Boc-epipyrimidoblamic acid | 96922-00-8

• 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: Boc-epipyrimidoblamic acid
• 英文别名: N^α-((tert-butyloxy)carbonyl)-N^β-<1-amino-3(R)-(6-amino-4-carboxy-5-methylpyrimidin-2-yl)propion-3-yl>-(S)-β-aminoalanine amide；N^α-tert-Butyloxycarbonyl-epi-(+)-pyrimidoblamsaeure；epipyrimidoblamic acid；6-amino-2-[(1R)-3-amino-1-[[(2S)-3-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carboxylic acid
• CAS: 96922-00-8
• 化学式: C₁₇H₂₇N₇O₆
• 分子量: 425.445
• InChiKey: XVCYESGSBIEXAS-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.05
• 重原子数：
  30.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  225.64
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  Boc-epipyrimidoblamic acid 在 盐酸 、 乙酸乙酯 作用下， 反应 1.0h， 以100%的产率得到epi-(+)-pyrimidoblamic acid hydrochloride
  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：

  2,4-dis(ethoxycarbonyl)-6-(N,N-dibenzylamino)-5-methylpyrimidine 在 manganese(IV) oxide 、 lithium hydroxide 、 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 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 71.75h， 生成 Boc-epipyrimidoblamic 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

文献信息

• Synthetic studies on an antitumor antibiotic, bleomycin. XIV. The synthesis of Boc-pyrimidoblamic acid.
  作者：MASAMI OTSUKA、MASATOSHI NARITA、MAKOTO YOSHIDA、SUSUMU KOBAYASHI、MASAJI OHNO、YOJI UMEZAWA、HAJIME MORISHIMA、SEIICHI SAITO、TOMOHISA TAKITA、HAMAO UMEZAWA

  DOI：10.1248/cpb.33.520

  日期：——

  New methodology was developed for the introduction of an acetate unit into the Schiff base 2, based on the reaction of the Schiff base 2 with malonic acid monoester or vinyloxyborane. Furthermore, the synthesis of Boc-pyrimidoblamic acid, a key fragment for the total synthesis of bleomycin, was achieved by utilizing these two methods.

  在希夫碱 2 与丙二酸单酯或乙烯氧基硼烷反应的基础上，开发了将醋酸单元引入希夫碱 2 的新方法。此外，还利用这两种方法合成了 Boc-嘧啶基氨基甲酸，它是全合成博来霉素的关键片段。
• 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 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.
• Boger, Dale L.; Honda, Takeshi; Menezes, Royce F., Journal of the American Chemical Society, 1994, vol. 116, # 13, p. 5631 - 5646
  作者：Boger, Dale L.、Honda, Takeshi、Menezes, Royce F.、Colletti, Steven L.

  DOI：——

  日期：——
• 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：——