| Summary: | 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 double helical DNA. The specificity is derived from the formation of hydrogen bonds between bases in the third strand and duplex base pairs. So far, there are two classes of base triads, including Py‧PuPy and Pu‧PuPy. Design leads to expand the recognition code to pyrimidine-purine base pairs (Py‧PyPu or Pu‧PyPu). According to molecular modeling, 5-azacytosine, a pyrimidine-like base, is able to simultaneously provide the Watson-Crick and Hoogsteen hydrogen bonds. Thus, the nucleoside analog 2''-O-allyl-5-azacytidine may be able to eliminate the limitation of base sequence recognition, and enhance the binding affinity and nuclease resistance.
In this thesis, we developed a synthetic method for 2''-O-allyl-5-azacytidine. The 3''- and 5''-hydroxy groups of the starting material 5-azacytidine was first regioselectively silylated by 1,3-dichloro-1,1,3,3,-tetraisopropyldisiloxane to give 3'',5''-diprotected nucleoside, in which only the 2''-hydroxy group was available for modification. Then, the 2''-hydroxy group was converted to 2''-O-allyl group under the catalytic reaction of organometallic reagent Pd(0). In these two steps, the reactions were very sensitive to the moisture. It was found that the anhydrous reaction conditions as well as the properly controlled reaction time and temperature were required to obtain good yields. After removing the silyl group by treatment of n-Bu4NF, 2''-O-allyl-5-azacytidine was obtained in a white solid by crystallization from methanol.
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