RT Journal Article
T1 The dimerization of Delta(9)-tetrahydrocannabinolic acid A (THCA-A)
A1 Cuadari, Arben
A1 Pollastro, Federica
A1 Unciti-Broceta, Juan D.
A1 Caprioglio, Diego
A1 Minassi, Alberto
A1 Lopatriello, Annalisa
A1 Munoz, Eduardo
A1 Taglialatela-Scafati, Orazio
A1 Appendino, Giovanni
K1 Phytocannabinoids
K1 Dimerization
K1 Delta(9)-tetrahydrocannabinolic acid A
K1 Delta(9)-tetrahydrocannabinol
K1 PPAR-gamma
K1 Salsalate
K1 Drug
AB The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and antidiabetic agents provided a rationale to investigate the dimerization of the substituted salicylate Delta(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 Delta(9)-THC upon heating. However, only the didepsidic dimer 5 activated PPAR-gamma, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases. (C) 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. 
PB Inst materia medica, chinese acad medical sciences
PB Elsevier
SN 2211-3835
YR 2019
FD 2019-05-15
LK http://hdl.handle.net/10668/18708
UL http://hdl.handle.net/10668/18708
LA en
NO Cuadari A, Pollastro F, Unciti-Broceta JD, Caprioglio D, Minassi A, Lopatriello A, et al.  The dimerization of Δ9-tetrahydrocannabinolic acid A (THCA-A). Acta Pharm Sin B. 2019 Sep;9(5):1078-1083
NO We are grateful to MIUR (Ministero Universita’ e Ricerca) for financial support to the groups in Novara and Naples (PRIN2017, Project 2017WN73PL, bioactivity-directed exploration of the phytocannabinoid chemical space, Italy). Eduardo Mun˜oz, Juan D. Unciti-Broceta and Giovanni Appendino were also supported by Emerald Health Biotechnology Espan˜a (Spain).
DS RISalud
RD Apr 7, 2025