Nucleotide analogues, and preparation and application thereof

A method for synthesizing a nucleotide analogue, comprising:

• (1) dissolving a compound A1 in dichloromethane followed by addition of Dess-Martin periodinane and NaHCO3 and reaction at room temperature for 5-16 h to obtain a compound A2;
• (2) dissolving ethyl (triphenylphosphoranylidene) acetate in dichloromethane followed by addition of a dichloromethane solution of the compound A2 under stirring and reaction at room temperature for 5-16 h to obtain a compound A3;
• (3) dissolving the compound A3 in dichloromethane followed by addition of diisobutyl aluminum hydride and reaction at −10° C.-5° C. for 1-3 h to obtain a compound A4;
• (4) dissolving tetraisopropyl titanate in dichloromethane followed by addition of diethyl D-(−)-tartrate under stirring at −30° C.-5° C., addition of a dichloromethane solution of the compound A4 and tert-butyl hydroperoxide, and reaction for 10-24 h to obtain a compound A5;
• (5) dissolving the compound A5 in pyridine followed by addition of a hydroxyl protecting group reagent and reaction at room temperature under stirring for 5-16 h to obtain a compound A6;
• (6) dissolving the compound A6, a nucleotide base reagent and 1,8-diazabicyclo [5.4.0] undec-7-ene in a solvent in a microwave reaction tube followed by reaction under stirring at 90-120° C. for 5-12 h to obtain a compound A7;
• and
• (7) dissolving the compound A7 in dichloromethane followed by addition of 4,5-dicyanoimidazole and 2-cyanoethyl N,N,N′,N′-tetraisopropyl-phosphordiamidite and reaction at 20-40° C. for 20 min-3 h to obtain a compound A8;
• as shown in the following synthesis route:

A small interfering RNA (siRNA), comprising:

• a sense strand;
• and
• an antisense strand;
• wherein the sense strand and the antisense strand each comprise 15-45 nucleotides which are each independently modified or unmodified;
• the sense strand and the antisense strand are partially complementary to form a double-stranded region;
• and
• the sense strand comprises at least one nucleotide represented by Formula (V) in the 15-45 nucleotides:
• the at least one nucleotide represented by Formula (V) is covalently linked to other parts of the siRNA at position;
• wherein X is O or S;
• L is a lipophilic group;
• and
• Base is a nucleotide base.