Synthesis of 11-nor-.DELTA.-9-tetrahydrocannabinol-9-carboxylic acid glucuronide
AssigneeSynthetic Technology Corporation
InventorsMarcus A. Tius, Mark R. Hagadone
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Abstract
A method of producing a deuterated or undeuterated 11-nor-.DELTA..sup.8 -tetrahydrocannabinol (THC) glucuronide or deuterated or undeuterated 11-nor-.DELTA..sup.9 -THC glucuronide by reacting a blocked THC carboxylic acid precursor with a blocked sugar epoxide precursor is disclosed. Also disclosed are: deuterated 11-nor-.DELTA..sup.8 - or .DELTA..sup.9 -THC carboxylic acid glucuronide having a deuterated hydrocarbon chain; 5'-deuterated 11-nor-.DELTA..sup.8 - or .DELTA..sup.9 -THC-carboxylic acid or 5'-deuterated .DELTA..sup.8 - or .DELTA..sup.9 -THC glucuronide. The compositions are useful as GC-MS standards; in methods for preparing antibodies reactive with a THC glucuronide; and, in GC-MS diagnostic methods for THC metabolites.
Claims6
A method of producing an 11-nor-.DELTA..sup.8 -THC glucuronide or 11-nor-.DELTA..sup.9 -THC glucuronide comprising:
- reacting a deuterated or undeuterated blocked .DELTA..sup.8 - or .DELTA..sup.9 -THC carboxylic acid precursor of the formula:
- ##STR5## wherein one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 comprises a carboxyl group;
- the remainder of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 comprise hydrogen, deuterium or one or more hydroxyl groups blocked by a protective agent selected from the group consisting of tert-butyl dimethyl silyl, tert-butyl dimethyl allyl, t-hexyldimethylsilyl, triethylsilyl, and tri-isopropylsilyl;
- .DELTA..sup.8 and .DELTA..sup.9 comprise different anomeric linkage in double bonding between the carbon atoms substituted with R.sub.1 and R.sub.2, or R.sub.2 and R.sub.3 ;
- and, R.sub.5 is a deuterated or undeuterated hydrocarbon chain comprising at least one carbon atom,
- with a dual-blocked sugar epoxide precursor of the formula:
- ##STR6## wherein R.sub.6 comprises a first protective agent selected from the group consisting of benzyl, methoxybenzyl, dimethoxybenzyl, cinnamyl, allyl, methallyl, trityl, fluorenyl, diphenylmethyl, phenylpropenyl and p-methoxyphenylmethyl groups, and R.sub.7 and R.sub.8 comprise a second protective agent selected from the group consisting of tert-butyl dimethyl silyl, tert-butyl dimethyl allyl, t-hexyldimethylsilyl, triethylsilyl, and tri-isopropylsilyl;
- and then removing the first and the second protective agents to obtain the 11-nor-.DELTA..sup.8 - or .DELTA..sup.9 -THC-carboxylic acid glucuronide.
Dependencies are inferred from the claim text.