The dimerization of ⊿9-tetrahydrocannabinolic acid A (THCA-A)

• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2019,（5）
• 所属期刊栏目: Short Communication
• 页码范围: 1078-1083
• 页数: 6页
• 语种: 英文

摘要

The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and antidiabetic agents provided a rationale to investigate the dimerization of the substituted saticylate ⊿9-tetrahydrocannabinolic acid (THCA-A,3a) as a strategy to solve its instability to decarboxylation and to generate analogues and/or pro-drugs of this native pre-cannabinoid.Activation of the carboxylic group with the DCC-HOBt-DMAP protocol afforded a high yield of the OBt ester 4,that was next converted into the highly crystalline di-depsidic dimer 5 upon treatment with DMAP.The mono-depsidic dimer 6 was also formed when the reaction was carried out with partially decarboxylated THCA-A samples.The structure of the depsidic dimers was established by spectroscopic methods and by aminolysis of 5 into the pre-cannabinoid amide 7.Both dimers showed excellent shelf stability and did not generate significant amounts of ⊿9-THC upon heating.However,only the didepsidic dimer 5 activated PPAR-γ,the major target of pre-cannabinoids,but strong binding to serum proteins abolished this activity,also shielding it from the action of esterases.