As of 2018, over 500 natural products have been isolated and characterized from the Cannabis Sativa plant, many of which have shown interesting biological acitvity1. The most popular bioactive compounds are a part of the distinctive phytocannabinoid class, Δ9-THC, CBD, CBG, and CBC. Apart from this class, the Cannabis Sativa plant also contains many natural products belonging to terpenes, alkaloids, and flavonoids classes. Cannflavins A, B, and C, belonging to the flavonoids class, are characteristic of Cannabis Sativa. These prenylated (B) and geranylated (A and C) flavonoids, first isolated in 19802a and 20082b, showed interesting bioactivity in a different field. Initially, a mixture of Cannflavins A and B was used as an anti-inflammatory in vitro and showed that the combination was 30 times more potent than Aspirin3. Another report also showed the neuro-protective capacity of Cannflavin A by inhibiting Aβ fibrillisation4. So far, only Cannflavin B was synthesized in 7 steps with an overall yield of 11.5%5. Previous attempts to synthesize Cannflavin A using a similar approach failed, requiring a new approach to selectively synthesize these compounds. Herein, we report a de novo synthesis of Cannflavin A and additionally its regioisomer Cannflavin C in 12 steps in 8.4% and 5.3% overall yield respectively. The novel synthesis of those molecules allowed the preparation of a library of analogs in a divergent fashion via a late-stage cross-coupling. We also show the possibility to use the same synthetic strategy to provide more complexes and larger biflavonoids natural products. Recently, efforts are focused on developing a more concise and eco-friendly synthesis of these compounds.

First total syntheses of cannflavins A,C and synthesis of cannflavin B

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.