2',3'-di-O-levulinoyl-2-N-(9-fluorenylmethoxycarbonyl)guanosine | 135944-30-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-di-O-levulinoyl-2-N-(9-fluorenylmethoxycarbonyl)guanosine
• 英文别名: [(2R,3R,4R,5R)-5-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-oxo-3H-purin-9-yl]-2-(hydroxymethyl)-4-(4-oxopentanoyloxy)oxolan-3-yl] 4-oxopentanoate
• CAS: 135944-30-8
• 化学式: C₃₅H₃₅N₅O₁₁
• 分子量: 701.69
• InChiKey: YMYLAUWDSYWHBP-QCVVPRSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  51.0
• 可旋转键数：
  13.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  218.1
• 氢给体数：
  3.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  2',3'-di-O-levulinoyl-2-N-(9-fluorenylmethoxycarbonyl)guanosine 、 (9-{(2R,3R,4R,5R)-4-(Diisopropylamino-methoxy-phosphanyloxy)-3-methoxy-5-[(4-methoxy-phenyl)-diphenyl-methoxymethyl]-tetrahydro-furan-2-yl}-9H-purin-6-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester 在 四氮唑 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  Synthesis and conformational analysis of phosphate-methylated RNA dinucleotides

  摘要：

  Synthesis of RNA dimers having a methyl phosphotriester group as the internucleoside linkage is reported; six pairs of diasteroisomerically pure systems were prepared, i.e, r(CpU) (15), r(ApU) (16), r(CpC) (17), r(ApC) (18), r(CpG) (19), and r(ApG) (20). Compounds 15-20 are stabilized by a 2'-O-methyl group in the 5'-terminal residue. The present systems represent the third class of backbone-modified RNA oligomers, following the 2'-O-methylribonucleotide phosphorothioates and the 2'-O-methylribonucleotide methyl phosphonates. Our synthetic approach comprises the use of 9-fluorenylmethoxycarbonyl (Fmoc) groups for transient protection of the exocyclic NH2 groups of the bases A, C, and G, levulinoyl (Lev) groups for the transient protection of the 2'-and 3'-OH groups of the 3'-terminal residues, methanolic K2CO3 for the simultaneous removal of Fmoc and Lev groups with full preservation of the methyl phosphotriester function, and finally reversed-phase HPLC separation of the S(P) and R(P) diastereoisomers. The availability of the six dimers in diastereoisomerically pure form enabled us to examine the molecular conformations using high-field NMR and circular dichroism (CD) spectroscopy. These studies led to the following conclusions: (i) NMR J-coupling analysis: the central C4'-C5' (gamma) and C5'-O5' (beta) bonds in 15-20 show less preference for the gamma+ and beta-t rotamers, in comparison with their natural analogues, i.e., base stacking is diminished upon introduction of the two methyl groups on O2' and on the phosphate methyl groups on O2' and on the phosphate group; (ii) CD analysis: 15-20 show substantially reduced molecular ellipticities when compared to the natural counterparts, which also reveals that base stacking is reduced; (iii) UV and variable-temperature H-1 NMR measurements: (S(P)- and (R(P))-19 show self-association, via the formation of a right-handed miniduplex with two C-G base pairs ((S(P)-19, T(m) = 9.3-degrees-C, concn = 36.6-mu-M; (R(P))-19, T(m) = 8.7-degrees-C, concn = 48.1-mu-M). The present conformational data on (R(P))- and (S(P))-15-20 are in agreement with literature data on other phosphate-triesterified oligonucleotides, e.g., the trimer d(T(POEt)G(POEt)G) and the tetramer d(T(POEt)T(POEt)C(POEt)A). While the latter systems also showed little base-base stacking, it was established that they readily form a local duplex with a complementary natural RNA sequence. Hence we anticipate that phosphate-methylated 2'-O-methyl-RNA oligomers, longer than the dimer systems described in the present work, will also hybridize easily with complementary natural RNA.

  DOI：

  10.1021/jo00020a028
• 作为产物：
  描述：

  鸟苷 在 吡啶 、 溶剂黄146 作用下， 反应 55.0h， 生成 2',3'-di-O-levulinoyl-2-N-(9-fluorenylmethoxycarbonyl)guanosine
  参考文献：
  名称：

  Synthesis and conformational analysis of phosphate-methylated RNA dinucleotides

  摘要：

  Synthesis of RNA dimers having a methyl phosphotriester group as the internucleoside linkage is reported; six pairs of diasteroisomerically pure systems were prepared, i.e, r(CpU) (15), r(ApU) (16), r(CpC) (17), r(ApC) (18), r(CpG) (19), and r(ApG) (20). Compounds 15-20 are stabilized by a 2'-O-methyl group in the 5'-terminal residue. The present systems represent the third class of backbone-modified RNA oligomers, following the 2'-O-methylribonucleotide phosphorothioates and the 2'-O-methylribonucleotide methyl phosphonates. Our synthetic approach comprises the use of 9-fluorenylmethoxycarbonyl (Fmoc) groups for transient protection of the exocyclic NH2 groups of the bases A, C, and G, levulinoyl (Lev) groups for the transient protection of the 2'-and 3'-OH groups of the 3'-terminal residues, methanolic K2CO3 for the simultaneous removal of Fmoc and Lev groups with full preservation of the methyl phosphotriester function, and finally reversed-phase HPLC separation of the S(P) and R(P) diastereoisomers. The availability of the six dimers in diastereoisomerically pure form enabled us to examine the molecular conformations using high-field NMR and circular dichroism (CD) spectroscopy. These studies led to the following conclusions: (i) NMR J-coupling analysis: the central C4'-C5' (gamma) and C5'-O5' (beta) bonds in 15-20 show less preference for the gamma+ and beta-t rotamers, in comparison with their natural analogues, i.e., base stacking is diminished upon introduction of the two methyl groups on O2' and on the phosphate methyl groups on O2' and on the phosphate group; (ii) CD analysis: 15-20 show substantially reduced molecular ellipticities when compared to the natural counterparts, which also reveals that base stacking is reduced; (iii) UV and variable-temperature H-1 NMR measurements: (S(P)- and (R(P))-19 show self-association, via the formation of a right-handed miniduplex with two C-G base pairs ((S(P)-19, T(m) = 9.3-degrees-C, concn = 36.6-mu-M; (R(P))-19, T(m) = 8.7-degrees-C, concn = 48.1-mu-M). The present conformational data on (R(P))- and (S(P))-15-20 are in agreement with literature data on other phosphate-triesterified oligonucleotides, e.g., the trimer d(T(POEt)G(POEt)G) and the tetramer d(T(POEt)T(POEt)C(POEt)A). While the latter systems also showed little base-base stacking, it was established that they readily form a local duplex with a complementary natural RNA sequence. Hence we anticipate that phosphate-methylated 2'-O-methyl-RNA oligomers, longer than the dimer systems described in the present work, will also hybridize easily with complementary natural RNA.

  DOI：

  10.1021/jo00020a028