(E)-5-((4-methoxybenzyl)oxy)-2-methylpent-2-en-1-ol | 208581-45-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-5-((4-methoxybenzyl)oxy)-2-methylpent-2-en-1-ol
• 英文别名: (E)-5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenol；(E)-5-[(4-methoxyphenyl)methoxy]-2-methylpent-2-en-1-ol
• CAS: 208581-45-7
• 化学式: C₁₄H₂₀O₃
• 分子量: 236.311
• InChiKey: POCCBCQRIQZACA-UUILKARUSA-N

物化性质

• 沸点：
  363.2±42.0 °C(Predicted)
• 密度：
  1.045±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-5-((4-methoxybenzyl)oxy)-2-methylpent-2-en-1-ol 在 2,6-二甲基吡啶 、 titanium(IV) isopropylate 、 4-二甲氨基吡啶 、 aluminum (III) chloride 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 三甲基氯硅烷 、 甲酸 、 L-(+)-酒石酸二乙酯 、 三丁基膦 、 四丁基氟化铵 、 sodium hexamethyldisilazane 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 乙腈 为溶剂， 反应 101.75h， 生成 cryptophycin 52
  参考文献：
  名称：

  Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies

  摘要：

  Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50 values at low nanomolar levels (0.58-1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI-N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112364
• 作为产物：
  描述：

  3-[(4-甲氧基苄基)氧基]-1-丙醇 在 草酰氯 、 sodium hydride 、 二异丁基氢化铝 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 13.5h， 生成 (E)-5-((4-methoxybenzyl)oxy)-2-methylpent-2-en-1-ol
  参考文献：
  名称：

  脱氢-脱磷-去铁霉素的合成和去甲鸟氨酸的正式全合成。

  摘要：

  已经成功合成了合成的邻苯二酚（1）及其相关的同类物二氢-去磷酸-磷霉素2。该路线依赖于使用Sharpless二羟基化将绝对立体化学设定在C -8/9和Noyori转移氢化和Leighton烯丙基化分别设定C -11和C -5相对立体化学。最后，一个的发散官能Ç -12/13炔被用来建立Z，E脱氢脱磷酸fostriecin的-dienyne 2和Z，Z，E fostriecin（的三烯1）。

  DOI：

  10.1021/acs.orglett.9b03120

文献信息

• Formal Total Synthesis of Fostriecin by 1,4-Asymmetric Induction with an Alkyne-Cobalt Complex
  作者：Yujiro Hayashi、Hirofumi Yamaguchi、Maya Toyoshima、Kotaro Okado、Takumi Toyo、Mitsuru Shoji

  DOI：10.1002/chem.201000795

  日期：2010.9.3

  4‐relationship is considered difficult, we have developed a notable 1,4‐asymmetric induction that utilizes an alkyne–cobalt complex for the control of C5 stereochemistry by the C8 stereogenic center. The stereochemistry at C11 was established by 1,3‐asymmetric induction with a higher‐order alkynyl‐zinc reagent. Thus, only one asymmetric reaction requiring an external chiral auxiliary was employed in this

  已经完成了受保护的去磷酸钙丝素的合成，从而正式合成了泊丝汀。合成方面的挑战是建立四个立体基因中心和构象不稳定的顺式-顺式-反式-三烯部分。先前的总合成已经使用了至少两个不对称反应，这需要使用外部手性助剂。尽管认为在1,4关系中进行远程立体诱导很困难，但我们开发了一种显着的1,4-不对称诱导，利用炔-钴复合物通过C8立体异构中心控制C5立体化学。C11的立体化学是通过用较高级的炔基锌试剂进行的1,3-不对称诱导建立的。因此，在该途径中仅使用了一个需要外部手性助剂的不对称反应。不稳定的顺式-顺式-反式三烯单元是在合成的后期通过二烯炔和醛单元的非对映选择性偶联而构建的，然后还原。
• Formal Total Synthesis of Fostriecin via 1,4-Asymmetric Induction Using Cobalt-Alkyne Complex
  作者：Yujiro Hayashi、Hirofumi Yamaguchi、Maya Toyoshima、Kotaro Okado、Takumi Toyo、Mitsuru Shoji

  DOI：10.1021/ol800195g

  日期：2008.4.1

  accomplished. Two of the four chiral centers are controlled by an external chiral auxiliary and the other two are synthesized stereoselectively, one by a novel 1,4-asymmetric induction using cobalt-alkyne complex, and the other by 1,3-asymmetric induction.

  已经完成了受保护的去磷酸钙丝素的合成，从而正式合成了泊丝汀。四个手性中心中的两个由外部手性助剂控制，另两个通过立体选择性合成，一个通过使用钴-炔配合物的新型1,4-不对称诱导，另一个通过1,3-不对称诱导。
• A short enantioselective synthesis of a component of cryptophycin A and arenastatin A
  作者：Masaaki Furuyama、Isao Shimizu

  DOI：10.1016/s0957-4166(98)00119-0

  日期：1998.4

  Synthesis of 1, a component of cryptophycin A 2 and arenastatin A 3, was achieved by applying palladium-catalyzed reductive ring opening of optically active alkenyl oxirane 13 for the construction of the vicinal stereogenic centers. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Synthesis of chiral 4-hydroxy-2,3-unsaturated carbonyl compounds from 3,4-epoxy alcohols by oxidation: application in the formal synthesis of macrosphelide A
  作者：Tushar K Chakraborty、Subhas Purkait、Sanjib Das

  DOI：10.1016/j.tet.2003.09.070

  日期：2003.11

  An interesting transformation during the oxidation of 3,4-epoxy alcohols 1a-d, derived from the corresponding homoallylic alcohols, led to the formation of 4-hydroxy-2,3-unsaturated carbonyls 2a-d in very good yields. One of these products 2c was transformed into the functionalised carboxylic acid 5, an advanced stage intermediate from which the total synthesis of macrosphelide A has been reported. (C) 2003 Elsevier Ltd. All rights reserved.
• Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies
  作者：Qinhuai Lai、Mengdan Wu、Ruixue Wang、Weirong Lai、Yiran Tao、Ying Lu、Yuxi Wang、Lin Yu、Ruirui Zhang、Yujia Peng、Xiaohua Jiang、Yuyin Fu、Xin Wang、Zhixiong Zhang、Cuiyu Guo、Wei Liao、Yiwen Zhang、Tairan Kang、Hao Chen、Yuqin Yao、Lantu Gou、Jinliang Yang

  DOI：10.1016/j.ejmech.2020.112364

  日期：2020.8

  Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50 values at low nanomolar levels (0.58-1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI-N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.