1,2-(10,11-docosandiyne-1,22-dioyl)-3-O-benzylglycerol | 217821-19-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 1,2-(10,11-docosandiyne-1,22-dioyl)-3-O-benzylglycerol
• 英文别名: 2-(Phenylmethoxymethyl)-1,4-dioxacyclohexacosa-14,16-diyne-5,26-dione
• CAS: 217821-19-7
• 化学式: C₃₂H₄₄O₅
• 分子量: 508.698
• InChiKey: PIEOUFAPTHFEHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2-(10,11-docosandiyne-1,22-dioyl)-3-O-benzylglycerol 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 以60%的产率得到1,2-(docosane-1,22-dioyl)glycerol
  参考文献：
  名称：

  Synthesis of Macrocyclic Diacyl/Dialkyl Glycerols Containing Disulfide Tether and Studies of Their Effects upon Incorporation in DPPC Membranes. Implications in the Design of Phospholipase A₂ Modulators

  摘要：

  A general method for the preparation of novel disulfide-tethered macrocyclic diacylglycerols (DAGs) has been described. Overall synthesis involved stepwise protection, acylation, and deprotection to yield the bis(omega-bromoacyl) glycerols. In the crucial macrocyclization step, a unique reagent, benzyltriethylammonium tetrathiomolybdate (BTAT), has been used to convert individual bis(omega-bromoacyl) glycerols to their respective macrocyclic disulfides. DAG 6, which had ether linkages between hydrocarbon chains and the glycerol backbone, was also synthesized from an appropriate precursor using a similar protocol. One of the DAGs (DAG 5) had a carbon-carbon tether instead of a disulfide one and was synthesized using modified Glaser coupling. Preparation of alpha-disulfide-tethered DAG (DAG 4) required an alternative method, as treatment of the bisbromo precursor with BTAT gave a mixture of several compounds from which separation of the target molecule was cumbersome. To avoid this problem, the bisbromide was converted to its corresponding dithiocyanate, which on further treatment with BTAT yielded the desired DAG (DAG 4) in good yield. Upon treatment with the reducing agent dithiothreitol (DTT), the DAGs that contain a disulfide tether could be quantitatively converted to their "open-chain" thiol analogues. These macrocyclic DAGs and their reduced "open-chain" analogues have been incorporated in DPPC vesicles to study their effect on model membranes. Upon incorporation of DAG 1 in DPPC vesicles, formation of new isotropic phases was observed by P-31 NMR, These isotropic phases disappeared completely on opening the macrocyclic ring by a reducing agent. The thermotropic properties of DPPC bilayers having DAGs (1-6) incorporated at various concentrations were studied by differential scanning calorimetry. Incorporation of DAGs in general reduced the cooperativity unit (CU) of the vesicles. Similar experiments with reduced "open-chain" DAGs incorporated in a DPPC bilayer indicated a recovery of CU with respect to their macrocyclic "disulfide" counterparts. The effect of inclusion of these DAGs on the activity of phospholipase A(2) (PLA(2)) was studied in vitro. Incorporation of DAC 1 in DPPC membranes potentiated both bee venom and cobra venom PLA(2) activities.

  DOI：

  10.1021/jo980866b
• 作为产物：
  描述：

  1-苄基-2,3-异亚丙基-rac-甘油 在 4-二甲氨基吡啶 、 四甲基乙二胺 、 氧气 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 、 copper(l) chloride 作用下， 以 甲醇 、 四氯化碳 、 水 、 xylene 为溶剂， 反应 12.0h， 生成 1,2-(10,11-docosandiyne-1,22-dioyl)-3-O-benzylglycerol
  参考文献：
  名称：

  Synthesis of Macrocyclic Diacyl/Dialkyl Glycerols Containing Disulfide Tether and Studies of Their Effects upon Incorporation in DPPC Membranes. Implications in the Design of Phospholipase A₂ Modulators

