Methods of making precursor compounds for making cannabinoids and / or methods of making cannabinoids

Abstract

The present disclosure relates to methods of manufacturing cannabinoids (including cannabinoid precursors) and / or derivatives thereof.

Description

Technical Field

[0001] Generally, this disclosure relates to the manufacture of cannabinoids and / or cannabinoid precursors. Specifically, this disclosure relates to the use of cashew nutshell liquid (CNSL) and / or its chemical components in methods for manufacturing cannabinoids and / or cannabinoid precursors. In some embodiments, this disclosure relates to the use of cashew nutshell extract and / or cashew nutshell diol and / or aromatic hydrocarbons and / or symmetrical resorcinol in the manufacture of cannabinoids and / or cannabinoid precursors. In some other exemplary embodiments, this disclosure relates to the use of cashew nutshell extract and / or cashew nutshell diol and / or aromatic hydrocarbons and / or symmetrical resorcinol in the manufacture of cannabinoids and / or cannabinoid precursors, wherein at least one of cashew nutshell extract and / or cashew nutshell diol and / or aromatic hydrocarbons and / or symmetrical resorcinol is derived from CNSL. This disclosure extends to cannabinoids and / or cannabinoid precursors themselves. Specifically, this disclosure extends to cannabinoids and / or cannabinoid precursors manufactured according to the methods described herein. Background Technology

[0002] In recent years, there has been a trend towards abandoning petroleum or petroleum-based products as starting agents in the organic synthesis of commercially relevant chemicals. To utilize sustainable carbon sources as starting agents in organic synthesis, researchers have considered using biomass, particularly inedible biomass that would otherwise be discarded. Thus, the high-value utilization of inedible biomass and / or waste biomass has been a subject of considerable research.

[0003] Cashew nut shell liquid (CNSL) is one inedible biomass source that has been extensively studied. While CNSL itself is known to have low commercial value, it is rich in phenolic compounds and is known as a source of inedible biomass-derived chemicals used in the production of coatings, resins, polymers, and surfactants. Cashews are a common, high-value crop in many developing countries, and the high-value utilization of any waste products generated from their cultivation could provide much-needed economic benefits and / or improve livelihoods in these countries.

[0004] In addition, consumers have become increasingly reluctant to purchase products derived from unsustainable sources.

[0005] CNSL typically comprises a mixture of phenolic compounds. The main components of a CNSL include three structure-associated cashew acids and three structure-associated cashew phenols, as well as trace amounts of three structure-associated cashew diols. Cashew diols are present in trace amounts in CNSLs, but they are compounds that can be used as molecular building blocks for the production of higher-value chemicals via appropriate downstream organic synthesis.

[0006] Because the three structurally related cashew glycosides are present in trace amounts in CNSL, obtaining sufficient quantities for downstream processing into higher-value compounds is difficult and costly. Known alternative synthetic routes for producing cashew glycosides are also costly and time-consuming. The current market price for cashew glycosides is approximately $660 / 10g, which is considered excessive, thus limiting its use and application in the production of higher-value downstream compounds.

[0007] Over the past decade, research into the manufacture and use of cannabinoids has increased as more and more jurisdictions worldwide have legalized and continued to legalize cannabis. In humans or animals, cannabinoids target cannabinoid receptors CB and CB2 as part of their biochemical and / or physiological mechanisms of action. In the medical field, cannabinoids are known for their use in treating and / or preventing and / or improving nausea, pain, and / or cramps. Two known FDA-approved drugs derived from cannabinoids are Marinol® and Syndros®. Both Marinol® and Syndros® contain synthetic 9-tetrahydrocannabinol (THC), also known as dronabinol. Another drug, Cesamet®, contains cannabinol, which is derived from tetrahydrocannabinol (THCP). Both dronabinol and cannabinol are used to treat nausea and vomiting caused by cancer chemotherapy.

[0008] The most well-known cannabinoids are those found in the cannabis plant, leading to an increase in both home and commercial cultivation of this crop. There have been reports of negative environmental impacts from cannabis cultivation, as well as safety concerns surrounding the use, harvesting, and disposal of waste products containing phytochemicals that may impair and / or affect motor function and / or cognitive abilities. Unregulated disposal of potentially hazardous waste, including biomass waste from cannabis plants, poses public safety concerns. Furthermore, plant material is not used as a source of tetrahydrocannabinol (THC) for pharmaceutical applications because isolating it from over 100 other cannabinoids is extremely difficult; thus, in pharmaceutical applications, THC is typically synthesized from synthetic oleuropein.

