cryptophycin-26 | 168482-38-0

• 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: cryptophycin-26
• 英文别名: Cryptophycin 26；(3S,6R,10R,14R)-10-[(3-chloro-4-methoxyphenyl)methyl]-14-[(E,2S,3R)-2-hydroxy-3-methyl-5-phenylpent-4-enyl]-6-methyl-3-(2-methylpropyl)-1,4-dioxa-8,11-diazacyclotetradecane-2,5,9,12-tetrone
• CAS: 168482-38-0
• 化学式: C₃₅H₄₅ClN₂O₈
• 分子量: 657.204
• InChiKey: JVTODUXHSHCQOJ-VYCCHRMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  cryptophycin-26 在 吡啶 、 氢溴酸 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 对甲苯磺酰氯 作用下， 以 乙二醇二甲醚 为溶剂， 反应 103.0h， 生成 cryptophycin 3
  参考文献：
  名称：

  Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224

  摘要：

  Using a modified isolation procedure devoid of methanol, 18 new cyclic cryptophycins have been isolated from Nostoc sp. GSV 224 as minor constituents in addition to cryptophycins-1 (A), -2 (B), -3 (C), and -4 (D). Acyclic cryptophycins are not found, indicating that the previously reported cryptophycins-5 (E methyl ester), -6 (F methyl ester), and -7 (G) are artifacts produced as a consequence of using methanol in the isolation scheme. Seventeen of the new cyclic analogs differ in structure in either one of the two hydroxy acid units, viz. unit A [(5S,6S,7R,8R)-7,8-epoxy-5-hydroxy-6-methyl-8-phenyl-2(E)-octenoic acid for cryptophycin-1 or (5S,6S)-5-hydroxy-6-methyl-8-phenyl-2(E),7(E)-octadienoic acid for cryptophycin-3] and unit D [(2S)-2-hydroxy-4-methylvaleric acid], or one of the two amino acid units, viz. unit B [(2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid] and unit C [(2R)3-amino-2-methylpropionic acid], found in the cyclic ABCD peptolide. In unit A of cryptophycins-26, -28, -30, and -40, the methyl group on C-6 is missing or the Delta(2)-double bond is hydrated. In unit B of cryptophycins-16, -17, -23, 31, -43, and -45, the aromatic ring is phenolic and/or possesses two or zero chlorines. In unit C of cryptophycins-21 and -29, the methyl group on C-2 is missing. In unit D of cryptophycins-18, -19, -49, -50, and -54, a different alkyl group (propyl, isopropyl, or sec-butyl) is attached to C-2. Only one of the new analogs, cryptophycin-24, differs in structure for two units by lacking chlorine in unit B and the methyl group in unit C. Revised structures are presented for cryptophycins-5, -6, and -7 and are correlated with cryptophycin-3, the relative stereochemistry of which has been further rigorously established by X-ray crystallography. NOE studies show that the preferred conformations of most cryptophycins in solution differ from the conformation of cryptophycin-3 in the crystal state. Although cryptophycin-1 is relatively stable at pH 7, both in ionic and nonionic media, the ester bond linking units C and D is fairly labile to solvolysis and mild base hydrolysis. Structure-activity relationship studies indicate that the intact macrolide ring, the epoxide group, the chloro and 0-methyl groups in unit B, and the methyl group in unit C are needed for the in vivo activity of cryptophycin-1.

  DOI：

  10.1021/ja00154a002
• 作为产物：
  描述：

  cryptophycin-30 在 吡啶 、 氯化亚砜 作用下， 反应 72.0h， 以0.2 mg的产率得到cryptophycin-26
  参考文献：
  名称：

  Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224

  摘要：

  Using a modified isolation procedure devoid of methanol, 18 new cyclic cryptophycins have been isolated from Nostoc sp. GSV 224 as minor constituents in addition to cryptophycins-1 (A), -2 (B), -3 (C), and -4 (D). Acyclic cryptophycins are not found, indicating that the previously reported cryptophycins-5 (E methyl ester), -6 (F methyl ester), and -7 (G) are artifacts produced as a consequence of using methanol in the isolation scheme. Seventeen of the new cyclic analogs differ in structure in either one of the two hydroxy acid units, viz. unit A [(5S,6S,7R,8R)-7,8-epoxy-5-hydroxy-6-methyl-8-phenyl-2(E)-octenoic acid for cryptophycin-1 or (5S,6S)-5-hydroxy-6-methyl-8-phenyl-2(E),7(E)-octadienoic acid for cryptophycin-3] and unit D [(2S)-2-hydroxy-4-methylvaleric acid], or one of the two amino acid units, viz. unit B [(2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid] and unit C [(2R)3-amino-2-methylpropionic acid], found in the cyclic ABCD peptolide. In unit A of cryptophycins-26, -28, -30, and -40, the methyl group on C-6 is missing or the Delta(2)-double bond is hydrated. In unit B of cryptophycins-16, -17, -23, 31, -43, and -45, the aromatic ring is phenolic and/or possesses two or zero chlorines. In unit C of cryptophycins-21 and -29, the methyl group on C-2 is missing. In unit D of cryptophycins-18, -19, -49, -50, and -54, a different alkyl group (propyl, isopropyl, or sec-butyl) is attached to C-2. Only one of the new analogs, cryptophycin-24, differs in structure for two units by lacking chlorine in unit B and the methyl group in unit C. Revised structures are presented for cryptophycins-5, -6, and -7 and are correlated with cryptophycin-3, the relative stereochemistry of which has been further rigorously established by X-ray crystallography. NOE studies show that the preferred conformations of most cryptophycins in solution differ from the conformation of cryptophycin-3 in the crystal state. Although cryptophycin-1 is relatively stable at pH 7, both in ionic and nonionic media, the ester bond linking units C and D is fairly labile to solvolysis and mild base hydrolysis. Structure-activity relationship studies indicate that the intact macrolide ring, the epoxide group, the chloro and 0-methyl groups in unit B, and the methyl group in unit C are needed for the in vivo activity of cryptophycin-1.

