1-<(Benzyloxy)methyl>-7-<2'-deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione | 159626-11-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-<(Benzyloxy)methyl>-7-<2'-deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione
• 英文别名: β-2'-deoxyribosyl-5-methoxycarbonyl-pyrrolo<2,3-d>pyrimidin-2,4-dione；methyl 3-(methoxymethyl)-7-[(2R,4S,5R)-4-(4-methylbenzoyl)oxy-5-[(4-methylbenzoyl)oxymethyl]oxolan-2-yl]-2,4-dioxo-1-(phenylmethoxymethyl)pyrrolo[2,3-d]pyrimidine-5-carboxylate
• CAS: 159626-11-6
• 化学式: C₃₉H₃₉N₃O₁₁
• 分子量: 725.752
• InChiKey: XPAGMPZRJKSBQI-DCMFLLSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  53
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  152
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1-<(Benzyloxy)methyl>-7-<2'-deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione 在 palladium dihydroxide 氢气 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 57.83h， 生成 2-(Benzoylamino)-7-<2'-deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-5-(methoxycarbonyl)pyrrolo<2,3-d>pyrimidin-4(3H)-one
  参考文献：
  名称：

  A New Synthetic Route to .beta.-2'-Deoxyribosyl-5-Substituted Pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-Deoxycadeguomycin

  摘要：

  A new and flexible synthetic route to beta-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines has been developed. Formation of the pyrrole ring is effected by combining sodium N-(4-nitrophenethyl)-glycinate with a differently protected 6-chlorouracil derivative generating a substitution adduct. Heating of his material in acetic anhydride affords the 5-(acetyloxy)pyrrolo[2,3-d]pyrimidine 9 in high yield. Base-mediated removal of the pyrrole protecting group gives free pyrrole 10 which is then glycosylated with 1-chloro-2-deoxy-3,5-ditoluoyl-alpha-D-erythro-pentofuranose (11) using the sodium salt method. The resulting glycosides 15a,b (alpha:beta, 1:4) are readily separated following hydrolysis of the C-5 acetyloxy group. The subsequently derived pure beta-5-(trifluoromethanesulfonyl) derivative 14 undergoes four types of palladium-catalyzed carbon-carbon bond-forming reactions and results in C-5 substituted compounds 15-18. An efficient synthetic route to the pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2'-deoxycadeguomycin (27), is presented. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidine-2,4-dione base portion in 15 into a protected 2-aminopyrrolo[2,3-d]pyrimidin-4-one 24. An alternative route to 27 was developed which involved prior conversion of the pyrrole-protected precursor 9 into its C-5 triflate derivative 20 followed by palladium-catalyzed carboxylation leading to ester 21. Removal of the pyrrole protecting group and then sodium salt-promoted glycosidation afforded the same beta-2'-deoxyribosyl intermediate 15 as prepared earlier. The stereochemistry of glycosidation was found to be dependent upon the electronic effect of the C-5 substituent on the pyrrole ring.

  DOI：

  10.1021/jo00121a027
• 作为产物：
  描述：

  1-(Benzyloxy)methyl-5-(methoxycarbonyl)-3-(methoxymethyl)-7-(p-nitrophenethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione 在 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 1-<(Benzyloxy)methyl>-7-<2'-deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione
  参考文献：
  名称：

  A New Synthetic Route to .beta.-2'-Deoxyribosyl-5-Substituted Pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-Deoxycadeguomycin

  摘要：

  A new and flexible synthetic route to beta-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines has been developed. Formation of the pyrrole ring is effected by combining sodium N-(4-nitrophenethyl)-glycinate with a differently protected 6-chlorouracil derivative generating a substitution adduct. Heating of his material in acetic anhydride affords the 5-(acetyloxy)pyrrolo[2,3-d]pyrimidine 9 in high yield. Base-mediated removal of the pyrrole protecting group gives free pyrrole 10 which is then glycosylated with 1-chloro-2-deoxy-3,5-ditoluoyl-alpha-D-erythro-pentofuranose (11) using the sodium salt method. The resulting glycosides 15a,b (alpha:beta, 1:4) are readily separated following hydrolysis of the C-5 acetyloxy group. The subsequently derived pure beta-5-(trifluoromethanesulfonyl) derivative 14 undergoes four types of palladium-catalyzed carbon-carbon bond-forming reactions and results in C-5 substituted compounds 15-18. An efficient synthetic route to the pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2'-deoxycadeguomycin (27), is presented. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidine-2,4-dione base portion in 15 into a protected 2-aminopyrrolo[2,3-d]pyrimidin-4-one 24. An alternative route to 27 was developed which involved prior conversion of the pyrrole-protected precursor 9 into its C-5 triflate derivative 20 followed by palladium-catalyzed carboxylation leading to ester 21. Removal of the pyrrole protecting group and then sodium salt-promoted glycosidation afforded the same beta-2'-deoxyribosyl intermediate 15 as prepared earlier. The stereochemistry of glycosidation was found to be dependent upon the electronic effect of the C-5 substituent on the pyrrole ring.

