cryptophycin-27 | 168569-15-1

• 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-27
• 英文别名: Cryptophycin 21；(3S,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
• CAS: 168569-15-1
• 化学式: C₃₄H₄₁ClN₂O₈
• 分子量: 641.161
• InChiKey: ATKRDMWWPRZLSY-BJJCRNJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  cryptophycin-27 在 二氯二茂钛 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以5 mg的产率得到cryptophycin-29
  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：

  2-{[{2-[(4-硝基苯基)磺酰]肼基<联氨基>}(羰基)乙酰基]氨基}苯甲酸 在 盐酸 、 lithium chloride 作用下， 以 乙二醇二甲醚 、 丙酮 为溶剂， 反应 92.0h， 生成 cryptophycin-27
  参考文献：
  名称：

  Isolation and Structure Determination of Cryptophycins 38, 326, and 327 from the Terrestrial Cyanobacterium Nostoc sp. GSV 224

  摘要：

  Cryptophycin-38 (2), -326 (3), and -327 (4) are three new trace constituents of the terrestrial cyanobacterium Nostoc sp. GSV 224. Cryptophycin-38 is a stereoisomer of cryptophycin-1 (1) and to date is the only naturally occurring analogue that possesses a SS epoxide group in unit A. Cryptophycin-327 is a geometric isomer that differs from 1 in having a cis Delta(2)-double bond in unit A. Cryptophycin-326 is related to cryptophycin-21, but has two chlorines ortho to the methoxy group in unit B. The relative and absolute stereochemistries of 2 have been related to known cryptophycins by semisynthesis and/or spectral analysis.

  DOI：

  10.1021/np0499665

文献信息

• Di-substituted maleic amide linker for antibody drug conjugating and preparation method and use thereof
  申请人：Mabwell (shanghai) Bioscience Co., Ltd.

  公开号：US10987430B2

  公开（公告）日：2021-04-27

  Provided in the present invention are a di-substituted maleic amide linker conjugated to an antibody and a preparation method and use thereof. In particular, the present invention conjugates a strongly cytotoxic active substance to a biomacromolecule through a class of new linkers. The class of linkers can selectively act simultaneously with disulphide chains, so as to greatly improve the substance homogeneity of a conjugate. The conjugate prepared by the linker of the present invention has a high inhibitory activity on a cell strain expressing the corresponding antigen. Also provided is a method for preparing the above-mentioned conjugate and the use.

  本发明提供了一种二取代马来酰胺连接物与抗体结合的制备方法及其用途。具体而言，本发明通过一类新连接物将一种强烈细胞毒活性物质与生物大分子结合。这类连接物可以与二硫键同时选择性地作用，从而极大地提高结合物质的均一性。本发明连接物制备的结合物对表达相应抗原的细胞株具有高抑制活性。还提供了制备上述结合物的方法和用途。
• Cryptophycins
  申请人：The University of Hawaii

  公开号：US05955423A1

  公开（公告）日：1999-09-21

  A cryptophycin compound is provided having the structure: ##STR1## Further provided are methods for producing novel cryptophycins from the Nostoc sp. of blue-green algae (cyanobacteria). Pharmaceutical compositions comprising novel cryptophycins are also provided, as are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells. Further provided are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells with drug resistant phenotypes, and to treat pathological conditions, such as neoplasia.

  提供了一种具有以下结构的cryptophycin化合物：##STR1## 进一步提供了从蓝藻（蓝细菌）Nostoc sp.中产生新的cryptophycins的方法。还提供了包含新的cryptophycins的制药组合物，以及使用cryptophycins来抑制高增殖细胞的增殖的方法。还提供了使用cryptophycins来抑制具有耐药表型的高增殖细胞的增殖，并治疗病理状况，例如肿瘤的方法。
• MACROCYCLIZATION OF COMPOUNDS FROM SOLID SUPPORT USING THIOESTERASES
  申请人：Sherman David H.

  公开号：US20090111152A1

  公开（公告）日：2009-04-30

  A method of preparing macrocycles using solid support chemistry and thioesterases is disclosed. Also disclosed are novel macrocycles.

  本发明公开了一种使用固相支持化学和硫酯酶制备大环化合物的方法。同时还公开了新型大环化合物。
• DI-SUBSTITUTED MALEIC AMIDE LINKER FOR ANTIBODY-DRUG CONJUGATING AND PREPARATION METHOD AND USE THEREOF
  申请人：Mabwell (Shanghai) Bioscience Co., Ltd.

  公开号：EP3546448A1

  公开（公告）日：2019-10-02

  Provided in the present invention are a di-substituted maleic amide linker conjugated to an antibody and a preparation method and use thereof. In particular, the present invention conjugates a strongly cytotoxic active substance to a biomacromolecule through a class of new linkers. The class of linkers can selectively act simultaneously with disulphide chains, so as to greatly improve the substance homogeneity of a conjugate. The conjugate prepared by the linker of the present invention has a high inhibitory activity on a cell strain expressing the corresponding antigen. Also provided is a method for preparing the above-mentioned conjugate and the use.

  本发明提供了一种与抗体共轭的二取代马来酰胺连接体及其制备方法和用途。特别是，本发明通过一类新型连接体将一种强细胞毒性活性物质与生物大分子连接。该类连接体可选择性地与二硫化物链同时发挥作用，从而大大提高共轭物的物质均一性。本发明的连接体制备的共轭物对表达相应抗原的细胞株具有很高的抑制活性。本发明还提供了制备上述共轭物的方法及其用途。
• Frontiers and Opportunities in Chemoenzymatic Synthesis
  作者：Jonathan D. Mortison、David H. Sherman

  DOI：10.1021/jo101124n

  日期：2010.11.5

  Natural product biosynthetic pathways have evolved enzymes with myriad activities that represent an expansive array of chemical transformations for constructing secondary metabolites. Recently, harnessing the biosynthetic potential of these enzymes through chemoenzymatic synthesis has provided a powerful tool that often rivals the most sophisticated methodologies in modern synthetic chemistry and provides new opportunities for accessing chemical diversity. Herein, we describe our research efforts with enzymes from a broad collection of biosynthetic systems, highlighting recent progress in this exciting field.