N^α-((tert-butyloxy)carbonyl)-N^β-<1-amino-3(S)-(6-amino-4-(ethoxycarbonyl)-5-methylpyrimidin-2-yl)propion-3-yl>-(S)-β-aminoalanine amide | 75624-28-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N^α-((tert-butyloxy)carbonyl)-N^β-<1-amino-3(S)-(6-amino-4-(ethoxycarbonyl)-5-methylpyrimidin-2-yl)propion-3-yl>-(S)-β-aminoalanine amide
• 英文别名: N^α-(tert-butoxycarbonyl)-N^β-<1-amino-3-(4-amino-6-carbethoxy-5-methylpyrimidin-2-yl)propion-3-yl>-(S)-β-aminoalanineamide；ethyl 6-amino-2-[(1S)-3-amino-1-[[(2S)-3-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carboxylate
• CAS: 75624-28-1
• 化学式: C₁₉H₃₁N₇O₆
• 分子量: 453.498
• InChiKey: VEIMDCBHHLCICT-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.57
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  214.64
• 氢给体数：
  5.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N^α-((tert-butyloxy)carbonyl)-N^β-<1-amino-3(S)-(6-amino-4-(ethoxycarbonyl)-5-methylpyrimidin-2-yl)propion-3-yl>-(S)-β-aminoalanine amide 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.5h， 以91%的产率得到pyrimidoblamic acid
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 2. Synthesis of (-)-Pyrimidoblamic Acid, epi-(+)-Pyrimidoblamic Acid, (+)-Desacetamidopyrimidoblamic Acid, and (-)-Descarboxamidopyrimidoblamic Acid

  摘要：

  Full details of concise syntheses of (-)-pyrimidoblamic acid (1), the authentic heterocyclic core of the bleomycin A(2) metal binding domain, as well as the key substructure analogs epi-(+)-pyrimidoblamic acid (2), (+)-desacetamidopyrimidoblamic acid (3), and (-)-descarboxamidppyrimidoblamic acid (4) are described. Key to the approach is the implementation of an inverse electron demand [4 + 2] cycloaddition reaction of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine with 1-(dibenzylamino)-1-propyne or in situ generated 1,1-diaminopropene for the one-step preparation of an appropriately functionalized pyrimidine nucleus. The development and subsequent implementation of a diastereoselective imine addition reaction of optically active N-acyloxazolidinone enolates provided a stereocontrolled introduction of the pyrimidoblamic acid C2 acetamido side chain. Chemical studies which unambiguously establish and confirm the absolute configuration of the C2 acetamido side chain are detailed, and their extension to the synthesis of (-)-descarboxamidopyrimidoblamic acid (4) is described.

  DOI：

  10.1021/ja00092a012
• 作为产物：
  描述：

  1,3,5-三嗪-2,4,6-三甲酸三乙酯 在 manganese(IV) oxide 、 sodium tetrahydroborate 、 tin(II) trifluoromethanesulfonate 、 偶氮二异丁腈 、 乙醇 、 三氟甲磺酸 、 4 A molecular sieve 、 氨 、 三正丁基氢锡 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 91.25h， 生成 N^α-((tert-butyloxy)carbonyl)-N^β-<1-amino-3(S)-(6-amino-4-(ethoxycarbonyl)-5-methylpyrimidin-2-yl)propion-3-yl>-(S)-β-aminoalanine amide
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 2. Synthesis of (-)-Pyrimidoblamic Acid, epi-(+)-Pyrimidoblamic Acid, (+)-Desacetamidopyrimidoblamic Acid, and (-)-Descarboxamidopyrimidoblamic Acid

  摘要：

  Full details of concise syntheses of (-)-pyrimidoblamic acid (1), the authentic heterocyclic core of the bleomycin A(2) metal binding domain, as well as the key substructure analogs epi-(+)-pyrimidoblamic acid (2), (+)-desacetamidopyrimidoblamic acid (3), and (-)-descarboxamidppyrimidoblamic acid (4) are described. Key to the approach is the implementation of an inverse electron demand [4 + 2] cycloaddition reaction of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine with 1-(dibenzylamino)-1-propyne or in situ generated 1,1-diaminopropene for the one-step preparation of an appropriately functionalized pyrimidine nucleus. The development and subsequent implementation of a diastereoselective imine addition reaction of optically active N-acyloxazolidinone enolates provided a stereocontrolled introduction of the pyrimidoblamic acid C2 acetamido side chain. Chemical studies which unambiguously establish and confirm the absolute configuration of the C2 acetamido side chain are detailed, and their extension to the synthesis of (-)-descarboxamidopyrimidoblamic acid (4) is described.

  DOI：

  10.1021/ja00092a012

文献信息

• Boger, Dale L.; Menezes, Royce F.; Honda, Takeshi, Angewandte Chemie, 1993, vol. 105, # 2, p. 310 - 311
  作者：Boger, Dale L.、Menezes, Royce F.、Honda, Takeshi

  DOI：——

  日期：——
• Synthesis of the pyrimidine moieties of bleomycin and epi-bleomycin
  作者：Heihachiro Arai、William K. Hagmann、H. Suguna、Sidney M. Hecht

  DOI：10.1021/ja00541a074

  日期：1980.10
• Synthesis of pyrimidoblamic acid and epipyrimidoblamic acid
  作者：Yoshiaki Aoyagi、Mukund S. Chorghade、Abeysinghe A. Padmapriya、Hosbett Suguna、Sidney M. Hecht

  DOI：10.1021/jo00313a016

  日期：1990.12

  The N-protected pyrimidine moieties of bleomycin (pyrimidoblamic acid, 1) and epibleomycin are reported. In addition to a complete description of a synthetic route outlined earlier (Arai, H.; Hagmann, W. K.; Suguna, H.; Hecht, S. M. J. Am. Chem. Soc 1980, 102,6631), a new route is also presented that provides access to multigram qauantities of pyrimidoblamic acid. Because bleomycin and epibleomycin, which differ only in the orientation of the propionamide substituent, differ significantly in their Cu(II) chelation and DNA cleavage properties, we also prepared an analogue of pyrimidoblamic acid lacking the proprionamide moiety.
• AOYAGI, YOSHIAKI;CHORGHADE, MUKUND S.;PADMAPRIYA, ABEYSINGLE A.;SUGUNA, H+, J. ORG. CHEM., 55,(1990) N6, C. 6291-6298
  作者：AOYAGI, YOSHIAKI、CHORGHADE, MUKUND S.、PADMAPRIYA, ABEYSINGLE A.、SUGUNA, H+

  DOI：——

  日期：——