Intellectual Property Project

Brittney BlackburneCHE 243-300

4/29/14

Dronabinol is “medical marijuana”

Aka 'Tetrahydrocannabinol' (THC)

Antimietic Taken orally Side effects Brand names

Marinol®

What is Dronabinol?

What does it treat?

Nausea/vomiting Motion sickness Appetite Cancer effects Side effects from

other drugs

Chemistry of Dronabinol Molecular Formula: C21H30O2 Molecular Weight: 314.4617 Solubility: Soluble in ethanol Boiling point: 157 °C Other notes: Very low toxicity. Chemical

found naturally in cannabis. Represses neurotransmitters in the brain.

Patent Information Name of Patent: Synthetic route to dronabinol Purpose: To determine a novel synthetic route for creating the compound

dronabinol, which can be distributed as an antiemetic. Patent Number: 7,323,576 Inventors: Souza; Fabio E. S. (Mississauga, CA), Field; Jason E. (Mississauga,

CA), Pan; Ming (Mississauga, CA), Ramjit; Navindra J. (Mississauga, CA), Tharmanathan; Tharsika (Markham, CA), Jende-Tindall; Tracey (Aurora, CA)

Assignee: Alphora Research Inc. (Mississauga, Ontario, CA) Date of Filing: October 1, 2004 Date Patent Expires: October 1, 2024

Patent Information

Seven Dependent Claims Two independent claims:

1. A process for preparing Dronabinol by esterifying cis-(1R,2S)-2-hydroxy-4-methylcyclohex-3-ene carboxylic acid to form a lower alkyl ester. Then, subjecting the lower alkyl ester to a nucleophilic addition reaction with an appropriate organometallic compound to form cis-(3S,4R)-1-methyl-3-hydroxy-4-(2-hydroxyprop-2-yl) cyclohex-1-ene. Finally, reacting said product with olivetol (1,3-dihydroxy-5-n-pentylbenzene).

Patent Information

Seven Dependent Claims Two independent claims:

1. A process for preparing Dronabinol by esterifying cis-(1R,2S)-2-hydroxy-4-methylcyclohex-3-ene carboxylic acid to form a lower alkyl ester. Then, subjecting the lower alkyl ester to a nucleophilic addition reaction with an appropriate organometallic compound to form cis-(3S,4R)-1-methyl-3-hydroxy-4-(2-hydroxyprop-2-yl) cyclohex-1-ene. Finally, reacting said product with olivetol (1,3-dihydroxy-5-n-pentylbenzene).

Patent Information

2. A process of preparing dronabinol, which comprises the successive steps of: (a) reacting 2-methyl-3-butyn-2-ol with acetic anhydride under acidic conditions, followed by transition metal catalyzed rearrangement, to obtain 1-acetoxy-3-methyl-1,3-butadiene; (b) subjecting the product to Diels-Alder reaction with methyl acrylate to form methyl 2-acetoxy-4-methyl cyclohex-3-ene carboxylate; (c) isolating the racemic cis isomer of product from (b) by crystallization; (d) converting this carboxylate to racemic cis-2-hydroxy-4-methylcyclohex-3-ene carboxylic acid; (e) resolving the racemic mixture to obtain significantly enantiomerically enriched cis-2-hydroxy-4-methylcyclohex-3-ene carboxylic acid; (f) esterifying the resolved product from (e) to form a lower alkyl ester (g) reacting the lower alkyl ester with a methyl magnesium halide to form cis-menth-1-ene-3,8-diol; (h) reacting product from (g) with olivetol to form 1,3-dihydroxy-2-[(1R,6R)-6-(2-hydroxyprop-2-yl)-3-methylcyclohex-2-en-1-y- l]-5-n-pentylbenzene; and (i) cyclizing the product from (h) to obtain dronabinol.

Questions?

Sources

US Patent Office Medline Plus Pubchem