[0009] There is a need to mitigate the negative environmental and safety impacts of cannabis cultivation. There is a need to provide a method for producing cannabinoids (including their precursors) from inedible biomass sources, wherein such biomass may also be waste products, and wherein the waste products themselves do not contain chemical substances at concentrations sufficiently high to elicit motor and / or cognitive responses in humans or animals upon ingestion. There is a need to address at least one of the disadvantages described above or otherwise known in the prior art. Summary of the Invention

[0010] Generally, this disclosure relates to methods for manufacturing cannabinoids (including cannabinoid precursors) and / or their derivatives.

[0011] In a broad sense, any one or more of the methods described herein can provide, in some embodiments, a method for the high-value utilization of cashew nut shell liquid (CNSL) and / or its chemical components.

[0012] In a broad sense, this method, in certain embodiments, each includes the use of cashew nut shell liquid (CNSL) and / or its chemical components as a source of raw materials. In embodiments where the chemical components of CNSL are utilized, it should be understood that such chemical components are directly derived from CNSL. Alternatively and / or additionally, it should be understood that such chemical components may be synthetically derived. Alternatively and / or additionally, it should be understood that such chemical components may be obtained from sources different from CNSL. Cashew nut shell liquid (CNSL) and / or its chemical components may include cashew acid and / or cashew phenol and / or cashew diol and / or aromatic hydrocarbons and / or symmetrical resorcinol.

[0013] According to a first aspect of this disclosure, a method for manufacturing cannabinoids and / or cannabinoid precursors and / or derivatives thereof is provided. This method may include the use of cashew acid and / or cashew phenol and / or cashew diol. In some example embodiments, at least one of cashew acid and / or cashew phenol and / or cashew diol is derived from CNSL and / or its chemical components. This disclosure extends to cannabinoids and / or cannabinoid precursors themselves. Specifically, this disclosure extends to cannabinoids and / or cannabinoid precursors manufactured according to the methods described herein.

[0014] Precursor compounds used to manufacture cannabinoids may include cashew-derived phenolic compounds.

[0015] The precursor compound may include, but is not limited to, 5-pentylresorcinol (olyl alcohol) and / or 5-heptylresorcinol (spherophorol), which can be used, respectively, for the downstream processing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabinoheptol (THCP).

[0016] According to a second aspect of this disclosure, a method is provided for producing cannabinoids and / or cannabinoid precursors and / or derivatives thereof from cashew nut shell liquid (CNSL), wherein the CNSL comprises cashew acid, cashew phenol, and cashew diol, the method comprising the following steps: (a) Decarboxylating cashew acid to provide for the synthesis of cashew phenol; (b) Protection of cashew nut bicarbonate and synthetic cashew nut phenol, providing protected cashew nut bicarbonate and protected cashew nut phenol, including protection by providing acetylated cashew nut bicarbonate and acetylated cashew nut phenol through acetylation of cashew nut bicarbonate and synthetic cashew nut phenol; (c) Cleavage of the olefinic bonds of acetylated cashew nut biphenol and acetylated cashew phenol, wherein cleavage provides CNSL aldehyde, including in one embodiment ozone decomposition of acetylated cashew nut biphenol and acetylated cashew phenol to provide CNSL aldehyde; (d) Defunctionalizing CNSL aldehydes, including decarbonylating CNSL aldehydes to provide saturated and / or unsaturated alkylated CNSL hydrocarbons.

[0017] Step (b) may include protection using at least one of the following protective functional groups (but not limited to): methanesulfonate, toluenesulfonate, and acetal. Step (b) may be optional.

[0018] Step (c) may include olefin cleavage via at least one (but not limited to) oxidizing and / or non-oxidizing olefin cleavage from the group consisting of: dihydroxylation, RuCl3-mediated methods, Oxone-mediated methods, periodate-mediated methods, and Grubbs olefin metathesis.

[0019] Step (d) can occur via at least two different synthetic pathways, namely steps (d1) and (d2). The method according to this disclosure may employ both steps (d1) and (d2). Alternatively, the method according to this disclosure may employ only one of steps (d1) or (d2).