  摘要：

  A general method for the preparation of novel disulfide-tethered macrocyclic diacylglycerols (DAGs) has been described. Overall synthesis involved stepwise protection, acylation, and deprotection to yield the bis(omega-bromoacyl) glycerols. In the crucial macrocyclization step, a unique reagent, benzyltriethylammonium tetrathiomolybdate (BTAT), has been used to convert individual bis(omega-bromoacyl) glycerols to their respective macrocyclic disulfides. DAG 6, which had ether linkages between hydrocarbon chains and the glycerol backbone, was also synthesized from an appropriate precursor using a similar protocol. One of the DAGs (DAG 5) had a carbon-carbon tether instead of a disulfide one and was synthesized using modified Glaser coupling. Preparation of alpha-disulfide-tethered DAG (DAG 4) required an alternative method, as treatment of the bisbromo precursor with BTAT gave a mixture of several compounds from which separation of the target molecule was cumbersome. To avoid this problem, the bisbromide was converted to its corresponding dithiocyanate, which on further treatment with BTAT yielded the desired DAG (DAG 4) in good yield. Upon treatment with the reducing agent dithiothreitol (DTT), the DAGs that contain a disulfide tether could be quantitatively converted to their "open-chain" thiol analogues. These macrocyclic DAGs and their reduced "open-chain" analogues have been incorporated in DPPC vesicles to study their effect on model membranes. Upon incorporation of DAG 1 in DPPC vesicles, formation of new isotropic phases was observed by P-31 NMR, These isotropic phases disappeared completely on opening the macrocyclic ring by a reducing agent. The thermotropic properties of DPPC bilayers having DAGs (1-6) incorporated at various concentrations were studied by differential scanning calorimetry. Incorporation of DAGs in general reduced the cooperativity unit (CU) of the vesicles. Similar experiments with reduced "open-chain" DAGs incorporated in a DPPC bilayer indicated a recovery of CU with respect to their macrocyclic "disulfide" counterparts. The effect of inclusion of these DAGs on the activity of phospholipase A(2) (PLA(2)) was studied in vitro. Incorporation of DAC 1 in DPPC membranes potentiated both bee venom and cobra venom PLA(2) activities.

  DOI：

  10.1021/jo980866b

文献信息

• Continuous flow macrocyclization at high concentrations: synthesis of macrocyclic lipids
  作者：Anne-Catherine Bédard、Sophie Régnier、Shawn K. Collins

  DOI：10.1039/c3gc40872h

  日期：——

  A phase separation/continuous flow macrocyclization protocol eliminates the need for high-dilution conditions and can be used to prepare gram quantities of biologically relevant macrocyclic lipid structures. The method presents several green advantages towards macrocycle synthesis: (1) the prevention of unwanted oligomers and waste, (2) a reduction in the large quantities of toxic, volatile organic solvents and (3) the use of PEG as an environmentally benign reaction media. Macrocycles could be synthesized in high yields (up to 99%) in short reaction times (1.5 h) and on gram scales without the need to alter the reaction conditions.

  相分离/连续流大环化方案无需高稀释条件，可用于制备克级数量的生物相关大环脂质结构。该方法在大环合成方面具有多项绿色优势：(1) 避免了不必要的低聚物和废物；(2) 减少了大量有毒、易挥发的有机溶剂；(3) 使用 PEG 作为对环境无害的反应介质。大环化合物的合成收率高（高达 99%），反应时间短（1.5 小时），以克为单位，无需改变反应条件。
• Synthesis of Macrocyclic Diacyl/Dialkyl Glycerols Containing Disulfide Tether and Studies of Their Effects upon Incorporation in DPPC Membranes. Implications in the Design of Phospholipase A₂ Modulators
  作者：Santanu Bhattacharya、Sangita Ghosh、Kalpathy R. K. Easwaran

  DOI：10.1021/jo980866b

  日期：1998.12.1

  A general method for the preparation of novel disulfide-tethered macrocyclic diacylglycerols (DAGs) has been described. Overall synthesis involved stepwise protection, acylation, and deprotection to yield the bis(omega-bromoacyl) glycerols. In the crucial macrocyclization step, a unique reagent, benzyltriethylammonium tetrathiomolybdate (BTAT), has been used to convert individual bis(omega-bromoacyl) glycerols to their respective macrocyclic disulfides. DAG 6, which had ether linkages between hydrocarbon chains and the glycerol backbone, was also synthesized from an appropriate precursor using a similar protocol. One of the DAGs (DAG 5) had a carbon-carbon tether instead of a disulfide one and was synthesized using modified Glaser coupling. Preparation of alpha-disulfide-tethered DAG (DAG 4) required an alternative method, as treatment of the bisbromo precursor with BTAT gave a mixture of several compounds from which separation of the target molecule was cumbersome. To avoid this problem, the bisbromide was converted to its corresponding dithiocyanate, which on further treatment with BTAT yielded the desired DAG (DAG 4) in good yield. Upon treatment with the reducing agent dithiothreitol (DTT), the DAGs that contain a disulfide tether could be quantitatively converted to their "open-chain" thiol analogues. These macrocyclic DAGs and their reduced "open-chain" analogues have been incorporated in DPPC vesicles to study their effect on model membranes. Upon incorporation of DAG 1 in DPPC vesicles, formation of new isotropic phases was observed by P-31 NMR, These isotropic phases disappeared completely on opening the macrocyclic ring by a reducing agent. The thermotropic properties of DPPC bilayers having DAGs (1-6) incorporated at various concentrations were studied by differential scanning calorimetry. Incorporation of DAGs in general reduced the cooperativity unit (CU) of the vesicles. Similar experiments with reduced "open-chain" DAGs incorporated in a DPPC bilayer indicated a recovery of CU with respect to their macrocyclic "disulfide" counterparts. The effect of inclusion of these DAGs on the activity of phospholipase A(2) (PLA(2)) was studied in vitro. Incorporation of DAC 1 in DPPC membranes potentiated both bee venom and cobra venom PLA(2) activities.