<Δ⁹-THC chloroformate> | 82459-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: <Δ⁹-THC chloroformate>
• 英文别名: (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-yl carbonochloridate；[(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-yl] carbonochloridate
• CAS: 82459-42-5
• 化学式: C₂₂H₂₉ClO₃
• 分子量: 376.923
• InChiKey: ZQMLAHSRPCMYPE-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.77
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  <Δ⁹-THC chloroformate> 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以51%的产率得到
  参考文献：
  名称：

  Synthesis of rotationally restricted tetrahydrocannabinol ethers

  摘要：

  Two rotationally restricted tetrahydrocannabinol (THC) ethers were synthesized to test the concept that the psychopharmacological activity of cannabinoids derives, in part, from the orientation of the lone pairs of electrons of the phenolic hydroxyl oxygen. These compounds, O,2-propano-DELTA-8-THC (3) and O,10-methano-DELTA-9-THC (12), lock the orientation of the lone pairs of electrons toward and away from the cyclohexene ring, respectively, by restricting bond rotation through the formation of cyclic ethers. The synthesis of 3 was achieved by alkylation of the phenolic oxygen of DELTA-8-THC (1) with 3-bromo-1-propanol followed by cyclodehydration in the presence of phosphorus pentoxide. The synthesis of 12 was achieved from a sequence of reactions that involved the cyclization of a chloroformate in a modification of the Darzens acylation of olefins. Thus, treatment of DELTA-9-THC with phosgene in the presence of N,N-dimethylaniline afforded DELTA-9-THC chloroformate. Subsequent intramolecular cycloaddition of the chloroformyl moiety to the DELTA-9-unsaturation in the presence of AlCl3 afforded the corresponding beta-chloro ester 9. Treatment of 9 with lithium aluminum hydride gave 10-(hydroxymethyl)-DELTA-9-THC (10). Compound 12 and 10-methylene-DELTA-8-THC (11) were obtained as a readily separable mixture by treatment of 10 with 3 mol of tosyl chloride in pyridine. C-13 NMR and H-1 NMR spectral assignments were made. A model study of the TiCl4-mediated cleavage of the MEM ether of phenol demonstrated generation of the phenoxymethyl cation.

  DOI：

  10.1021/jo00004a039
• 作为产物：
  描述：

  光气 、 四氢大麻酚 在 N,N-二甲基苯胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 22.0h， 以94%的产率得到<Δ⁹-THC chloroformate>
  参考文献：
  名称：

  Synthesis of rotationally restricted tetrahydrocannabinol ethers

  摘要：

  Two rotationally restricted tetrahydrocannabinol (THC) ethers were synthesized to test the concept that the psychopharmacological activity of cannabinoids derives, in part, from the orientation of the lone pairs of electrons of the phenolic hydroxyl oxygen. These compounds, O,2-propano-DELTA-8-THC (3) and O,10-methano-DELTA-9-THC (12), lock the orientation of the lone pairs of electrons toward and away from the cyclohexene ring, respectively, by restricting bond rotation through the formation of cyclic ethers. The synthesis of 3 was achieved by alkylation of the phenolic oxygen of DELTA-8-THC (1) with 3-bromo-1-propanol followed by cyclodehydration in the presence of phosphorus pentoxide. The synthesis of 12 was achieved from a sequence of reactions that involved the cyclization of a chloroformate in a modification of the Darzens acylation of olefins. Thus, treatment of DELTA-9-THC with phosgene in the presence of N,N-dimethylaniline afforded DELTA-9-THC chloroformate. Subsequent intramolecular cycloaddition of the chloroformyl moiety to the DELTA-9-unsaturation in the presence of AlCl3 afforded the corresponding beta-chloro ester 9. Treatment of 9 with lithium aluminum hydride gave 10-(hydroxymethyl)-DELTA-9-THC (10). Compound 12 and 10-methylene-DELTA-8-THC (11) were obtained as a readily separable mixture by treatment of 10 with 3 mol of tosyl chloride in pyridine. C-13 NMR and H-1 NMR spectral assignments were made. A model study of the TiCl4-mediated cleavage of the MEM ether of phenol demonstrated generation of the phenoxymethyl cation.

  DOI：

  10.1021/jo00004a039

文献信息

• SELTZMAN, HERBERT H.;HSIEH, YUNG-AO;PITT, COLIN G.;REGGIO, PATRICIA H., J. ORG. CHEM., 56,(1991) N, C. 1549-1553
  作者：SELTZMAN, HERBERT H.、HSIEH, YUNG-AO、PITT, COLIN G.、REGGIO, PATRICIA H.

  DOI：——

  日期：——
• [EN] ENDOCANNABINOID SYSTEM-TARGETING PRODRUGS AND THERAPEUTIC USES THEREOF<br/>[FR] PROMÉDICAMENTS CIBLANT UN SYSTÈME ENDOCANNABINOÏDE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：[en]MEDIPURE PHARMACEUTICALS INC.

  公开号：WO2022213200A1

  公开（公告）日：2022-10-13

  The present invention relates to a process preparing and therapeutic use of endocannabinoid-targeting prodrugs in a delivery system. In particular, the present invention relates to prodrugs of the endocannabinoid system- targeting molecules cannabidiol (CBD), cannabigerol (CBG), tetrahydrocannabinol (THC) and cannabichromene (CBC) for oral, transmucosal, transdermal and parental administration, and methods and uses of the same as therapeutics, wherein the prodrugs have the formulae (Ia), (Ib), (Ic), or (Id).