  DOI：

  10.1021/ja00154a002

文献信息

• Method for modifying microcystins and nodularins
  申请人：Cyano Biotech GmbH

  公开号：US11124818B2

  公开（公告）日：2021-09-21

  A method is used for producing a modified non-ribosomal peptide, e.g. a modified microcystin and/or modified nodularin (together CA), including the steps of: a) growing a modified non-ribosomal peptide producing cyanobacteria strain in a culture media, h) adding one or more modified substrates, preferably modified amino acids to said culture, and c) inoculating the non-ribosomal peptide, producing strain the presence of said modified substrates. The thus modified non-ribosomal peptide may be used for the therapy of various diseases.

  一种用于生产改性非核糖体肽的方法，例如改性微囊藻毒素和/或改性球藻毒素（合称 CA），包括以下步骤：a) 在培养基中培养产生改性非核糖体肽的蓝藻菌株；h) 向所述培养基中添加一种或多种改性底物，最好是改性氨基酸；以及 c) 接种非核糖体肽，产生存在所述改性底物的菌株。这样修饰的非核糖体肽可用于治疗各种疾病。
• METHOD FOR MODIFYING MICROCYSTINS AND NODULARINS
  申请人：Cyano Biotech GmbH

  公开号：US20200377922A1

  公开（公告）日：2020-12-03

  A method is used for producing a modified non-ribosomal peptide, e.g. a modified microcystin and/or modified nodularin (together CA), including the steps of a) growing a modified non-ribosomal peptide producing cyanobacteria strain in a culture media, b) adding one or more modified substrates, preferably modified amino acids to said culture, and c) inoculating the non-ribosomal peptide, producing strain the presence of said modified substrates. The thus modified non-ribosomal peptide may be used for the therapy of various diseases.
• Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224
  作者：Trimurtulu Golakoti、Junichi Ogino、Carl E. Heltzel、Trang Le Husebo、Craig M. Jensen、Linda K. Larsen、Gregory M. L. Patterson、Richard E. Moore、Susan L. Mooberry、Thomas H. Corbett、Frederick A. Valeriote

  DOI：10.1021/ja00154a002

  日期：1995.12.1

  Using a modified isolation procedure devoid of methanol, 18 new cyclic cryptophycins have been isolated from Nostoc sp. GSV 224 as minor constituents in addition to cryptophycins-1 (A), -2 (B), -3 (C), and -4 (D). Acyclic cryptophycins are not found, indicating that the previously reported cryptophycins-5 (E methyl ester), -6 (F methyl ester), and -7 (G) are artifacts produced as a consequence of using methanol in the isolation scheme. Seventeen of the new cyclic analogs differ in structure in either one of the two hydroxy acid units, viz. unit A [(5S,6S,7R,8R)-7,8-epoxy-5-hydroxy-6-methyl-8-phenyl-2(E)-octenoic acid for cryptophycin-1 or (5S,6S)-5-hydroxy-6-methyl-8-phenyl-2(E),7(E)-octadienoic acid for cryptophycin-3] and unit D [(2S)-2-hydroxy-4-methylvaleric acid], or one of the two amino acid units, viz. unit B [(2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid] and unit C [(2R)3-amino-2-methylpropionic acid], found in the cyclic ABCD peptolide. In unit A of cryptophycins-26, -28, -30, and -40, the methyl group on C-6 is missing or the Delta(2)-double bond is hydrated. In unit B of cryptophycins-16, -17, -23, 31, -43, and -45, the aromatic ring is phenolic and/or possesses two or zero chlorines. In unit C of cryptophycins-21 and -29, the methyl group on C-2 is missing. In unit D of cryptophycins-18, -19, -49, -50, and -54, a different alkyl group (propyl, isopropyl, or sec-butyl) is attached to C-2. Only one of the new analogs, cryptophycin-24, differs in structure for two units by lacking chlorine in unit B and the methyl group in unit C. Revised structures are presented for cryptophycins-5, -6, and -7 and are correlated with cryptophycin-3, the relative stereochemistry of which has been further rigorously established by X-ray crystallography. NOE studies show that the preferred conformations of most cryptophycins in solution differ from the conformation of cryptophycin-3 in the crystal state. Although cryptophycin-1 is relatively stable at pH 7, both in ionic and nonionic media, the ester bond linking units C and D is fairly labile to solvolysis and mild base hydrolysis. Structure-activity relationship studies indicate that the intact macrolide ring, the epoxide group, the chloro and 0-methyl groups in unit B, and the methyl group in unit C are needed for the in vivo activity of cryptophycin-1.