[0020] Step (d1) involves reacting the CNSL aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene. Typically, step (d1) occurs between 80°C and 100°C and lasts between 10 minutes and 24 hours. Preferred example embodiments of this step are shown below.

[0021] Step (d1) provides unsaturated alkylated CNSL hydrocarbons. Typically, these unsaturated alkylated CNSL hydrocarbons are olefins.

[0022] The applicant has envisioned additional and / or alternative synthetic strategies, including but not limited to contacting / reacting / exposing CNSL-derived / CNSL-based alcohols, aldehydes and / or carboxylic acids with / to palladium and / or iridium catalysts.

[0023] In addition, the applicant provides another synthetic strategy, which includes functional group interconversion into leaving groups, base-mediated E2 elimination to obtain alkenes, and cleavage of alkenes.

[0024] In addition, the applicant provides another synthetic strategy, which involves the direct dehydration of aldehyde-derived hydroxyl groups using acids (including but not limited to p-toluenesulfonic acid and / or propanephosphonic anhydride).

[0025] Furthermore, the applicant provides an alternative synthetic strategy comprising condensing CNSL aldehyde with malonic acid under basic conditions to carry out decarboxylation and olefin isomerization therein, thereby providing a precursor compound according to this disclosure.

[0026] Step (d) can be optional.

[0027] Furthermore, the unsaturated alkylated CNSL hydrocarbon is an olefin and can be further hydrogenated to provide a saturated alkylated CNSL hydrocarbon. It should be understood that further downstream processing is provided. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0028] Furthermore, the unsaturated alkylated CNSL hydrocarbon is an olefin and can be further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length. It should be understood that further downstream processing is contemplated. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0029] Step (d2) involves reacting the CNSL aldehyde with [Ir(COD)₂Cl]₂, PPh₃, and 2MeTHF. Typically, step (d2) occurs between 80°C and 150°C and lasts between 10 and 180 minutes. Preferred example embodiments of this step are shown below. Step (d2) may alternatively and / or additionally include exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The applicant provides for further carbon-carbon cracking reactions, preferably metal-catalyzed, of any CNSL-derived / CNSL-based alcohols, aldehydes, and / or carboxylic acids to provide saturated straight-chain alkanes.

[0030] Step (d2) provides saturated alkylated CNSL hydrocarbons.

[0031] The cannabinoid precursors and / or derivatives provided according to this method may include 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

[0032] The precursor compounds 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol can be used, respectively, for the downstream processing of cannabinoids, including tetrahydrocannabinol (THC) and tetrahydrocannabinone (THCP).

[0033] It should be understood that further downstream processing is provided. The applicant provides non-limiting example implementations of such further downstream processing below.

[0034] According to a third aspect of this disclosure, a method for manufacturing cannabinoids and / or cannabinoid precursors and / or derivatives thereof is provided, the method comprising the following steps: (a) Protecting cashew nut bicarbonate and / or cashew phenol, providing protected cashew nut bicarbonate and / or protected cashew phenol, including by providing acetylated cashew nut bicarbonate and / or acetylated cashew phenol through acetylation of cashew nut bicarbonate and / or cashew phenol; (b) Cleavage of the olefinic bonds of acetylated cashew nut biphenol and / or acetylated cashew nut alcohol, wherein cleavage provides an aldehyde, including in one embodiment ozone decomposition of acetylated cashew nut biphenol and / or acetylated cashew nut alcohol to provide an aldehyde; (c) Defunctionalizing aldehydes, including decarbonylating aldehydes to provide saturated and / or unsaturated alkylated hydrocarbons.

[0035] In this method, at least one of cashew nut biphenol and / or cashew phenol is derived from cashew nut shell liquid (CNSL).

[0036] Step (a) may include protection using at least one of the following protective functional groups (but not limited to): methanesulfonate, toluenesulfonate, and acetal. Step (b) may be optional.

[0037] Step (c) may include olefin cleavage via at least one (but not limited to) oxidizing and / or non-oxidizing olefin cleavage from the group consisting of: dihydroxylation, RuCl3-mediated methods, Oxone-mediated methods, periodate-mediated methods, and Grubbs olefin metathesis.

[0038] Step (c) can occur via at least two different synthetic pathways, namely steps (c1) and (c2). The method according to this disclosure may employ both steps (c1) and (c2). Alternatively, the method according to this disclosure may employ only one of steps (c1) or (c2).

