Synthesis of nine potential synthetic cannabinoid metabolites with a 5F-4OH pentyl side chain from a scalable key intermediate

Wu, Xiongyu; Bopp, Daniel; Wallgren, Jakob; Dahlén, Johan; Konradsson, Peter

doi:10.1080/00397911.2020.1854786

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…The Friedel–Crafts method relies on electrophilic aromatic substitution reactions, where desired cannabinoids are formed through the reaction of aromatic compounds with electrophiles. All these methods require quality control, analysis, and specialized knowledge to ensure the purity and compliance of the obtained cannabinoids with specific standards [ 7 , 8 , 9 ].…”

Section: Methods Of Obtaining Cannabinoidsmentioning

confidence: 99%

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases—A Synthetic Review

Kwiecień,

Kowalczuk

2023

Molecules

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Dermatological diseases pose a significant burden on the quality of life of individuals and can be challenging to treat effectively. In this aspect, cannabinoids are gaining increasing importance due to their therapeutic potential in various disease entities including skin diseases. In this synthetic review, we comprehensively analyzed the existing literature in the field of potential dermatological applications of a lesser-known subgroup of cannabinoids, the so-called minor cannabinoids, such as cannabidivarin (CBDV), cannabidiforol (CBDP), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabielsoin (CBE), cannabimovone (CBM) or cannabinol (CBN), while drawing attention to their unique pharmacological properties. We systematically searched the available databases for relevant studies and analyzed the data to provide an overview of current thematic knowledge. We looked through the full-text, bibliographic and factographic databases, especially Scopus, Web of Science, PubMed, Polish Scientific Journals Database, and selected the most relevant papers. Our review highlights that minor cannabinoids exhibit diverse pharmacological activities, including anti-inflammatory, analgesic, antimicrobial, and anti-itch properties. Several studies have reported their efficacy in mitigating symptoms associated with dermatological diseases such as psoriasis, eczema, acne, and pruritus. Furthermore, minor cannabinoids have shown potential in regulating sebum production, a crucial factor in acne pathogenesis. The findings of this review suggest that minor cannabinoids hold therapeutic promise in the management of dermatological diseases. Further preclinical and clinical investigations are warranted to elucidate their mechanisms of action, determine optimal dosage regimens, and assess long-term safety profiles. Incorporating minor cannabinoids into dermatological therapies could potentially offer novel treatment options of patients and improve their overall well-being.

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Section: Methods Of Obtaining Cannabinoidsmentioning

confidence: 99%

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases—A Synthetic Review

Kwiecień,

Kowalczuk

2023

Molecules

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“…An effective method to clarify the position of the hydroxyl group is by matching to a reference standard synthesized by different positional isomers under their separable chromatographic conditions. For example, reference standards have been prepared for synthetic cannabinoids in which hydroxyl groups have been introduced into the adamantyl moiety, pentyl or 5‐fluoro pentyl side chain, or the terminal alkene on the pentyl side chain 14–18 . However, there are no reports on the preparation of synthetic cannabinoids with hydroxyl groups introduced at the cumyl moiety.…”

Section: Introductionmentioning

confidence: 99%

“…For example, reference standards have been prepared for synthetic cannabinoids in which hydroxyl groups have been introduced into the adamantyl moiety, pentyl or 5-fluoro pentyl side chain, or the terminal alkene on the pentyl side chain. [14][15][16][17][18] However, there are no reports on the preparation of synthetic cannabinoids with hydroxyl groups introduced at the cumyl moiety.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and structure determination of a synthetic cannabinoid CUMYL‐THPINACA metabolite with differentiation between the ortho‐, meta‐, and para‐hydroxyl positions of the cumyl moiety

Azuma

Doi

Asada

et al. 2023

Drug Testing and Analysis

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Synthetic cannabinoids, a type of new psychoactive substances, are likely to be rapidly metabolized; thus, the detection of their metabolites, rather than the parent compound, is a common method used to prove drug consumption. Although the analysis of metabolites is generally performed by mass spectrometry, it is limited to structural estimation because of few commercially available standards. In particular, distinguishing between positional isomers is difficult. Synthetic cannabinoids with a cumyl moiety can be hydroxylated at the cumyl moiety during metabolism, but it remains unclear whether the hydroxylation occurs at the ortho, meta, or para position. This study determined the structures of a metabolite formed by mono‐hydroxylation at the cumyl moiety of the synthetic cannabinoid CUMYL‐THPINACA, used as a model compound. Chemical synthesis was performed to create possible metabolites with one hydroxyl group at the ortho, meta, or para positions of the cumyl moiety. Using the synthesized metabolites and liquid chromatography‐quadrupole time‐of‐flight mass spectrometry, the metabolite detected in the microsomal reaction of CUMYL‐THPINACA was identified as a compound mono‐hydroxylated at the para position based on retention time and product ion spectra. Moreover, the rapid metabolism of CUMYL‐THPINACA was demonstrated with an in vitro half‐life of 4.9 min and the identified metabolite could be detected for a relatively long time in vitro. The synthesized metabolite may be utilized as a good reference standard for proof of CUMYL‐THPINACA consumption. These findings have potential applications in the synthesis of metabolites of other synthetic cannabinoids bearing a cumyl moiety.

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Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F‐MDMB‐PICA

Chen,

Zhang,

Yang

et al. 2024

Drug Testing and Analysis

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Abstract5F‐MDMB‐PICA, an indole‐type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F‐MDMB‐PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F‐MDMB‐PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high‐resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography–tandem mass spectrometry and ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F‐MDMB‐PICA uptake.

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Synthesis of nine potential synthetic cannabinoid metabolites with a 5F-4OH pentyl side chain from a scalable key intermediate

Cited by 4 publications

References 21 publications

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases—A Synthetic Review

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases—A Synthetic Review

Synthesis and structure determination of a synthetic cannabinoid CUMYL‐THPINACA metabolite with differentiation between the ortho‐, meta‐, and para‐hydroxyl positions of the cumyl moiety

Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F‐MDMB‐PICA

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