在核苷酸位置-2'置放取代基的合成研究

• Main Author: 郭浚彥
• Other Authors: 靳宗玫
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/82991594668892588453

碩士 === 中國文化大學 === 應用化學研究所 === 91 === The artificial oligonucleotides are important in the fields of the gene therapy and the gene detector in medical science and academia. The oligonucleotide has two main puckered shapes that are C2''-endo and C3''-endo. The nucleic acid duplex with C3''-endo conformation is stabler than that of C2''-endo conformation. The advantages of designated modifications at the 2''-hydroxyl group include stabilization of RNA oligonucleotides during synthesis, increased nuclease resistance and enhancement of duplex stability upon hybridization to target sequences. Thus, it is necessary to improve the synthetic method of the uridine derivation with OCH2CH=CH2 substitution on the 2''-position. The natural uridine has moderate selectivity in alkylation of the 2''-hydroxyl group, 3''-hydroxyl group, 5''-hydroxyl group and N3-location. Thus, the 3''-hydroxyl group and 5''-hydroxyl group were protected by a TIPDS group, and the N3-location by a toluoyl group. The allyl substitution on the 2''-hydroxy group was performed by treatment of ally with Pd(0) and dppd under argon. After deprotection of 3'', 5''-TIPDS group and N3 toluoyl group, the 2''-O-allyluridine was obtained. In order to application on a DNA synthesizer, further activated the 2''-O-allyluridine by dimethoxytrityluridine group on the position of 5''-hydroxy group.