[(2R)-3-[(2-chlorophenoxy)-[[(2R,3R,4S,5R)-5-[2-oxo-4-(4-oxopentanoylamino)pyrimidin-1-yl]-3,4-bis(4-oxopentanoyloxy)oxolan-2-yl]methoxy]phosphoryl]oxy-2-hexadecanoyloxypropyl] hexadecanoate | 197303-70-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: [(2R)-3-[(2-chlorophenoxy)-[[(2R,3R,4S,5R)-5-[2-oxo-4-(4-oxopentanoylamino)pyrimidin-1-yl]-3,4-bis(4-oxopentanoyloxy)oxolan-2-yl]methoxy]phosphoryl]oxy-2-hexadecanoyloxypropyl] hexadecanoate
• CAS: 197303-70-1
• 化学式: C₆₅H₁₀₁ClN₃O₁₈P
• 分子量: 1278.95
• InChiKey: INRAAOVPKYUMGX-IDTRHYCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.8
• 重原子数：
  88
• 可旋转键数：
  56
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  272
• 氢给体数：
  1
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  [(2R)-3-[(2-chlorophenoxy)-[[(2R,3R,4S,5R)-5-[2-oxo-4-(4-oxopentanoylamino)pyrimidin-1-yl]-3,4-bis(4-oxopentanoyloxy)oxolan-2-yl]methoxy]phosphoryl]oxy-2-hexadecanoyloxypropyl] hexadecanoate 在 一水合肼 作用下， 以 四氢呋喃 、 吡啶 、 水 为溶剂， 反应 4.5h， 生成 [(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(2R)-2,3-di(hexadecanoyloxy)propyl] phosphate;tributylazanium
  参考文献：
  名称：

  Synthesis of 1-β-d-arabinofuranosyl-cytosine 5′-phosphate-l-1,2-diacylglycerols

  摘要：

  5'-O-MMTr-cytosine arabinoside was prepared on a large scale from 5'-O-MMTr-cytidine with diphenyl carbonate via 5'-protected cytidine-2',3'-carbonate-ara-cytidine-2',2-anhydro derivative at a 67% yield. 1,2-Dipalmitoyl-sn-glycerol, 1,2-distearoyl-sn-glycerol and 1,2-dioleoyl-sn-glycerol were phosphorylated first with 2-chlorphenyl-phosphorobis-triazolide quantitatively (Welch and Chattopadhyaya, 1985. Acta Chem. Scand. B39, 47-57). This method was used in order to avoid acyl migration, then the glycerophosphate intermediates were condensed with 2',3',N-4-trileulinyl-1-beta-D-arabinofuranosylcytosine in the presence of 2-mesytilensulphonyl chloride (MSCI) and 1-methylimidazole (MeIm)-which was used in the coupling of nucleotides (Nyilas et al., 1986. Acta Chem. Scand. B40, 678-684)-in an 85-88% yield compared with the low yielding diester method of Ryu et al., 1982. J. Med. Chem. 25, 1322-1329. Deblocking was carried out in two steps with tetrabutylammonium fluoride (TBAF) and hydrazine hydrate, producing target compounds (9a, 9b, 9c) at a 50% yield. (C) 1997 Elsevier Science Ireland Ltd.

  DOI：

  10.1016/s0009-3084(97)00056-x
• 作为产物：
  描述：

  胞苷 在 吡啶 、 N-甲基咪唑 、 碳酸二苯酯 、 2,4,6-三甲基苯磺酰氯 、 碳酸氢钠 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.33h， 生成 [(2R)-3-[(2-chlorophenoxy)-[[(2R,3R,4S,5R)-5-[2-oxo-4-(4-oxopentanoylamino)pyrimidin-1-yl]-3,4-bis(4-oxopentanoyloxy)oxolan-2-yl]methoxy]phosphoryl]oxy-2-hexadecanoyloxypropyl] hexadecanoate
  参考文献：
  名称：

  An Improved Synthesis of 1-β-D-Arabinofuranosylcytosine 5′-Phosphate-L-1,2-diacylglycerols

