16-fluoropalmitoyl chloride | 299177-76-7

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 酰卤
• 英文名称: 16-fluoropalmitoyl chloride
• 英文别名: 16-fluorohexadecanoyl chloride；16-fluorohexadecanoyl Chloride
• CAS: 299177-76-7
• 化学式: C₁₆H₃₀ClFO
• 分子量: 292.865
• InChiKey: AXSMGXGRKPGDSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  19
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  16-fluoropalmitoyl chloride 在 吡啶 、 三乙胺 作用下， 以 氯仿 、 苯 为溶剂， 反应 49.0h， 生成 3-O-benzyl-1-(16-fluoropalmitoyl)-2-palmitoylglycerol
  参考文献：
  名称：

  [F-18]labeling of 1,2-diacylglycerols

  摘要：

  We have developed two kinds of [F-18]labeled 1,2-diacylglycerols (1,2-DAGs) such as 1-(omega-[F-18]fluoroacyl)-2-acylglycerols (1*,2-[F-18]FDAGs) and 2-(omega-[F-18]fluoroacyl)-1-acylglycerols (1,2*-[F-18]FDAGs) for imaging receptor-mediated phosphatidyl-inositol (PI) turnover responses by positron emission tomography (PET). The 1*,2-[F-18]FDAGs were synthesized by the reaction of 2-monoacyl glycerols with omega-[F-18]fluoroacyl chlorides (method A) and 1-(16-[F-18]fluoro palmitoyl)-2-palmitoylglycerol (1*,2-[F-18]FDAG(C16,C16)) and 1-(8-[F-18]fluoro octanoyl)-2-palmitoylglycerol (1*,2-[F-18]FDAG(C8,C16)) were synthesized using method A. However, during the synthesis of 1,2*-[F-18]FDAGs, we adopted the hydrogenolysis to remove a benzyl group from 3-O-benzyl-2-(omega-[F-18]fluoroacyl)-1-acylglycerol, which was synthesized by the nucleophilic exchange reaction of 3-O-benzyl-2-(omega-bromoacyl)-1-acylglycerol with [F-18]F- (method B) and 2-(16-[F-18]fluoropalmitoyl)-1-palmitoylglycerol (1,2*-[F-18]FDAG(C16,C16)) and [F-18]fluorooctanoyl)-1-palmitoylglycerol (1,2*-[F-18]FDAG(C16,C8)) were produced using method B. The purified 1*,2-[F-18]FDAGs were obtained in radiochemical yields of 8-35 % (based on [F-18]F-) with radiochemical purities of > 97 % and the purified 1,2*-[F-18]FDAGs were in radiochemical yields of 5-15 % with radiochemical purities of > 95 %. The total synthesis time from the start of the reactive [F-18]F- production, including HPLC purification, was 100 - 135 min (method A) and 115 - 175 min (method B), respectively. It has already been used for more than 100 preparations of 1*,2-[F-18]FDAG(C16,C16), 1*,2-[F-18]FDAG(C8, C16), and 1,2*-[F-18]FDAG(C16,C16), 1,2*-[F-18]FDAG(C16,C8) for animal studies.

  DOI：

  10.1002/1099-1344(200008)43:9<943::aid-jlcr379>3.0.co;2-v
• 作为产物：
  描述：

  16-氟十六烷酸 在 氯化亚砜 作用下， 反应 1.0h， 生成 16-fluoropalmitoyl chloride
  参考文献：
  名称：

  [F-18]labeling of 1,2-diacylglycerols

  摘要：

  We have developed two kinds of [F-18]labeled 1,2-diacylglycerols (1,2-DAGs) such as 1-(omega-[F-18]fluoroacyl)-2-acylglycerols (1*,2-[F-18]FDAGs) and 2-(omega-[F-18]fluoroacyl)-1-acylglycerols (1,2*-[F-18]FDAGs) for imaging receptor-mediated phosphatidyl-inositol (PI) turnover responses by positron emission tomography (PET). The 1*,2-[F-18]FDAGs were synthesized by the reaction of 2-monoacyl glycerols with omega-[F-18]fluoroacyl chlorides (method A) and 1-(16-[F-18]fluoro palmitoyl)-2-palmitoylglycerol (1*,2-[F-18]FDAG(C16,C16)) and 1-(8-[F-18]fluoro octanoyl)-2-palmitoylglycerol (1*,2-[F-18]FDAG(C8,C16)) were synthesized using method A. However, during the synthesis of 1,2*-[F-18]FDAGs, we adopted the hydrogenolysis to remove a benzyl group from 3-O-benzyl-2-(omega-[F-18]fluoroacyl)-1-acylglycerol, which was synthesized by the nucleophilic exchange reaction of 3-O-benzyl-2-(omega-bromoacyl)-1-acylglycerol with [F-18]F- (method B) and 2-(16-[F-18]fluoropalmitoyl)-1-palmitoylglycerol (1,2*-[F-18]FDAG(C16,C16)) and [F-18]fluorooctanoyl)-1-palmitoylglycerol (1,2*-[F-18]FDAG(C16,C8)) were produced using method B. The purified 1*,2-[F-18]FDAGs were obtained in radiochemical yields of 8-35 % (based on [F-18]F-) with radiochemical purities of > 97 % and the purified 1,2*-[F-18]FDAGs were in radiochemical yields of 5-15 % with radiochemical purities of > 95 %. The total synthesis time from the start of the reactive [F-18]F- production, including HPLC purification, was 100 - 135 min (method A) and 115 - 175 min (method B), respectively. It has already been used for more than 100 preparations of 1*,2-[F-18]FDAG(C16,C16), 1*,2-[F-18]FDAG(C8, C16), and 1,2*-[F-18]FDAG(C16,C16), 1,2*-[F-18]FDAG(C16,C8) for animal studies.

