2-[(2R,3R,5S)-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-nitrooxolan-3-yl]acetaldehyde | 1026259-68-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2-[(2R,3R,5S)-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-nitrooxolan-3-yl]acetaldehyde
• CAS: 1026259-68-6
• 化学式: C₁₂H₁₅N₃O₇
• 分子量: 313.267
• InChiKey: DZSFAVWXXHSHCP-KGIIMIRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[(2R,3R,5S)-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-nitrooxolan-3-yl]acetaldehyde 在 吡啶 、 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 2-[(2R,3R,4R,5S)-5-(acetyloxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-nitrooxolan-3-yl]ethyl acetate
  参考文献：
  名称：

  [4 + 2] and [3 + 2] Cycloaddition reactions of 2',3'-dideoxy-3'-nitro-2',3'-didehydrothymidine with ethyl vinyl ether

  摘要：

  Cycloaddition reaction of 1-(5'-O-(monomethoxytrityl)-2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1a) with ethyl vinyl ether gave a diastereomeric mixture of [3.4.0]sugar-fused bicyclic (2a) (27%) and (3) (12%) and the tricyclic (4a) (47%) derivatives. An identical reaction with (2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1b) gave only bicyclic 2b (40%) and tricyclic 4b (43%) in a stereospecific manner. Chemical evidence has been presented which suggests that only one of the diastereomeric nitronates (i.e., 2a) formed as a result of [4 + 2] addition reaction across a 4pi heterodiene system undergoes the second [3 + 2] cycloaddition reaction across its nitronate function by a second molecule of the reagent to give the tricyclic product 4a. The configurations of new chiral centers have been assigned as C2'-R/C8-R in 2a and 2b, C2'-R/C8-S in 3, and C2'-R/C3'-S/C8-R/C12-S in 4a and 4b by detailed 500-MHz NMR studies. Detailed analysis Of 3J(HH) coupling constants at 500 MHz and estimation of interproton distances by 1D H-1 difference NOE and the NOESY spectra have enabled us to define the conformation of novel thymidine derivatives 2b, 3, and 4b: (i) The pentose sugars in 2b and 3 are 2'-endo-3'-exo (P = 142-degrees, PSI(m) = 34-degrees for 2b and P = 140-degrees, PSI(m) = 33-degrees for 3), and the constituent six-membered ring are in the half-chair/half-boat conformation. (ii) For tricyclic nucleoside 4b, the pentose sugar moiety adopts 2'-endo conformation (P = 161-degrees, PSI(m) = 40-degrees) with the fused six-membered ring in 09C(C2'), conformation, whereas the conformation of its fused-spiro isoxazolidine ring can be described by P = 188-degrees, PSI(m) = 40-degrees.

  DOI：

  10.1021/jo00062a036
• 作为产物：
  描述：

  5'-O-(4-Monomethoxytrityl)-3'-nitro-2',3'-dideoxy-2',3'-didehydrothymidine 在 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 生成 2-[(2R,3R,5S)-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-nitrooxolan-3-yl]acetaldehyde
  参考文献：
  名称：

  [4 + 2] and [3 + 2] Cycloaddition reactions of 2',3'-dideoxy-3'-nitro-2',3'-didehydrothymidine with ethyl vinyl ether

  摘要：

  Cycloaddition reaction of 1-(5'-O-(monomethoxytrityl)-2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1a) with ethyl vinyl ether gave a diastereomeric mixture of [3.4.0]sugar-fused bicyclic (2a) (27%) and (3) (12%) and the tricyclic (4a) (47%) derivatives. An identical reaction with (2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1b) gave only bicyclic 2b (40%) and tricyclic 4b (43%) in a stereospecific manner. Chemical evidence has been presented which suggests that only one of the diastereomeric nitronates (i.e., 2a) formed as a result of [4 + 2] addition reaction across a 4pi heterodiene system undergoes the second [3 + 2] cycloaddition reaction across its nitronate function by a second molecule of the reagent to give the tricyclic product 4a. The configurations of new chiral centers have been assigned as C2'-R/C8-R in 2a and 2b, C2'-R/C8-S in 3, and C2'-R/C3'-S/C8-R/C12-S in 4a and 4b by detailed 500-MHz NMR studies. Detailed analysis Of 3J(HH) coupling constants at 500 MHz and estimation of interproton distances by 1D H-1 difference NOE and the NOESY spectra have enabled us to define the conformation of novel thymidine derivatives 2b, 3, and 4b: (i) The pentose sugars in 2b and 3 are 2'-endo-3'-exo (P = 142-degrees, PSI(m) = 34-degrees for 2b and P = 140-degrees, PSI(m) = 33-degrees for 3), and the constituent six-membered ring are in the half-chair/half-boat conformation. (ii) For tricyclic nucleoside 4b, the pentose sugar moiety adopts 2'-endo conformation (P = 161-degrees, PSI(m) = 40-degrees) with the fused six-membered ring in 09C(C2'), conformation, whereas the conformation of its fused-spiro isoxazolidine ring can be described by P = 188-degrees, PSI(m) = 40-degrees.

  DOI：

  10.1021/jo00062a036

文献信息

• [4 + 2] and [3 + 2] Cycloaddition reactions of 2',3'-dideoxy-3'-nitro-2',3'-didehydrothymidine with ethyl vinyl ether
  作者：Alexander Papchikhin、Peter Agback、Janez Plavec、Jyoti Chattopadhyaya

  DOI：10.1021/jo00062a036

  日期：1993.5

  Cycloaddition reaction of 1-(5'-O-(monomethoxytrityl)-2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1a) with ethyl vinyl ether gave a diastereomeric mixture of [3.4.0]sugar-fused bicyclic (2a) (27%) and (3) (12%) and the tricyclic (4a) (47%) derivatives. An identical reaction with (2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1b) gave only bicyclic 2b (40%) and tricyclic 4b (43%) in a stereospecific manner. Chemical evidence has been presented which suggests that only one of the diastereomeric nitronates (i.e., 2a) formed as a result of [4 + 2] addition reaction across a 4pi heterodiene system undergoes the second [3 + 2] cycloaddition reaction across its nitronate function by a second molecule of the reagent to give the tricyclic product 4a. The configurations of new chiral centers have been assigned as C2'-R/C8-R in 2a and 2b, C2'-R/C8-S in 3, and C2'-R/C3'-S/C8-R/C12-S in 4a and 4b by detailed 500-MHz NMR studies. Detailed analysis Of 3J(HH) coupling constants at 500 MHz and estimation of interproton distances by 1D H-1 difference NOE and the NOESY spectra have enabled us to define the conformation of novel thymidine derivatives 2b, 3, and 4b: (i) The pentose sugars in 2b and 3 are 2'-endo-3'-exo (P = 142-degrees, PSI(m) = 34-degrees for 2b and P = 140-degrees, PSI(m) = 33-degrees for 3), and the constituent six-membered ring are in the half-chair/half-boat conformation. (ii) For tricyclic nucleoside 4b, the pentose sugar moiety adopts 2'-endo conformation (P = 161-degrees, PSI(m) = 40-degrees) with the fused six-membered ring in 09C(C2'), conformation, whereas the conformation of its fused-spiro isoxazolidine ring can be described by P = 188-degrees, PSI(m) = 40-degrees.