Iodine-mediated cyclization of cannabigerol (CBG) expands the cannabinoid biological and chemical space

Annalisa Lopatriello, Diego Caprioglio, Alberto Minassi, Aniello Schiano Moriello, Carmen Formisano, Luciano De Petrocellis, Giovanni Appendino, Orazio Taglialatela-Scafati

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Electrophilic attack to a double bond, the classic trigger of intramolecular isoprenoid cyclizations, is apparently silent in Cannabis and the diversity of the cannabinome can be ultimately traced to the oxidative cyclization of cannabigerolic acid (CBGA, 1a), a process triggered by the generation of an aromatic electrophilic species. To expand the chemical space of the cannabinoid chemotype, we have investigated an oxidative trigger based on the addition of iodine to the terminal isoprenyl double bond of cannabigerol (CBG, 1b), the decarboxylated and thermally stable version of CBGA (1a). Apart from the predictable product of an iodine-induced cascade cyclization (3), also a pair of unprecedented spiranes named spirocannabigerols (4a,b), derived from the formation of an edge-protonated cyclopropyl cation was also formed, along with a product (5) resulting from the incorporation, in a Friedel-Craft fashion, of the reaction solvent (toluene). Biological evaluation of these compounds on six thermo-transient receptor potential channels (TRPs) showed a remodeling of bioactivity compared to GBC, with emphasis on TRPA1 rather than TRPM8.

Lingua originaleInglese
pagine (da-a)4532-4536
Numero di pagine5
RivistaBioorganic and Medicinal Chemistry
Volume26
Numero di pubblicazione15
DOI
Stato di pubblicazionePubblicato - 15 ago 2018

Fingerprint

Entra nei temi di ricerca di 'Iodine-mediated cyclization of cannabigerol (CBG) expands the cannabinoid biological and chemical space'. Insieme formano una fingerprint unica.

Cita questo