  DOI：

  10.1002/1099-1344(200008)43:9<943::aid-jlcr379>3.0.co;2-v

文献信息

• A Novel Substrate Radiotracer for Molecular Imaging of SIRT2 Expression and Activity with Positron Emission Tomography
  作者：Robin E. Bonomi、Maxwell Laws、Vadim Popov、Swatabdi Kamal、Shreya Potukutchi、Aleksandr Shavrin、Xin Lu、Nashaat Turkman、Ren-Shyan Liu、Thomas Mangner、Juri G. Gelovani

  DOI：10.1007/s11307-017-1149-8

  日期：2018.8

  The purpose of this study was to develop a SIRT2-specific substrate-type radiotracer for non-invasive PET imaging of epigenetic regulatory processes mediated by SIRT2 in normal and disease tissues. A library of compounds containing tert-butyloxycarbonyl-lysine-aminomethylcoumarin backbone was derivatized with fluoroalkyl chains 3–16 carbons in length. SIRT2 most efficiently cleaved the myristoyl, followed by 12-fluorododecanoic and 10-fluorodecanoic groups (Kcat/Km 716.5 ± 72.8, 615.4 ± 50.5, 269.5 ± 52.1/s mol, respectively). Radiosynthesis of 12- [18F]fluorododecanoic aminohexanoicanilide (12-[18F]DDAHA) was achieved by nucleophilic radiofluorination of 12-iododecanoic-AHA precursor. A significantly higher accumulation of 12-[18F]DDAHA was observed in MCF-7 and MDA-MB-435 cells in vitro as compared to U87, MiaPaCa, and MCF10A, which was consistent with levels of SIRT2 expression. Initial in vivo studies using 12-[18F]DDAHA conducted in a 9L glioma-bearing rats were discouraging, due to rapid defluorination of this radiotracer upon intravenous administration, as evidenced by significant accumulation of F-18 radioactivity in the skull and other bones, which confounded the interpretation of images of radiotracer accumulation within the tumor and other regions of the brain. The next generation of SIRT2-specific radiotracers resistant to systemic defluorination should be developed using alternative sites of radiofluorination on the aliphatic chain of DDAHA. A SIRT2-selective radiotracer may provide information about SIRT2 expression and activity in tumors and normal organs and tissues, which may help to better understand the roles of SIRT2 in different diseases.

  本研究的目的是开发一种特异性针对SIRT2的底物型放射性示踪剂，以便对正常和病变组织中由SIRT2介导的表观遗传调控过程进行非侵入性PET成像。我们制备了一系列包含叔丁氧羰基-赖氨酸-氨甲基香豆素主链的化合物，并用长度为3至16个碳的氟烷基链进行衍生化。SIRT2最有效地切割肉豆蔻酰基，其次是12-氟十二酸和10-氟十酸基团（Kcat/Km 716.5 ± 72.8、615.4 ± 50.5、269.5 ± 52.1/s mol，分别）。通过对12-碘十二酸-AHA前体进行亲核放射性氟化，成功合成了12-[18F]氟十二酸氨己酰胺（12-[18F]DDAHA）。在体外研究中，MCF-7和MDA-MB-435细胞中观察到12-[18F]DDAHA的显著更高积累，与U87、MiaPaCa和MCF10A细胞相比，这与SIRT2的表达水平一致。对9L胶质瘤-bearing大鼠进行的初步体内研究结果令人沮丧，因为该放射性示踪剂在静脉给药后迅速去氟化，导致F-18放射活性在颅骨和其他骨骼中的显著积累，从而使得肿瘤及脑部其他区域示踪剂积累图像的解读变得困难。下一代抵抗系统性去氟化的SIRT2特异性放射性示踪剂应使用DDAHA脂肪链上的其他氟化位点进行开发。SIRT2选择性放射性示踪剂可能提供肿瘤和正常器官及组织中SIRT2表达和活性的信息，帮助更好地理解SIRT2在不同疾病中的作用。
• [EN] NOVEL DERIVATIVES OF PALIPERIDONE AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS DE PALIPÉRIDONE ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：ZENVISION PHARMA LLP

  公开号：WO2019162746A1

  公开（公告）日：2019-08-29

  The present disclosure relates to novel hydroxyl or halogen substituted derivatives of C11- C22 alkanoic acid ester of Paliperidone compound of formula (formula II) and process for preparing the same. The said compounds used in pharmaceutical composition for the treatment of schizophrenia and schizoaffective disorder, wherein, R= C10-C21 alkyl substituted by hydroxy or halogen.

