Dil-Dap-Doe | 159173-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: Dil-Dap-Doe
• 英文别名: (3R,4S,5S)-Dil-(2R,3R,4S)-Dap-(S)-Doe；(2R,3R)-3-methoxy-3-[(2S)-1-[(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl]pyrrolidin-2-yl]-2-methyl-N-[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]propanamide
• CAS: 159173-45-2
• 化学式: C₃₀H₄₆N₄O₄S
• 分子量: 558.786
• InChiKey: LFWMTQLEWYFDLJ-GSHADLMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Dil-Dap-Doe 在 N-甲基吗啉 、 bromo-tris-dimethylamino-phosphonium hexafluorophosphate 、 氰基磷酸二乙酯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.17h， 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：

  立体合成dolastatin 10及其同类物

  摘要：

  有效合成dolastatin 10（1），一种来自海兔Dolabella auricularia的有效抗肿瘤肽，以立体选择性方式实现。Trisnordolastatin 10（2）及其C 9-受体（3）也已合成。

  DOI：

  10.1016/s0040-4020(01)80547-0
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醇 在 吡啶 、 盐酸 、 manganese(IV) oxide 、 三氧化硫 、 氢溴酸 、 溶剂黄146 、 三乙胺 、 焦碳酸二乙酯 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 苯 为溶剂， 反应 21.33h， 生成 Dil-Dap-Doe
  参考文献：
  名称：

  An expeditious synthesis of dolastatin 10

  摘要：

  Total synthesis of dolastatin 10 (1) was completed by developing an efficient synthesis of two key amino acid components, Dil (6) and Dap (11), and subsequent stepwise coupling of five amino acid components from C-terminal Doe.

  DOI：

  10.1016/s0040-4039(00)79932-1

文献信息

• Total synthesis of dolastatin 10 through ruthenium-catalyzed asymmetric hydrogenations
  作者：Céline Mordant、Sébastien Reymond、Hitoshi Tone、Damien Lavergne、Ridha Touati、Bechir Ben Hassine、Virginie Ratovelomanana-Vidal、Jean-Pierre Genet

  DOI：10.1016/j.tet.2007.03.036

  日期：2007.7

  synthesis of dolastatin 10, a potent inhibitor of microtubule assembly, which displayed remarkable antineoplastic activity, is reported. Our synthetic approach was based upon ruthenium-promoted asymmetric hydrogenation of β-keto esters derived from (S)-Boc-proline and (S)-Boc-isoleucine for the construction of the two key units: (2R,3R)-Boc-dolaproine (Dap) and (3R)-Boc-dolaisoleucine (Dil).

  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）。
• [EN] ANTI-CANCER COMPOUNDS AND CONJUGATES THEREOF<br/>[FR] COMPOSÉS ANTICANCÉREUX ET CONJUGUÉS DE CEUX-CI
  申请人：SIRENAS LLC

  公开号：WO2017058808A1

  公开（公告）日：2017-04-06

  Disclosed are compounds based on dolastatins, drug-conjugates, methods of preparing drug-conjugates, and uses thereof. Also disclosed are pharaceutical compositions and methods of treatment. The compounds and drug-conjugates disclosed herein can be used to treat diseases such as bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, glioblastoma, pancreatic cancer, prostate cancer, and thyroid cancer.

  本发明涉及基于多拉斯塔丁的化合物、药物结合物、制备药物结合物的方法以及其用途。还公开了药物组合物和治疗方法。本文所述的化合物和药物结合物可用于治疗膀胱癌、乳腺癌、结肠癌、直肠癌、子宫内膜癌、肾癌、肺癌、黑色素瘤、非何杰金淋巴瘤、胶质母细胞瘤、胰腺癌、前列腺癌和甲状腺癌等疾病。
• Anti-cancer compounds and conjugates thereof
  申请人：SIRENAS LLC

  公开号：US10722593B2

  公开（公告）日：2020-07-28

  Disclosed are compounds based on dolastatins, drug-conjugates, methods of preparing drug-conjugates, and uses thereof. Also disclosed are pharmaceutical compositions and methods of treatment. The compounds and drug-conjugates disclosed herein can be used to treat diseases such as bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, glioblastoma, pancreatic cancer, prostate cancer, and thyroid cancer.

  所公开的是基于多拉斯汀类的化合物、药物结合物、药物结合物的制备方法及其用途。还公开了药物组合物和治疗方法。本文公开的化合物和药物轭合物可用于治疗膀胱癌、乳腺癌、结肠癌、直肠癌、子宫内膜癌、肾癌、肺癌、黑色素瘤、非霍奇金淋巴瘤、胶质母细胞瘤、胰腺癌、前列腺癌和甲状腺癌等疾病。
• Synthése de la dolastatine 10 et de la [R-doe]-dolastatine 10
  作者：Florence Roux、Isabelle Maugras、Joël Poncet、Gilles Niel、Patrick Jouin

  DOI：10.1016/s0040-4020(01)80692-x

  日期：1994.5

  A stepwise synthesis of dolastatin 10 starting from the dolaphenine residue is described. The chiral dola isoleuine and dolaproine residues were obtained by 5-step procedures from the corresponding N-Boc amino acid. The key steps are respectively the NaBH4 reduction of an allylic ketone and the addition of an achiral Z-crotylboronate on the N-Boc-L-prolinal. Peptidic couplings were efficiently realised with reagents developed in the laboratory.
• ANTI-CANCER COMPOUNDS AND CONJUGATES THEREOF
  申请人：SIRENAS LLC

  公开号：US20200316214A1

  公开（公告）日：2020-10-08

  Disclosed herein are compounds, drug-conjugates thereof, methods of preparing drug-conjugates, and uses thereof. Also disclosed are pharmaceutical compositions and methods of treatment. The compounds and drug-conjugates disclosed herein can be used to treat a variety of conditions, diseases and ailments such as bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, glioblastoma, pancreatic cancer, prostate cancer, and thyroid cancer.