  摘要：

  5'-O-MMTr-cytosine arabinoside was prepared on a large scale from 5'-0-MMTr-cytidine with diphenyl carbonate via 5'-protected cytidine - 2',3'-carbonate -- aracytidine-2',2-anhydro derivative at a 67 % yield. The synthesis of 1,2-L-dipalmitoyl-sn-glycerol, 1,2-L-distearoyl-sn-glycerol and 1,2-L-dioleoyl-sn-glycerol described here using 9-fluorenylmethoxycarbonyl (FMOC) group for protection of 3-position of glycerol which can be selectively removed by Et3N treatment on the overall 60-70 % yield based on 1,2,-isopropilidene-sn-glycerol. These glycerols were phosphorylated first with 2-chlorophenyl-phosphoro-bis-triazolide quantitatively(1) in order to avoid acyl migration, then the glycerophosphate intermediates were condensed with 2',3',N-4-trileulinyl-1-beta-D-arabinofuranosylcytosine in the presence of 2-mesytilenesulphonyl chloride (MsCl) and 1-methylimidazole (MeIm)- which was used in the coupling of nucleotides(2)- in an 85-95 % yield compared with the low yielding diester method of Ryu(3.) Deblocking was carried out in two steps with tetrabutylammonium fluoride (TBAF) and hydrazine hydrate, producing target compouns (14a, 14b, 14c) at a 50 % yield.

  DOI：

  10.1080/07328319808004734

文献信息

• An Improved Synthesis of 1-β-D-Arabinofuranosylcytosine 5′-Phosphate-L-1,2-diacylglycerols
  作者：Ágnes Nyilas

  DOI：10.1080/07328319808004734

  日期：1998.9

  5'-O-MMTr-cytosine arabinoside was prepared on a large scale from 5'-0-MMTr-cytidine with diphenyl carbonate via 5'-protected cytidine - 2',3'-carbonate -- aracytidine-2',2-anhydro derivative at a 67 % yield. The synthesis of 1,2-L-dipalmitoyl-sn-glycerol, 1,2-L-distearoyl-sn-glycerol and 1,2-L-dioleoyl-sn-glycerol described here using 9-fluorenylmethoxycarbonyl (FMOC) group for protection of 3-position of glycerol which can be selectively removed by Et3N treatment on the overall 60-70 % yield based on 1,2,-isopropilidene-sn-glycerol. These glycerols were phosphorylated first with 2-chlorophenyl-phosphoro-bis-triazolide quantitatively(1) in order to avoid acyl migration, then the glycerophosphate intermediates were condensed with 2',3',N-4-trileulinyl-1-beta-D-arabinofuranosylcytosine in the presence of 2-mesytilenesulphonyl chloride (MsCl) and 1-methylimidazole (MeIm)- which was used in the coupling of nucleotides(2)- in an 85-95 % yield compared with the low yielding diester method of Ryu(3.) Deblocking was carried out in two steps with tetrabutylammonium fluoride (TBAF) and hydrazine hydrate, producing target compouns (14a, 14b, 14c) at a 50 % yield.
• Synthesis of 1-β-d-arabinofuranosyl-cytosine 5′-phosphate-l-1,2-diacylglycerols
  作者：Ágnes Nyilas

  DOI：10.1016/s0009-3084(97)00056-x

  日期：1997.9

  5'-O-MMTr-cytosine arabinoside was prepared on a large scale from 5'-O-MMTr-cytidine with diphenyl carbonate via 5'-protected cytidine-2',3'-carbonate-ara-cytidine-2',2-anhydro derivative at a 67% yield. 1,2-Dipalmitoyl-sn-glycerol, 1,2-distearoyl-sn-glycerol and 1,2-dioleoyl-sn-glycerol were phosphorylated first with 2-chlorphenyl-phosphorobis-triazolide quantitatively (Welch and Chattopadhyaya, 1985. Acta Chem. Scand. B39, 47-57). This method was used in order to avoid acyl migration, then the glycerophosphate intermediates were condensed with 2',3',N-4-trileulinyl-1-beta-D-arabinofuranosylcytosine in the presence of 2-mesytilensulphonyl chloride (MSCI) and 1-methylimidazole (MeIm)-which was used in the coupling of nucleotides (Nyilas et al., 1986. Acta Chem. Scand. B40, 678-684)-in an 85-88% yield compared with the low yielding diester method of Ryu et al., 1982. J. Med. Chem. 25, 1322-1329. Deblocking was carried out in two steps with tetrabutylammonium fluoride (TBAF) and hydrazine hydrate, producing target compounds (9a, 9b, 9c) at a 50% yield. (C) 1997 Elsevier Science Ireland Ltd.