5-甲基胞嘧啶锁核酸的合成新方法

A New Synthetic Method of 5-Methylcytosine Locked Nucleic Acid

设计了一种新的合成5-甲基胞嘧啶锁核酸{(1R,3R,4R,7S)-3-[(5-甲基-4-N-苯甲酰基胞嘧啶-1-基)-7-(2-氰基乙氧基)-(N,N-二异丙基)膦氧代]-1-(4,4'-二甲氧基三苯代甲基氧基甲基)-2,5-二氧杂二环-[2.2.1]庚烷(1)}的方法。以3-苄氧基-4-C-羟甲基-1,2-O-异亚丙基-α-D-呋喃核糖为起始原料,经取代、水解等12步反应合成了1,总收率21.0%,其结构经1H NMR和MS确证。

A new synthetic route of 5-methylcytosine LNA t （ 1 R, 3R, 4R, 7S） -7- [ 2-cyanoethoxy （ dii- sopropylamino ） phosphinoxy ] -1- （ 4,4 ＇-dimethoxytrityloxymethyi ） -3 - （ 5-methyl4-N-benzoylcytosine-l- yl）-2,5-dioxabicyclo[2.2.1 ] heptan （1） I was developed. 1 with the total yield of 21.0% was syn- thesized by a twelve-step reaction of substitution reaction and hydrolysis reaction, etc, using furanose 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-ot-D-ribofuranose as the starting material. The structure was confirmed by 1H NMR and MS.