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Development of New Antiviral Compounds and Novel DNA Cleaving Agents
Dissertation

Development of New Antiviral Compounds and Novel DNA Cleaving Agents

Shih Hsien Chuang
Doctor of Philosophy (PHD), 國立清華大學, 化學系
2004

Abstract

丹酚酸丙 去氧核醣核酸切割試劑 丹參 氧化偶氮化合物 鳥糞嘌呤 單股螺旋的切割 single-strand DNA cleavage benzo[c]cinnoline N-oxide Salvia miltiorrhiza salvianolic acid C rosmarinic acid, lithospermic acid
In this thesis, I develop a synthetic route for the preparation of salvianolic acid C, rosmarinic acid, and lithospermic acid derivatives. I also explore the RNA cleaving ability and antiviral activities of benzo[c]cinnoline N-oxide, which can cleave DNA upon UV irradiation. Furthermore, I report a photo-induced DNA cleaving processes by using ruthenium and osmium oximates under aerobic conditions. In Part 1 of this thesis, derivatives of phenolic acids extracted from Salvia miltiorrhiza were synthesized. These phenolic acids including heptamethyl lithospermic acid derivative, hexamethyl salvianolic acid C, and pentamethyl rosmarinic acid. The key step involved a Heck-type coupling followed by cyclization. In Part 2, I found one of the azoxy compound, benzo[c]cinnoline N-oxide, can cleave RNA upon exposure to UV light. Under irradiation with UV light at 365 nm for 30 minutes, benzo[c]cinnoline N-oxide was able to inactivate herpes simplex virus type I in three strains. Through polymerase chain reaction, the DNA of azoxy treated virus were cleaved. Moreover, I demonstrated that benzo[c]cinnoline N-oxide cleaved DNA dominantly at the guanine residue by photolysis with UV light at 365 nm. In Part 3, I reported that single-strand DNA cleavage can be accomplished by photolysis of di- and triruthenium complexes and triosmium oximates with exposure to 350-nm UV light under aerobic conditions. This photo-induced cleaving process was pH-dependent over pH 5.0–8.0 and exhibited the greatest cleaving ability at acidic condition at pH 5.0.

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