Description:
The Invention:
Developed an innovative method to convert caraway-derived (+)-carvone (1, $0.15/g) into (–)- isopiperitenol (3, $1000/g) – a critical intermediate that was previously employed in the synthesis (+)-ent-CBD [(+)-5, Scheme 1]. Of note, this four step process (1 to 3) can be performed on multi-gram scale and relies on the one-pot borane reduction / thermal rearrangement of an α,β−unsaturated hydrazone as a key step. By uniting the synthetic (–)- isopiperitenol with olivetol derivatives (Ar-H) under buffered Lewis acid conditions, Maio lab successfully prepared a small library of non-natural, enantiomer (mirror image) CBD derivatives, each tailored with different alkyl chain lengths [(+)-ent-4 to (+)-ent-8, R = C3H7 to C8H17]. While the derivatives with an odd number of alkyl carbons are known in their natural form [(–)-4, (–)-5, and (–)-7], two of these enantiomers, (+)-ent-4 and (+)-ent-7, had not been previously disclosed. More importantly, compounds (+)-ent-6 and (+)-ent-8, featuring an even number of alkyl carbons, had never been previously reported in either enantiomer form.
In addition to the novel compositions and methods for their synthesis, we have also obtained data for methods of use of cannabidiol congeners for multiple downstream clinical applications based on our preclinical studies in the Hines group laboratories.
Benefits:
- Increased affinity for the CB1 and CB2 receptors, enhanced clinical efficacy
- Novel therapeutics for the treatment of epilepsy, anxiety, and / or disorders with an inflammatory component including neurodegenerative conditions and psychiatric conditions, as well as pain and arthritis
Market Opportunity:
As mentioned above, this method aims to assist various clinical indications such as seizures. The market for Epilepsy treatment, according to The Epilepsy Agency, is “USD 2.61 billion in 2021 and expected to reach USD 4.70 billion by 2030, at a Compound Annual Growth Rate (CAGR) of 8.35% during the forecast period”. Additionally, the Epilepsy treatment market is also expected to grow to $7.76B in 2022 and is expected to grow at a CAGR of 4.1% from 2022 to 2030.
Intellectual property:
- Preclinical stage, ready to move to Investigational New Drug