(3aR,6R,7S,8R,12aR)-12-[1-[1,3]Dioxolan-2-yl-meth-(E)-ylidene]-7,8-dihydroxy-6,7,8-trimethyl-5,9-dioxo-decahydro-4,10-dioxa-1-aza-cyclopentacycloundecene-1-carboxylic acid 4,5-dimethoxy-2-nitro-benzyl ester | 225640-36-8

• 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: (3aR,6R,7S,8R,12aR)-12-[1-[1,3]Dioxolan-2-yl-meth-(E)-ylidene]-7,8-dihydroxy-6,7,8-trimethyl-5,9-dioxo-decahydro-4,10-dioxa-1-aza-cyclopentacycloundecene-1-carboxylic acid 4,5-dimethoxy-2-nitro-benzyl ester
• CAS: 225640-36-8
• 化学式: C₂₈H₃₆N₂O₁₄
• 分子量: 624.599
• InChiKey: ZHVCFFVVXSHZIL-DBLYNCQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.23
• 重原子数：
  44.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  202.66
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  (3aR,6R,7S,8R,12aR)-12-[1-[1,3]Dioxolan-2-yl-meth-(E)-ylidene]-7,8-dihydroxy-6,7,8-trimethyl-5,9-dioxo-decahydro-4,10-dioxa-1-aza-cyclopentacycloundecene-1-carboxylic acid 4,5-dimethoxy-2-nitro-benzyl ester 在 盐酸 、 potassium cyanide 、 aluminum oxide 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 (2R,3R)-3-Carbamoyloxy-2-((E)-1-carbamoyloxymethyl-3-oxo-propenyl)-pyrrolidine-1-carboxylic acid 4,5-dimethoxy-2-nitro-benzyl ester
  参考文献：
  名称：

  DNA cross-linking by a phototriggered pyrrolic progenitor developed from monocrotaline

  摘要：

  A wide variety of pyrrolizidine alkaloids, such as monocrotaline, exert their cytotoxicity through the formation of DNA-DNA interstrand cross-links and DNA-protein cross-links. These pyrrolizidine alkaloids are oxidatively activated in vivo forming a highly reactive pyrrolic-type intermediate, which is responsible for the DNA cross-Linking reaction. The oxidative pathway of activation leads to undesired toxicity. Based on a previously reported photochemically triggered progenitor of monocrotaline, we describe here the semi-synthesis and DNA cross-linking of a dicarbamate analogue of the original phototriggered progenitor. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01341-7
• 作为产物：
  描述：

  12-[1,3]dioxolan-2-ylmethylene-7,8-dihydroxy-6,7,8-trimethyl-5,9-dioxo-decahydro-4,10-dioxa-1-aza-cyclopentacycloundecene-1-carboxylic acid 9H-fluoren-9-ylmethyl ester 在 哌啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (3aR,6R,7S,8R,12aR)-12-[1-[1,3]Dioxolan-2-yl-meth-(E)-ylidene]-7,8-dihydroxy-6,7,8-trimethyl-5,9-dioxo-decahydro-4,10-dioxa-1-aza-cyclopentacycloundecene-1-carboxylic acid 4,5-dimethoxy-2-nitro-benzyl ester
  参考文献：
  名称：

  DNA cross-linking by a phototriggered pyrrolic progenitor developed from monocrotaline

  摘要：

  A wide variety of pyrrolizidine alkaloids, such as monocrotaline, exert their cytotoxicity through the formation of DNA-DNA interstrand cross-links and DNA-protein cross-links. These pyrrolizidine alkaloids are oxidatively activated in vivo forming a highly reactive pyrrolic-type intermediate, which is responsible for the DNA cross-Linking reaction. The oxidative pathway of activation leads to undesired toxicity. Based on a previously reported photochemically triggered progenitor of monocrotaline, we describe here the semi-synthesis and DNA cross-linking of a dicarbamate analogue of the original phototriggered progenitor. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01341-7

文献信息

• DNA Cross-Linking by a Phototriggered Dehydromonocrotaline Progenitor
  作者：Jetze J. Tepe、Robert M. Williams

  DOI：10.1021/ja983894k

  日期：1999.4.1

  A wide variety of pyrrolizidine alkaloids, such as monocrotaline, and the clinically significant mitomycins and the related FR-900482, FK 973, and FR-66979 exert their cytotoxicity through the formation of DNA−DNA interstrand cross-links and DNA−protein cross-links. These naturally occurring antitumor antibiotics are generally either oxidatively or reductively activated in vivo forming a highly reactive

  多种吡咯里西啶生物碱，如野百合碱、具有临床意义的丝裂霉素和相关的 FR-900482、FK 973 和 FR-66979，通过形成 DNA-DNA 链间交联和 DNA-蛋白质交联发挥其细胞毒性。链接。这些天然存在的抗肿瘤抗生素通常在体内被氧化或还原激活，形成高反应性的吡咯型中间体，它负责最终的 DNA 交联反应。然而，这些氧化和还原途径通常会导致各种不良的毒性事件。随着对新的和细胞毒性较小的抗肿瘤药物的需求不断增加，以及最近具有临床意义的光分离技术的成功，