(O,2-propano-Δ⁸-THC) | 131351-99-0

• 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: (O,2-propano-Δ⁸-THC)
• 英文别名: (8aR,12aR)-8,8,11-trimethyl-5-pentyl-3,4,8a,9,12,12a-hexahydro-2H-isochromeno[3,4-h]chromene
• CAS: 131351-99-0
• 化学式: C₂₄H₃₄O₂
• 分子量: 354.533
• InChiKey: XUVBINQIGUQQJP-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (O,2-propano-Δ⁸-THC) 在 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 对二甲苯 、 potassium carbonate 、 对甲苯磺酸 、 potassium hexacyanoferrate(III) 作用下， 以 甲醇 、 异丙醇 、 叔丁醇 、 苯 为溶剂， 反应 61.0h， 生成 (8aR,12aR)-8,8-dimethyl-5-pentyl-3,4,8a,9,12,12a-hexahydro-2H-isochromeno[3,4-h]chromene
  参考文献：
  名称：

  Importance of the C-1 Substituent in Classical Cannabinoids to CB₂ Receptor Selectivity:  Synthesis and Characterization of a Series of O,2-Propano-Δ⁸-tetrahydrocannabinol Analogs

  摘要：

  The separation of the mood-altering effects of cannabinoids from their therapeutic effects has been long sought. Results reported here for a series of C-9 analogs of the cyclic ether O,2-propano-Delta(8)-tetrahydrocannabinol (O,2-propano-Delta(8)-THC) point to the C-1 position in classical cannabinoids as a position for which CB2 subtype selectivity occurs within the cannabinoid receptors. O,2-Propano-11-nor-Delta(8)-THC, O,2-propano-Delta(9,11)-THC, O,2-propano-9-oxo-11-norhexahydrocannabinol (O,2-propano-9-oxo-11-nor-HHC), and O,2-propane-9 alpha- and O,2-propane-9 beta-OH-11-nor-HHC were synthesized and evaluated in radioligand displacement assays for affinity at the CB1 and CB2 receptors and in the mouse vas deferens in vitro assay and the mouse tetrad in vivo assay for cannabinoid activity. Evaluation of binding affinity at the CB1 and CB2 receptors revealed that each compound possesses a modest increased affinity for the CB2 receptor. Analogs which contained an oxygen attached to C-9 (i.e., oxo and hydroxy derivatives) showed the highest affinity and selectivity for CB2 (for O,2-propano-9-oxo-11-nor-HHC, K-i(CB1) = 90 nM, K-i(CB2) = 23 nM, selectivity ratio 3.9; for O,2-propano-9 beta-OH-11-nor-HHC, K-i(CB1) = 26 nm, K-i(CB2) = 5.8 nM, selectivity ratio 4.5). Each compound was found to produce a dose-dependent inhibition of electrically-evoked contractions of the mouse isolated vas deferens when administered at submicromolar concentrations. This inhibition could readily be prevented by the selective CB1 cannabinoid receptor antagonist SR-141716A. The analogs exhibited unique in vivo profiles with O,2-propano-Delta(9,11)-THC exhibiting antinociception with reduced activity in three other in vivo measures and O,2-propano-9 beta-OH-HHC exhibiting lack of dose responsiveness in all measures. The CB2 selectivities of the O,2-propano analogs may be due to differences in salvation/desolvation that occur when the ligands enter the CB1 vs CB2 binding site. Alternatively, the CB2 selectivities may be the result of an amino acid change from a hydrogen bond-accepting residue in CB1 to a hydrogen bond-donating residue in CB2.

  DOI：

  10.1021/jm970136g
• 作为产物：
  描述：

  (-)-Δ8-四氢大麻酚 在 phosphorus pentoxide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 苯 为溶剂， 反应 17.5h， 生成 (O,2-propano-Δ⁸-THC)
  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：——