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OTHER INFORMATION
Thebaine CAS number 115-37-7
The consumption of poppy seeds in various foods may lead to a positive
opiate result in urine subjected to testing for drugs of abuse. As a
natural constituent of poppy seeds, thebaine was investigated as a
possible marker for poppy seed consumption. Poppy seeds were examined
for opiate content by gas chromatography-ion trap mass spectrometry
(GC-MS) after extraction with methanol. Urine samples spiked with
thebaine and urine from subjects given 11 g of poppy seeds were tested
for the presence of thebaine, codeine, and morphine. Street heroin, one
morphine and one codeine tablet, and urine from individuals who had used
heroin were also examined for thebaine. Urine specimens were screened by
enzyme immunoassay (EMIT) and confirmed for thebaine by GC-MS using a
solid-phase extraction method. The GC-MS assay showed a linear response
over a range of 1-100 ng/mL and a limit of detection of 0.5 ng/mL.
Thebaine was detectable in the urine of poppy seed eaters in
concentrations ranging from 2 to 81 ng/mL. Because thebaine was absent
in powdered drugs and the urine of true opiate drug users, thebaine is
proposed as a direct marker for poppy seed use.
The 14-hydroxymorphinans, such as, oxycodone, naloxone, naltrexone,
nalbuphine and nalmefene are important opiate derivatives due to their
behavior as potent analgesics and/or narcotic antagonists. The most
practical synthetic routes to the preparation of these pharmaceuticals
have utilized the alkaloid, thebaine, as a starting material. Other
important opiate derivatives such as the ring-C bridged compounds
buprenorp ine and etorphine are also most practically prepared from
thebaine.
In accordance with one conventional process, thebaine is oxidized to
14-hydroxycodeinone by use of m-chloroperbenzoic acid in an acetic acid
trifluoroacetic acid mixture or by a mixture of hydrogen peroxide and
formic acid. 14-hydroxycodeinone is catalytically reduced to oxycodone.
Oxycodone is a product sold for use as and analgesic and its production
consumes large amounts of thebaine.
Oxycodone can be, in turn, O-demethylated with boron tribromide to yield
oxymorphone. After blocking of the hydroxyl groups with a suitable
blocking agent, such as, acetyl groups, the oxymorphone derivative is
reacted with cyanogen bromide in a von Braun demethylation to yield an
N-cyanodihydronormorphinone derivative that is thereafter hydrolyzed to
14-hydroxydihydronormorphinone (noroxymorphone). Noroxymoiphone can be
readily converted to nal-compounds by N-alkylation with appropriate
alkyl halide, or acylation with appropriate acyl halide or anhydrde,
followed by reduction. A more generally applicable process, converts the
oxycodone of the above process to noroxycodone by the von Braun N-dethylation
followed by conversion to a 3-O-methyl-nal-compound using Na-kylation
with an appropriate alkyl halide, or by alkylation with an appropnate
alkyl halide, or acylation with appropriate acyl halide or anhydride,
followed by reduction. The 3-O-methyl-nal-compound is reacted to a nal-compound
by O-demethylation.
One reason for the limited availability of thebaine, and its high cost,
is that total synthesis is difficult. U.S. Pat. Nos. 4,613,668 and
4,795,813 discuss the scarcity of thebaine and teach the total
synthesis, or alternative synthesis, of the 14-hydroxymorphinans. Yet,
the demand for thebaine remains.
A second reason for the limited availability of thebaine, and its high
cost, is that the primary source of thebaine is extraction from the
poppy plant, Papaver somniferum. Morphine is the major alkaloid that
accumulates in capsules of Papaver somniferum. Thus, the supply of
thebaine is to a great degree limited to some fraction of the demand for
morphine.
Further synthetic routes to the preparation of the 14-hydroxymorphinans
are known using the alkaloid, oripavine, as a starting material.
Oripavine has not been used as a starting material for the
14-hydroxymorphinans in any practical sense because it is not
recoverable from Papaver somiferum in any practical yield. Thus, there
is now no real shortage of this material, but only because there has
never developed any demand for it.
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India
