(E)-(3S,6R,10S,16S)-10-(3-Chloro-4-methoxy-benzyl)-3-isobutyl-6-methyl-16-((E)-(R)-1-methyl-3-phenyl-allyl)-1,4-dioxa-8,11-diaza-cyclohexadec-13-ene-2,5,9,12-tetraone | 162679-35-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (E)-(3S,6R,10S,16S)-10-(3-Chloro-4-methoxy-benzyl)-3-isobutyl-6-methyl-16-((E)-(R)-1-methyl-3-phenyl-allyl)-1,4-dioxa-8,11-diaza-cyclohexadec-13-ene-2,5,9,12-tetraone
• 英文别名: Cryptophycin 46；(3S,6R,10S,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[(E,2R)-4-phenylbut-3-en-2-yl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
• CAS: 162679-35-8
• 化学式: C₃₅H₄₃ClN₂O₇
• 分子量: 639.189
• InChiKey: QLGFKEFRTAOKJU-FDUWFYLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-(3S,6R,10S,16S)-10-(3-Chloro-4-methoxy-benzyl)-3-isobutyl-6-methyl-16-((E)-(R)-1-methyl-3-phenyl-allyl)-1,4-dioxa-8,11-diaza-cyclohexadec-13-ene-2,5,9,12-tetraone 在 盐酸 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 100.0h， 生成 cryptophycin-9
  参考文献：
  名称：

  Total Structures of Cryptophycins, Potent Antitumor Depsipeptides from the Blue-Green Alga Nostoc sp. Strain GSV 224

  摘要：

  Cryptophycin (A,1), the major cytotoxin in the blue-green alga (cyanobacterium) Nostoc sp. GSV 224, shows excellent activity against solid tumors implanted in mice. This cyclic depsipeptide had previously been isolated from Nostoc sp. ATCC 53789 as an antifungal agent and its gross structure determined by researchers at Merck. The relative and absolute stereochemistry of this potentially important drug has now been established using a combination of chemical and spectral techniques. Six minor cryptophycins (B-G, 2-7) have also been isolated from GSV 224 and their total structures and cytotoxicities determined. Two types of cryptophycins are present in this alga, the major series possessing a monochlorinated L-O-methyltyrosine unit and the minor series possessing a nonchlorinated D-O-methyltyrosine unit. Structure-activity relationship (SAR) studies of the cryptophycins and several derivatives and degradation products (8-14) are described. Also presented are preliminary in vivo results far cryptophycin A against six solid tumors.

  DOI：

  10.1021/ja00090a020
• 作为产物：
  描述：

  (S)-2-((R)-3-Amino-2-methyl-propionyloxy)-4-methyl-pentanoic acid (E)-(1S,2R)-1-{(E)-3-[(S)-1-carboxy-2-(4-methoxy-phenyl)-ethylcarbamoyl]-allyl}-2-methyl-4-phenyl-but-3-enyl ester 在 五氟苯基二苯基磷酸酯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以62%的产率得到(E)-(3S,6R,10S,16S)-10-(3-Chloro-4-methoxy-benzyl)-3-isobutyl-6-methyl-16-((E)-(R)-1-methyl-3-phenyl-allyl)-1,4-dioxa-8,11-diaza-cyclohexadec-13-ene-2,5,9,12-tetraone
  参考文献：
  名称：

  隐藻素的全合成。隐藻素 A 和 C 结构的修订

  摘要：

  描述了隐霉素 C 和 D 的收敛全合成。已经表明，在两种天然产物中，α-氨基酸的绝对构型对应于 D 系列。已更正了隐藻素 C 的结构分配以反映这一事实。由于隐藻素A的结构与隐藻素C相关，隐藻素A中的氯-0-甲基酪氨酸单元具有D-构型。隐藻素是与陆生蓝绿藻 Nostoc sp. 相关的强效肿瘤选择性细胞毒素。GSV 224' 和 Nostoc sp。ATCC 53789.2 每种藻类中的主要细胞毒素，cryptophycin A，对植入小鼠的实体瘤（包括耐药性肿瘤）显示出极好的活性。超过 20 种相关的细胞毒素作为次要成分存在于 GSV 224 菌株中，以及这些化合物中的一些，例如，隐藻素 B 和 C，已被分离出足够的量用于体内评估。~为了获得足够数量的选定天然存在的隐藻素和合成类似物，用于构效关系 (SAR) 研究、临床前评估和人类临床试验，我们设计了一个通用的合成。正如原始论文中所述，Cryptophycins

  DOI：

  10.1021/ja00114a011

文献信息

• Total Synthesis of Cryptophycins. Revision of the Structures of Cryptophycins A and C
  作者：Russell A. Barrow、Thomas Hemscheidt、Jian Liang、Seunguk Paik、Richard E. Moore、Marcus A. Tius

  DOI：10.1021/ja00114a011

  日期：1995.3

  The convergent total synthesis of cryptophycins C and D is described. It has been shown that in both natural products the absolute configuration of the a-amino acid corresponds to the D-series. The structural assignment for cryptophycin C has been corrected to reflect this fact. Since the structure of cryptophycin A has been correlated to cryptophycin C, the chloro-0-methyltyrosine unit in cryptophycin

  描述了隐霉素 C 和 D 的收敛全合成。已经表明，在两种天然产物中，α-氨基酸的绝对构型对应于 D 系列。已更正了隐藻素 C 的结构分配以反映这一事实。由于隐藻素A的结构与隐藻素C相关，隐藻素A中的氯-0-甲基酪氨酸单元具有D-构型。隐藻素是与陆生蓝绿藻 Nostoc sp. 相关的强效肿瘤选择性细胞毒素。GSV 224' 和 Nostoc sp。ATCC 53789.2 每种藻类中的主要细胞毒素，cryptophycin A，对植入小鼠的实体瘤（包括耐药性肿瘤）显示出极好的活性。超过 20 种相关的细胞毒素作为次要成分存在于 GSV 224 菌株中，以及这些化合物中的一些，例如，隐藻素 B 和 C，已被分离出足够的量用于体内评估。~为了获得足够数量的选定天然存在的隐藻素和合成类似物，用于构效关系 (SAR) 研究、临床前评估和人类临床试验，我们设计了一个通用的合成。正如原始论文中所述，Cryptophycins
• Total Structures of Cryptophycins, Potent Antitumor Depsipeptides from the Blue-Green Alga Nostoc sp. Strain GSV 224
  作者：Golakoti Trimurtulu、Ikuko Ohtani、Gregory M. L. Patterson、Richard E. Moore、Thomas H. Corbett、Frederick A. Valeriote、Lisa Demchik

  DOI：10.1021/ja00090a020

  日期：1994.6

  Cryptophycin (A,1), the major cytotoxin in the blue-green alga (cyanobacterium) Nostoc sp. GSV 224, shows excellent activity against solid tumors implanted in mice. This cyclic depsipeptide had previously been isolated from Nostoc sp. ATCC 53789 as an antifungal agent and its gross structure determined by researchers at Merck. The relative and absolute stereochemistry of this potentially important drug has now been established using a combination of chemical and spectral techniques. Six minor cryptophycins (B-G, 2-7) have also been isolated from GSV 224 and their total structures and cytotoxicities determined. Two types of cryptophycins are present in this alga, the major series possessing a monochlorinated L-O-methyltyrosine unit and the minor series possessing a nonchlorinated D-O-methyltyrosine unit. Structure-activity relationship (SAR) studies of the cryptophycins and several derivatives and degradation products (8-14) are described. Also presented are preliminary in vivo results far cryptophycin A against six solid tumors.