2,6,10,15,19,23‐hexamethyl‐1,6,10,14,18,22‐tetracosahexaen‐3‐ol

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2,6,10,15,19,23‐hexamethyl‐1,6,10,14,18,22‐tetracosahexaen‐3‐ol
• 英文别名: 2,6,10,15,19,23-hexamethyltetracosa-1,6,10,14,18,22-hexaen-3-ol
• 化学式: C₃₀H₅₀O
• 分子量: 426.726
• InChiKey: JLUBMMAQMKVTGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  31
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2,6,10,15,19,23‐hexamethyl‐1,6,10,14,18,22‐tetracosahexaen‐3‐ol 在 1-羟基苯并三唑 、 丙酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.0h， 生成 N-{9-2,3-bis[(tert-butyldimethylsilyl)oxy-5-[(tertbutyldimethylsilyl)oxy]methyloxolan-2-yl]-9H-purin-6-yl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide
  参考文献：
  名称：

  Translation of nanomedicines from lab to industrial scale synthesis: The case of squalene-adenosine nanoparticles

  摘要：

  A large variety of nanoparticle-based delivery systems have become increasingly important for diagnostic and/or therapeutic applications. Yet, the numerous physical and chemical parameters that influence both the biological and colloidal properties of nanoparticles remain poorly understood. This complicates the ability to reliably produce and deliver well-defined nanocarriers which often leads to inconsistencies, conflicts in the published literature and, ultimately, poor translation to the clinics. A critical issue lies in the challenge of scaling-up nanomaterial synthesis and formulation from the lab to industrial scale while maintaining control over their diverse properties. Studying these phenomena early on in the development of a therapeutic agent often requires partnerships between the public and private sectors which are hard to establish.In this study, through the particular case of squalene-adenosine nanoparticles, we reported on the challenges encountered in the process of scaling-up nanomedicines synthesis. Here, squalene (the carrier) was functionalized and conjugated to adenosine (the active drug moiety) at an industrial scale in order to obtain large quantities of biocompatible and biodegradable nanoparticles. After assessing nanoparticle batch-to-batch consistency, we demonstrated that the presence of squalene analogs resulting from industrial scale-up may influence several features such as size, surface charge, protein adsorption, cytotoxicity and crystal structure. These analogs were isolated, characterized by multiple stage mass spectrometry, and their influence on nanoparticle properties further evaluated. We showed that slight variations in the chemical profile of the nanocarrier's constitutive material can have a tremendous impact on the reproducibility of nanoparticle properties. In a context where several generics of approved nanoformulated drugs are set to enter the market in the coming years, characterizing and solving these issues is an important step in the pharmaceutical development of nanomedicines.

  DOI：

  10.1016/j.jconrel.2019.06.040
• 作为产物：
  描述：

  squalene 在 N-溴代丁二酰亚胺(NBS) 、 aluminum isopropoxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 19.5h， 生成 2,6,10,15,19,23‐hexamethyl‐1,6,10,14,18,22‐tetracosahexaen‐3‐ol
  参考文献：
  名称：

  Translation of nanomedicines from lab to industrial scale synthesis: The case of squalene-adenosine nanoparticles

  摘要：

  A large variety of nanoparticle-based delivery systems have become increasingly important for diagnostic and/or therapeutic applications. Yet, the numerous physical and chemical parameters that influence both the biological and colloidal properties of nanoparticles remain poorly understood. This complicates the ability to reliably produce and deliver well-defined nanocarriers which often leads to inconsistencies, conflicts in the published literature and, ultimately, poor translation to the clinics. A critical issue lies in the challenge of scaling-up nanomaterial synthesis and formulation from the lab to industrial scale while maintaining control over their diverse properties. Studying these phenomena early on in the development of a therapeutic agent often requires partnerships between the public and private sectors which are hard to establish.In this study, through the particular case of squalene-adenosine nanoparticles, we reported on the challenges encountered in the process of scaling-up nanomedicines synthesis. Here, squalene (the carrier) was functionalized and conjugated to adenosine (the active drug moiety) at an industrial scale in order to obtain large quantities of biocompatible and biodegradable nanoparticles. After assessing nanoparticle batch-to-batch consistency, we demonstrated that the presence of squalene analogs resulting from industrial scale-up may influence several features such as size, surface charge, protein adsorption, cytotoxicity and crystal structure. These analogs were isolated, characterized by multiple stage mass spectrometry, and their influence on nanoparticle properties further evaluated. We showed that slight variations in the chemical profile of the nanocarrier's constitutive material can have a tremendous impact on the reproducibility of nanoparticle properties. In a context where several generics of approved nanoformulated drugs are set to enter the market in the coming years, characterizing and solving these issues is an important step in the pharmaceutical development of nanomedicines.

  DOI：

  10.1016/j.jconrel.2019.06.040

文献信息

• Translation of nanomedicines from lab to industrial scale synthesis: The case of squalene-adenosine nanoparticles
  作者：Flavio Dormont、Marie Rouquette、Clement Mahatsekake、Frédéric Gobeaux、Arnaud Peramo、Romain Brusini、Serge Calet、Fabienne Testard、Sinda Lepetre-Mouelhi、Didier Desmaële、Mariana Varna、Patrick Couvreur

  DOI：10.1016/j.jconrel.2019.06.040

  日期：2019.8

  A large variety of nanoparticle-based delivery systems have become increasingly important for diagnostic and/or therapeutic applications. Yet, the numerous physical and chemical parameters that influence both the biological and colloidal properties of nanoparticles remain poorly understood. This complicates the ability to reliably produce and deliver well-defined nanocarriers which often leads to inconsistencies, conflicts in the published literature and, ultimately, poor translation to the clinics. A critical issue lies in the challenge of scaling-up nanomaterial synthesis and formulation from the lab to industrial scale while maintaining control over their diverse properties. Studying these phenomena early on in the development of a therapeutic agent often requires partnerships between the public and private sectors which are hard to establish.In this study, through the particular case of squalene-adenosine nanoparticles, we reported on the challenges encountered in the process of scaling-up nanomedicines synthesis. Here, squalene (the carrier) was functionalized and conjugated to adenosine (the active drug moiety) at an industrial scale in order to obtain large quantities of biocompatible and biodegradable nanoparticles. After assessing nanoparticle batch-to-batch consistency, we demonstrated that the presence of squalene analogs resulting from industrial scale-up may influence several features such as size, surface charge, protein adsorption, cytotoxicity and crystal structure. These analogs were isolated, characterized by multiple stage mass spectrometry, and their influence on nanoparticle properties further evaluated. We showed that slight variations in the chemical profile of the nanocarrier's constitutive material can have a tremendous impact on the reproducibility of nanoparticle properties. In a context where several generics of approved nanoformulated drugs are set to enter the market in the coming years, characterizing and solving these issues is an important step in the pharmaceutical development of nanomedicines.