ethyl (3R,4S,5S)-4-(N-tert-butoxycarbonyl-N-methylamino)-3-methoxy-5-methyl-heptanoate | 944728-66-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (3R,4S,5S)-4-(N-tert-butoxycarbonyl-N-methylamino)-3-methoxy-5-methyl-heptanoate
• 英文别名: ethyl (3R,4S,5S)-4-((tert-butoxycarbonyl)(methyl)amino)-3-methoxy-5-methylheptanoate；ethyl (3R,4S,5S)-3-methoxy-5-methyl-4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]heptanoate
• CAS: 944728-66-9
• 化学式: C₁₇H₃₃NO₅
• 分子量: 331.453
• InChiKey: MUUBIFVIJDYOKC-GUTXKFCHSA-N

物化性质

• 沸点：
  396.8±35.0 °C(Predicted)
• 密度：
  1.001±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (3R,4S,5S)-4-(N-tert-butoxycarbonyl-N-methylamino)-3-methoxy-5-methyl-heptanoate 在 N-甲基吗啉 、 sodium hydroxide 、 氰基磷酸二乙酯 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 151.0h， 生成 (S)-2-((S)-2-(二甲基氨基)-3-甲基丁酰氨基)-N-((3R,4S,5S)-3-甲氧基-1-((s)-2-((1R,2R)-1-甲氧基-2-甲基-3-氧代-3-(((S)-2-苯基-1-(噻唑-2-基）乙基)氨基)丙基)吡咯烷-1-基)-5-甲基-1-氧代庚烷-4-基)-N,3-二甲基丁酰胺
  参考文献：
  名称：

  通过钌催化的不对称氢化全合成dolastatin 10

  摘要：

  据报道，dolastatin 10（一种有效的微管组装抑制剂）的全合成，显示出显着的抗肿瘤活性。我们的合成方法是基于钌促进的（S）-Boc-脯氨酸和（S）-Boc-异亮氨酸衍生的β-酮酯的不对称氢化反应，用于构建两个关键单元：（2 R，3 R）- Boc-dolaproine（Dap）和（3 R）-Boc-dolaisoleucine（Dil）。

  DOI：

  10.1016/j.tet.2007.03.036
• 作为产物：
  描述：

  N-[(1,1-二甲基乙氧基)羰基]-L-异亮氨酸甲酯 在 lithium aluminium tetrahydride 、 lithium hexamethyldisilazane 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 为溶剂， 反应 5.67h， 生成 ethyl (3R,4S,5S)-4-(N-tert-butoxycarbonyl-N-methylamino)-3-methoxy-5-methyl-heptanoate
  参考文献：
  名称：

  A Synthetic Dolastatin 10 Analogue Suppresses Microtubule Dynamics, Inhibits Cell Proliferation, and Induces Apoptotic Cell Death

  摘要：

  We have synthesized eight analogues (D1-D8) of dolastatin 10 containing several unique amino acid subunits. Of these agents, D5 was found to be most effective in inhibiting both He La cell proliferation and microtubule assembly in vitro. At low nanomolar concentrations, 135 inhibited the proliferation of several types of cancer cells in culture. D5 bound to tubulin with a dissociation constant of 29.4 +/- 6 mu M. D5 depolymerized microtubules in cultured cells and produced mulitpolar spindles. At its half-maximal inhibitory concentration (15 nM), DS strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. DS increased the accumulation of checkpoint proteins BubR1 and Mad2 at the kinetochoric region and caused G2/M block in these cells. The blocked cells underwent apoptosis with the activation of Jun N-terminal kinase. The results suggested that DS exerts its antiproliferative action by dampening microtubule dynamics.

  DOI：

  10.1021/jm3009629

文献信息

• OLIGOPEPTIDES AND PROCESS FOR PREPARATION THEREOF
  申请人：Council of Scientific & Industrial Research

  公开号：EP2686337B1

  公开（公告）日：2016-11-02
• CONJUGATION OF A CYTOTOXIC DRUG WITH BIS-LINKAGE
  申请人：Hangzhou DAC Biotech Co., Ltd.

  公开号：US20210369855A1

  公开（公告）日：2021-12-02

  A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease. wherein “ ” is an optional bond; X, Y, Z 1 , and Z 2 are a functional group; m 1 and n are a integer; L 1 and L 2 are a linker.
• US9200034B2
  申请人：——

  公开号：US9200034B2

  公开（公告）日：2015-12-01
• [EN] ALLENAMIDE LINKERS FOR ANTIBODY-DRUG CONJUGATE<br/>[FR] LIEURS ALLÈNAMIDE POUR CONJUGUÉ ANTICORPS-MÉDICAMENT
  申请人：[en]NANYANG TECHNOLOGICAL UNIVERSITY

  公开号：WO2023086028A2

  公开（公告）日：2023-05-19

  Disclosed herein is an antibody-drug conjugate having a structure according to formula I: Y-(A-L-(X-W)m-Z)n, wherein Y is a reduced antibody with free thiol groups, L is a linking moiety, X is an enzyme targeting moiety, W is a self-immolative linker, and Z is a drug moiety.