Cascade 1 - synthesis of cannabinoid derivatives

Readily accessible geranyl halides and derivatives thereof will be coupled, using Pd-catalyzed cross-coupling reactions, to olivetolic acid which contains an additional halide substituent at the aromatic ring. Initially, Suzuki or Negishi type coupling reactions will be used in which the geranyl partner is converted into a borinate ester or organozinc compound. Then differently substituted olivetolic acid derivatives will be prepared and coupled to the geranyl derivatives. The final step in the biosynthesis of THC in Cannabis sativa is the ring-closure and subsequent decarboxylation of canna¬bigerolic acid. This unique oxidative cyclization reaction is catalyzed by Δ1-tetrahydrocannabinolic acid synthase (THCAS). The effectiveness of the coupling procedure will be evaluated in close collaboration with ESR Y (WP1) under three conditions: non-compartmentalized, in polymersomes, and in Pickering emulsions