Synthesis of Morphine Analogues - Study Chemistry with Lluís

Описание: Opioids are some of the most effective drugs for treating both acute and chronic pain. They include natural compounds like morphine and synthetic ones such as fentanyl. But as powerful as they are, opioids come with some serious downsides, things like addiction, respiratory depression, and constipation. These side effects often limit how much and how often doctors can use them safely.

Join me in a new series exploring the synthesis of morphine analogues. I’ll walk you through the synthesis route step-by-step, explain the reaction mechanisms behind each transformation, and highlight the important named reactions and conditions. Along the way there’ll be quick quizzes to test your knowledge. Subscribe and follow the series to learn the methods and master the name reactions.

Precisely, I describe the synthesis of carbamorphine, a version of morphine where the oxygen atom in the core was replaced with a methylene group. According to the authors, the idea was to keep the same overall shape of the molecule, but to see if this new analogue could still relieve pain, possibly with fewer side effects.


NROChemistry books:
1. The Chemists' Cookbook: https://nrochemistry.com/the-chemists...
2. Named Reactions Handbook & Quiz: https://nrochemistry.com/shop/named-r...
3. Named Reactions Handbook & Quiz, Volume 2 (waitlist): https://nrochemistry.com/named-reacti...


References:
1. Main article: PNAS 2025, 122, e2425438122. https://doi.org/10.1016/j.trechm.2019...
2. Bromination: Tetrahedron 2017, 73, 7105. https://doi.org/10.1016/j.tet.2017.10...
3. Heck Reaction: Trends Chem. 2019, 1, 572. https://doi.org/10.1016/j.trechm.2019...
4. Anhydrous Hydration: Org. Lett. 2009, 11, 5598. https://doi.org/10.1021/ol902309z
5. PDB ID of u-opioid receptor: 8EFB
6. PDB ID of morphine: 8EF6
7. Cephanolide natural products: J. Am. Chem. Soc. 2021, 143, 2710. https://doi.org/10.1021/jacs.1c00293
8. Poppy flower photos by Alex Belogub, Alyssa Morgan, and lorin Both on Unsplash.


List of opioids:
Oxycodone
Oxymorphone
Hydrocodone
Hydromorphone
Heroin
Fentanyl
Morphine
Codeine
Nalorphine
Naloxone