconazole. (E)-1-Decenyliodane showed the weak in vitro antifungal activity. N-Octynyliodane showed a broad in vitro antifungal activity at low drug concentrations, inhibiting growth of Candida albicans. These alkenyl- and alkynyliodanes showed no in vivo antifungal activity.DNA-cleaving activity of alkynyl(phenyl)iodanes was investigated by monitoring the conversion of closed circular (form I) to open circular (form II) and linear (form III) DNA. Ethynyl(phenyl)iodane and propynyl(phenyl)iodane showed moderate cleavage efficiency.As a chemical model for a class of potent antitumor antibiotics, neocarzinostatin, the Myers-Saito type cyclizations of enediyne derivatives via γ- oxo ketene acetal intermediates generated by the neighboring group participation of naphtoate ester groups in acidic media were developed. Decarboxylative cycloaromatization of enediyne model compounds was also investigated.