  本公开涉及Paliperidone化合物的C11-C22烷基羟基或卤素取代衍生物（式II的化合物）的新型衍生物，以及制备这些衍生物的方法。所述化合物用于治疗精神分裂症和分裂情感障碍的药物组合物中，其中R=C10-C21烷基，其被羟基或卤素取代。
• Derivatives of paliperidone and process for the preparation thereof
  申请人：Zenvision Pharma LLP

  公开号：US11377445B2

  公开（公告）日：2022-07-05

  The present disclosure relates to novel hydroxyl or halogen substituted derivatives of C11-C22 alkanoic acid ester of Paliperidone compound of formula (formula II) and process for preparing the same. The said compounds used in pharmaceutical composition for the treatment of schizophrenia and schizoaffective disorder, wherein, R═C10-C21 alkyl substituted by hydroxy or halogen.

  本公开涉及式（式 II）化合物的 C11-C22 烷酸帕潘立酮酯的羟基或卤素取代的新型衍生物及其制备工艺。所述化合物用于治疗精神分裂症和分裂情感障碍的药物组合物中，其中，R═C10-C21 烷基被羟基或卤素取代。
• NOVEL DERIVATIVES OF PALIPERIDONE AND PROCESS FOR THE PREPARATION THEREOF
  申请人：Zenvision Pharma LLP

  公开号：US20200354360A1

  公开（公告）日：2020-11-12

  The present disclosure relates to novel hydroxyl or halogen substituted derivatives of C 11 -C 22 alkanoic acid ester of Paliperidone compound of formula (formula II) and process for preparing the same. The said compounds used in pharmaceutical composition for the treatment of schizophrenia and schizoaffective disorder, wherein, R=C 10 -C 21 alkyl substituted by hydroxy or halogen.
• [F-18]labeling of 1,2-diacylglycerols
  作者：Toshihiro Takahashi、Tatsuo Ido、Shinji Nagata、Ren Iwata

  DOI：10.1002/1099-1344(200008)43:9<943::aid-jlcr379>3.0.co;2-v

  日期：2000.8

  We have developed two kinds of [F-18]labeled 1,2-diacylglycerols (1,2-DAGs) such as 1-(omega-[F-18]fluoroacyl)-2-acylglycerols (1*,2-[F-18]FDAGs) and 2-(omega-[F-18]fluoroacyl)-1-acylglycerols (1,2*-[F-18]FDAGs) for imaging receptor-mediated phosphatidyl-inositol (PI) turnover responses by positron emission tomography (PET). The 1*,2-[F-18]FDAGs were synthesized by the reaction of 2-monoacyl glycerols with omega-[F-18]fluoroacyl chlorides (method A) and 1-(16-[F-18]fluoro palmitoyl)-2-palmitoylglycerol (1*,2-[F-18]FDAG(C16,C16)) and 1-(8-[F-18]fluoro octanoyl)-2-palmitoylglycerol (1*,2-[F-18]FDAG(C8,C16)) were synthesized using method A. However, during the synthesis of 1,2*-[F-18]FDAGs, we adopted the hydrogenolysis to remove a benzyl group from 3-O-benzyl-2-(omega-[F-18]fluoroacyl)-1-acylglycerol, which was synthesized by the nucleophilic exchange reaction of 3-O-benzyl-2-(omega-bromoacyl)-1-acylglycerol with [F-18]F- (method B) and 2-(16-[F-18]fluoropalmitoyl)-1-palmitoylglycerol (1,2*-[F-18]FDAG(C16,C16)) and [F-18]fluorooctanoyl)-1-palmitoylglycerol (1,2*-[F-18]FDAG(C16,C8)) were produced using method B. The purified 1*,2-[F-18]FDAGs were obtained in radiochemical yields of 8-35 % (based on [F-18]F-) with radiochemical purities of > 97 % and the purified 1,2*-[F-18]FDAGs were in radiochemical yields of 5-15 % with radiochemical purities of > 95 %. The total synthesis time from the start of the reactive [F-18]F- production, including HPLC purification, was 100 - 135 min (method A) and 115 - 175 min (method B), respectively. It has already been used for more than 100 preparations of 1*,2-[F-18]FDAG(C16,C16), 1*,2-[F-18]FDAG(C8, C16), and 1,2*-[F-18]FDAG(C16,C16), 1,2*-[F-18]FDAG(C16,C8) for animal studies.