N‐Demethylation of Alkaloids

Thavaneswaran, Shanti; McCamley, Kristy; Scammells, Peter J.

doi:10.1002/chin.200738246

Cited by 9 publications

(14 citation statements)

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“…For our purpose the desired normorphine derivatives (normorphine (1), dihydronormorphine (2), norcodeine (3), dihydronorcodein (4), noroxymorphone (5) and noroxycodone (6) (Figure 1)) could be obtained by the N-demethylation of the starting molecules [6][7][8][9][10][11][12]. Codeine or dihydrocodeine can be N-demethylated with α-chloro-ethyl chloroformate in 1,2dichloroethane solvent and the intermediate carbamate was heated with methanol to yield the hydrochloride salt of norcodeine (dihydronorcodeine) (Scheme 1).…”

Section: Methodsmentioning

confidence: 99%

Vaccines against Drug Abuse: Morphine-Hapten Design and Synthesis

Köteles

Hosztafi

2019

The 23rd International Electronic Conference on Synthetic Organic Chemistry

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Drugs of abuse are small molecules that typically do not induce an antibody response following the administration. To induce antibodies against these kind of molecules, structural changes have to be made to obtain so called “haptens”. The hapten must be coupled to immunogenic proteins, called “carriers”. These connected derivatives are typically drug-linker adducts, in which the linker has a terminal functional group (i.e., carboxylic acid or aliphatic amine) that forms a covalent bond with the carrier. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Six nor-normorphine compounds were reacted with ethyl acrylate and ethyl bromoacetate. After the synthesis of the specific esters we hydrolyzed them to receive the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives. The next step was the coupling phase with glycine ethyl ester, but the reactions didn’t work or the work-up process was not accomplishable. As an alternative route the normorphine-compounds were reacted with N-chloroacetyl glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine sidechain. All of the glycine ester and the glycine carboxylic acid derivatives are under biological tests.

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Section: Methodsmentioning

confidence: 99%

Vaccines against Drug Abuse: Morphine-Hapten Design and Synthesis

Köteles

Hosztafi

2019

The 23rd International Electronic Conference on Synthetic Organic Chemistry

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“…[107] The growing consumption of buprenorphine in recent years is mainly the result of its extended use in detoxification and substitution programmes to treat opioid dependence. In 2009, global production reached a peak level of 6.5 tonnes.…”

Section: Buprenorphinementioning

confidence: 99%

Pharmaceuticals

Schaefer

2014

Natural Products in the Chemical Industry

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A boy who is born in Germany today has a probable life expectancy of around 77 years, and a girl one of 82 years -twice as long as in the year 1880. This increase is a consequence of both, better living circumstances -working conditions, food, clothing, housing -, and also a result of more comprehensive medical care. Thus, a whole range of infectious diseases has been wiped out, or brought at least under control, and the mortality rate for civilisation-and age-related diseases has dropped. Vaccinations and drugs play a key role in this outcome. The 20th century is characterised especially by the worldwide blossoming of the pharmaceutical industry. More and more, the targeted search for and development of new drugs have replaced serendipitous discoveries (Fig. 5.1). Pharmaceuticals of the last century.

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“…There are many methods for the N‐demethylation of alkaloids. Only a few of them are applied for 14‐hydroxy opioids . Traditionally, N‐demethylation is accomplished by refluxing the substrate solution with more than five equivalents of chloroformate over several hours (Scheme B), resulting in the nor‐compounds with moderate to good yields after hydrolysis .…”

Section: Introductionmentioning

confidence: 99%

Organophotocatalytic N‐Demethylation of Oxycodone Using Molecular Oxygen

Chen

Glotz

Cantillo

et al. 2020

Chemistry A European J

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N‐Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable organophotocatalytic procedure that accomplishes the N‐demethylation step using molecular oxygen as the terminal oxidant and an organic dye (rose bengal) as an effective photocatalyst. Optimization of the reaction conditions under continuous flow conditions using visible‐light irradiation led to an efficient, reliable, and scalable process, producing noroxycodone hydrochloride in high isolated yield and purity after a simple workup.

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N‐Demethylation of Alkaloids

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 9 publications

References 1 publication

Vaccines against Drug Abuse: Morphine-Hapten Design and Synthesis

Vaccines against Drug Abuse: Morphine-Hapten Design and Synthesis

Pharmaceuticals

Organophotocatalytic N‐Demethylation of Oxycodone Using Molecular Oxygen

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