合成解除鹼基辨識序列限制之仿核酸

• Main Authors: Hui-Chen Lo, 羅惠珍
• Other Authors: Tsung-Mei Chin
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/42322339131033346544

碩士 === 中國文化大學 === 應用化學研究所 === 88 === Oligonucleotide-directed triple helix formation is one of the most versatile methods for the sequence-specific recognition of duplex DNA. The binding specificity is derived from the formation of hydrogen bonds between bases in the third strand and duplex base pairs. However, the binding of the third strand specifies mostly to purine tracts of duplex nucleic acid. This limits the application of a triplex. A nucleoside analog 2'-deoxy-5-azacytidine has a pyrimidine-like base, 5-azacytosine (aC). The structure of 5-azacytosine differs from the natural base cytosine in substitution of a carbon atom by a nitrogen atom, which is able to provide an extra hydrogen bond to form T•aCG and GaC•A base triads. Thus, 5-azacytosine, capable of binding mixed purine/pyrimidine sequences, may be able to expand the recognition code of a triplex. In this thesis, we developed a synthetic method for 2'-deoxy-5-azacytidine through glycosylation of the α-chlorosugar with the base. Theα-chlorosugar was derived from cyclization and chlorination of 2'-deoxy-D-ribose carried out in a 1,4-dioxane solution of hydrogen chloride. This improved procedure allowed the synthesis of the 1-chloro-2-deoxy-α-D-ribofuranoside derivative and offered ease of handling, high yield and the stereo-controlled α-configuration at C-1. The direct condensation ofα-chlorosugar with the silylated 5-azacytosine base under proper conditions via SnCl4 provided the β-3',5'-ditoluoyl-2'-deoxy-5-azacytidine which was crystallized from ethyl acetate. It was also found that to obtained a good yield of 2'-deoxy-5-azacytidine, the remove of 3'- and 5'-protecting groups had to be performed in the neutral conditions by cyanide ion in methanol.