Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

Carreras, Javier; Kirillova, Mariia S.; Echavarren, Antonio M.

doi:10.1002/anie.201601834

Cited by 30 publications

(28 citation statements)

References 59 publications

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“…[20] Furthermore,t he optical rotation of 6 ([a] 22 D =+40.68 8 (c = 0.29, CHCl 3 )) was very different to that reported ([a] 22 D = À178 8 (c = 0.02, CHCl 3 )). [9] Thes tructure of anhydrocannabimovone (6)w as finally confirmed by X-ray diffraction [19] and its absolute configuration was assigned on the basis of the X-ray structure of anhydrocannabimovone 2-bromobenzoate (23; Figure 2). [19] In order to clarify the discrepancy between our structural assignment and that originally reported, [9] we performed DFT calculations to study the oxy-Michael cyclization.…”

Section: Angewandte Chemiementioning

confidence: 79%

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Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

2016

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The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of ah ighly stereoselective gold(I)-catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone.The herbaceous plant Cannabis sativa has been used in medicine for centuries and still attracts significant interest due to the biological and pharmaceutical activity of many of its metabolites.[1] More than 60 compounds,k nown as cannabinoids (a group of C 21 terpenophenolic compounds), are exclusively found in Cannabis sativa.[2] Owing to the development of synthetic cannabinoids, [3, 4] theunique components of Cannabis sativa are known as phytocannabinoids.T he most abundant compound is D 9-tetrahydrocannabinol (THC, 1; Figure 1), which shows interesting pharmacological activity as an analgesic,a ntiemetic,a nd appetite stimulant, among others,b esides its well-known psychotropic effects.[5] Several total syntheses of 1 have been accomplished to date. [6] Cannabidiol (CBD, 2)isanother important phytocannabinoid with great potential as ad rug [7] since it modulates the undesired effects of THC when they are administrated together. [8] As tructurally different cannabinoid named cannabimovone (3)h as recently been isolated by the groups of Taglialatela-Scafati and Appendino from an onpsychotropic variety of hemp (Cannabis sativa L.;F igure 1). [9] In their attempt at preparing 3 from CBD (2)t hrough an intramolecular aldol reaction of keto aldehyde 4 under mild acidic conditions,the product of dehydration (5)was formed instead (Scheme 1). Under basic conditions,t he novel cannabinoid anhydrocannabimovone (6)w as directly formed through an intramolecular oxy-Michael addition of one of the phenol groups to the intermediate enone.Synthetic 6 was found to be active against metabotropic and ionotropic cannabinoid receptors,s howing as imilar biological profile to THC, whereas cannabimovone (3)h as affinity only for ionotropic receptors. [9] Theunprecedented abeo-menthane terpenoid structure of cannabimovone (3)i ncludes ad ensely functionalized cyclopentane with four contiguous stereocenters.T he novel structure of 3,c oupled with its lability towards dehydration under acidic or basic conditions and the interesting biological profiles of both 3 and 6,i nspired us to develop at otal synthesis that could allow access to aw ide variety of Scheme 1. Synthesis of anhydrocannabimovone( 6)f rom cannabidiol (CBD, 2).[9][*] Dr.J .C arreras, M.

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Section: Angewandte Chemiementioning

confidence: 79%

“…Them olecular structure of 21 was determined by X-ray diffraction, which confirmed the relative configuration between the isopropenyl and the hydroxyethyl substituents. [19] Treatment of 21 with ZnI 2 effected ap inacol rearrangement to give ketone 17.…”

Section: Angewandte Chemiementioning

confidence: 99%

Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

2016

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“…Its total synthesis was reportedb yE chavarren et al,w ho used ac oupling-first-and-manipulation-later strategy (Scheme 20). [88] One of the coupling partners( 119)w as synthesized from methyl (S)-(+ +)-3-hydroxylbutyrate (116) by diastereoselectivea lkylation of lithium enolate (98:2 diastereoselectivity), followed by silyl protection, DIBAL reduction,S wern oxidation, [89] and Ohira-Bestmann homologation. [90] The Pd-catalyzed CÀCb ond formation [91] underwent smoothly,a nd the cationic Au I -catalyzed cycloisomerization of the compound 121 yielded the desired cyclopentene (123), presumably throught he generation of Au-carbene com-Scheme18.…”

Section: Limonenea Nalogsmentioning

confidence: 99%

Synthetic Strategies for (−)‐Cannabidiol and Its Structural Analogs

Jung

Lee

Jungnam

et al. 2019

Chemistry An Asian Journal

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À)-Cannabidiol ((À)-CBD), an on-psychoactive phytocannabinoid from Cannabis,a nd its structural analogs have received growinga ttention in recent years because of their potentialt herapeutic benefits, including neuroprotective, anti-epileptic,a nti-inflammatory,a nxiolytic, and anticancer properties. (À)-CBD and its analogs have been obtained mainly based on extraction from the natural source; however,t he conventional extraction-based methods have some drawbacks, such as poor quality controla long with purification difficulty.C hemical-synthetic strategies for (À)-CBD could tackle these issues, and, additionally,g enerate novel (À)-CBD analogs that exhibit advanced biological activities. This review concisely summarizes the historic and recent milestones in the synthetic strategies for (À)-CBD and its analogs.

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“…The terpenoid structure of cannabimovone replaces the cyclohexenyl ring of CBD by a functionalized cyclopentane including four contiguous stereocenters. Its total synthesis has been reported very recently (Carreras et al, 2016). Cannabimovone is devoid of CB 1 and CB 2 activity, whereas it is a weak TPRV1 agonist.…”

Section: Synthetic Cbd Analogsmentioning

confidence: 99%

An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol

2017

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Cannabidiol (CBD) has been traditionally used in Cannabis-based preparation, however historically, it has received far less interest as a single drug than the other components of Cannabis. Currently, CBD generates considerable interest due to its beneficial neuroprotective, antiepileptic, anxiolytic, antipsychotic, and anti-inflammatory properties. Therefore, the CBD scaffold becomes of increasing interest for medicinal chemists. This review provides an overview of the chemical structure of natural and synthetic CBD derivatives including the molecular targets associated with these compounds. A clear identification of their biological targets has been shown to be still very challenging.

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Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

Abstract: The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of a highly stereoselective gold(I)‐catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone.

Cited by 30 publications

References 59 publications

Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

Synthetic Strategies for (−)‐Cannabidiol and Its Structural Analogs

An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol

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