  DOI：

  10.1021/jo00121a027

文献信息

• Total synthesis of 2′-deoxycadeguomycin, a new pyrrolo[2,3-d]pyrimidine nucleotide analogue
  作者：Eric D. Edstrom、Yuan Wei

  DOI：10.1016/0040-4039(94)88407-2

  日期：1994.11

  This paper describes an efficient synthetic route to a novel pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2′-deoxycadeguomycin 4a. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidin-2,4-dione base portion in 1a into a protected 2-amino-pyrrolo[2,3-d]pyrimidin-4-one 3a.

  本文描述了一种新型的吡咯并[2,3- d ]嘧啶核苷酸类似物2'-deoxycadeguomycin 4a的有效合成途径。关键的转换涉及将1a中受差异保护的吡咯并[2,3 - d ]嘧啶-2,4-二酮基部分转化为受保护的2-氨基-吡咯并[2,3 - d ]嘧啶-4-酮3a。
• A New Efficient Route to 5-Substituted .beta.-2'-Deoxyribosylpyrrolo[2,3-d]pyrimidines. Palladium-Catalyzed Functionalizations of a C-5 Triflate Intermediate
  作者：Eric D. Edstrom、Yuan Wei

  DOI：10.1021/jo00102a011

  日期：1994.11

  An efficient synthesis of a beta-2'-deoxyribosyl-5 -[(trifluoromethanesulfonyl)oxy]pyrrolo[2,3-d]pyrimidine- 2,4-dione 9, starting from 6-chlorouracil, is presented along with its subsequent functionalization at C-5 using four types of palladium-catalyzed reactions.
• A New Synthetic Route to .beta.-2'-Deoxyribosyl-5-Substituted Pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-Deoxycadeguomycin
  作者：Eric D. Edstrom、Yuan Wei

  DOI：10.1021/jo00121a027

  日期：1995.8

  A new and flexible synthetic route to beta-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines has been developed. Formation of the pyrrole ring is effected by combining sodium N-(4-nitrophenethyl)-glycinate with a differently protected 6-chlorouracil derivative generating a substitution adduct. Heating of his material in acetic anhydride affords the 5-(acetyloxy)pyrrolo[2,3-d]pyrimidine 9 in high yield. Base-mediated removal of the pyrrole protecting group gives free pyrrole 10 which is then glycosylated with 1-chloro-2-deoxy-3,5-ditoluoyl-alpha-D-erythro-pentofuranose (11) using the sodium salt method. The resulting glycosides 15a,b (alpha:beta, 1:4) are readily separated following hydrolysis of the C-5 acetyloxy group. The subsequently derived pure beta-5-(trifluoromethanesulfonyl) derivative 14 undergoes four types of palladium-catalyzed carbon-carbon bond-forming reactions and results in C-5 substituted compounds 15-18. An efficient synthetic route to the pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2'-deoxycadeguomycin (27), is presented. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidine-2,4-dione base portion in 15 into a protected 2-aminopyrrolo[2,3-d]pyrimidin-4-one 24. An alternative route to 27 was developed which involved prior conversion of the pyrrole-protected precursor 9 into its C-5 triflate derivative 20 followed by palladium-catalyzed carboxylation leading to ester 21. Removal of the pyrrole protecting group and then sodium salt-promoted glycosidation afforded the same beta-2'-deoxyribosyl intermediate 15 as prepared earlier. The stereochemistry of glycosidation was found to be dependent upon the electronic effect of the C-5 substituent on the pyrrole ring.