ArticleNature communications2021
Site selective C-H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Atypical respiration patterns of kratom alkaloids.The Journal of pharmacology and experimental therapeutics · 2026Article
- Investigating Opioid Receptor Activity through Biocatalytic Halogenation and Oxidation of Mitragynine.ACS chemical biology · 2026Article
- Indole Alkaloids as Biased Opioid Receptor Modulators.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Semi-synthesis in the exploration of opioid-targeting natural products.Natural product reports · 2025Review
- Total synthesis and biological activity of "carbamorphine": O-to-CHProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure-guided design of partial agonists at an opioid receptor.Nature communications · 2025Article
- Enhanced transdermal delivery of lidocaine cream via ultrasound and microneedle rollers.Frontiers in bioengineering and biotechnology · 2025Article
- Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models.Nature communications · 2024Article
- Signaling Modulation Mediated by Ligand Water Interactions with the Sodium Site at μOR.ACS central science · 2024Article
- Structure-Guided Design of Partial Agonists at an Opioid Receptor.Research square · 2024Article
- A Platform for the Synthesis of Corynantheine-Type Corynanthe Alkaloids.Journal of the American Chemical Society · 2024Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine DJournal of medicinal chemistry · 2023Article
- Catalytic Antibody Blunts Carfentanil-Induced Respiratory Depression.ACS pharmacology & translational science · 2023Article
- Modified Akuamma Alkaloids with Increased Potency at the Mu-opioid Receptor.Journal of medicinal chemistry · 2023Article
- Pharmacological Mechanism of the Non-hallucinogenic 5-HTACS chemical neuroscience · 2023Article
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine.British journal of pharmacology · 2022Article
- Physiological dependence to mitragynine indicated by a rapid cross-dependence procedure with heroin-dependent mice.Psychopharmacology · 2022Article
- Total Synthesis of (-)-Kopsifoline A and (+)-Kopsifoline E.Organic letters · 2021Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Mitragynine (MG) is the most abundant alkaloid component of the psychoactive plant material "kratom", which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method for selective functionalization of the unexplored C11 position of the MG scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. Through this work we discover that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. 7-Hydroxymitragynine (7OH), the parent compound with low efficacy on par with buprenorphine, is transformed to an even lower efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.