Project description
Synthetically manufacturing noroxymorphone
Opioids, like morphine, are a class of drugs derived from or simulating natural substances found in poppy plants. Often prescribed for pain relief, opioids can be extremely addictive, resulting in abuse and potentially fatal overdoses. The latter can be treated with certain nal compounds that act as opioid antagonists. Noroxymorphone, a key late-stage intermediate in the synthesis of opioid antagonists, is currently manufactured semi-synthetically from poppy-derived compounds. The process, however, is relatively wasteful and inefficient, not to mention that poppy cultivation is problematic due to its association with illicit narcotics. Supported by the Marie Skłodowska-Curie Actions programme, the NOROXYSYN project aims to develop a short-step method for synthesising noroxymorphone from inexpensive feedstock that can be scaled up for industrial manufacture.
Objective
Opiates, derived from the poppy plant and exemplified by morphine, are important medicines for pain and other disorders because of their agonistic action on the opioid receptors. However, many opiates have bad side effects such as respiratory depression, sedation, and constipation. They can be highly addictive, which leads to abuse and overdose deaths.
To address these issues, “nal-compounds” have been developed, which attenuate the effects of opioid receptor agonists, making them useful for treating opioid overdose and abuse; examples include the World Health Organization essential medicines naloxone and naltrexone, which are µ-opioid receptor antagonists. Other nal-compounds include nalbuphine, nalmefene, and nalfurafine, which have a range of clinical uses. Noroxymorphone is a common late-stage intermediate in the synthesis of nal-compounds, which makes its synthesis a critical task.
Noroxymorphone is manufactured semisynthetically from the poppy-derived compounds oripavine and thebaine. However, the quantity of oripavine and thebaine in poppies is low compared to the most abundant compound morphine. In addition, poppy cultivation is problematic; it is highly space- and resource-intensive, and could be affected by floods, droughts, disease, and geopolitics. Illegal poppy diversion also fuels the illicit narcotic trade (e.g. heroin), resulting in huge societal problems. Therefore, breaking human reliance on the poppy by developing an industrially viable total synthesis of noroxymorphone from inexpensive feedstocks would be game-changing.
Dozens of total syntheses of morphine and related compounds are already known, including one synthesis of noroxymorphone. However, none are remotely competitive with semisynthesis from poppy raw materials because of their step-count. In this MSCA Fellowship, we will use modern synthetic methods to develop a short (7/8 steps) lab-scale synthesis of noroxymorphone that is suitable for optimization for industrial manufacture.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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NG7 2RD Nottingham
United Kingdom
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