[0039] Step (c1) involves reacting the aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene. Typically, step (c1) occurs between 80°C and 100°C and lasts between 10 minutes and 24 hours. Preferred example embodiments of this step are shown below.

[0040] Step (c1) provides an unsaturated alkylated hydrocarbon. Typically, the unsaturated alkylated hydrocarbon is an olefin.

[0041] The applicant has provided additional and / or alternative synthetic strategies, including but not limited to contacting / reacting / exposing CNSL-derived / CNSL-based alcohols, aldehydes and / or carboxylic acids to palladium and / or iridium catalysts.

[0042] In addition, the applicant provides another synthetic strategy, which includes functional group interconversion into leaving groups, base-mediated E2 elimination to obtain alkenes, and cleavage of alkenes.

[0043] In addition, the applicant provides another synthetic strategy, which involves the direct dehydration of aldehyde-derived hydroxyl groups using acids (including but not limited to p-toluenesulfonic acid and / or propanephosphonic anhydride).

[0044] Furthermore, the applicant provides an alternative synthetic strategy comprising condensing CNSL aldehyde with malonic acid under basic conditions to carry out decarboxylation and olefin isomerization therein, thereby providing a precursor compound according to this disclosure.

[0045] Step (c) is optional.

[0046] Furthermore, the unsaturated alkylated hydrocarbon is an olefin and can be further hydrogenated to provide a saturated alkylated hydrocarbon. It should be understood that further downstream processing is contemplated. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0047] Furthermore, the unsaturated alkylated hydrocarbon is an olefin and can be further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length. It should be understood that further downstream processing is envisioned. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0048] Step (c2) involves reacting the aldehyde with [Ir(COD)₂Cl]₂, PPh₃, and 2MeTHF. Typically, step (c2) occurs between 80°C and 150°C and lasts between 10 and 180 minutes. Preferred example embodiments of this step are shown below. Step (c2) may alternatively and / or additionally include exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The applicant envisions further carbon-carbon cracking reactions, preferably metal-catalyzed, of CNSL-derived / CNSL-based alcohols, aldehydes, and / or carboxylic acids to provide saturated straight-chain alkanes.

[0049] Step (c2) provides saturated alkylated hydrocarbons.

[0050] The cannabinoid precursors and / or derivatives provided according to this method may include 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

[0051] The precursor compounds 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol can be used, respectively, for the downstream processing of cannabinoids, including tetrahydrocannabinol (THC) and tetrahydrocannabinone (THCP).

[0052] It should be understood that further downstream processing is envisioned. The applicant provides non-limiting example implementations of such further downstream processing below.

[0053] According to the fourth aspect of this disclosure, the use of cannabinoids and / or cannabinoid precursors and / or their derivatives manufactured according to the first to third aspects in the manufacture of medicaments for treating, preventing and / or improving diseases and / or medical conditions is provided.

[0054] According to the fifth aspect of this disclosure, cannabinoids and / or cannabinoid precursors and / or derivatives thereof manufactured according to the first to third aspects are provided for use as a medicine for treating, preventing and / or improving diseases and / or medical conditions.

[0055] According to a sixth aspect of this disclosure, a method is provided for treating, preventing, and / or improving diseases and / or medical conditions using cannabinoids and / or cannabinoid precursors and / or derivatives manufactured according to the methods described herein.

[0056] The following text provides non-limiting examples of cannabinoids and / or their derivatives and methods of production thereof, which are incorporated herein by reference to avoid duplication. Further examples are provided herein. Figures 1 to 9 Any one or more of the methods.

[0057] Further provided are any of the first to sixth aspects of this disclosure, which are substantially as described, illustrated and / or illustrated herein with reference to any of the descriptions and / or examples and / or photographs and / or images and / or reaction schemes and / or diagrams herein. Attached Figure Description

[0058] The embodiments of this disclosure will be described below by way of example only and with reference to the accompanying drawings, photographs and / or chemical reaction schemes, and the drawings should not be construed as limiting the scope of this disclosure or any part thereof.

[0059] Figure 1 The reaction scheme is shown as a method for the high-value utilization of cashew nut shell liquid (CNSL) according to the present disclosure.

[0060] Figure 2 The acetylation of cashew nut shell liquid (CNSL) is shown.

[0061] Figure 3 This illustrates the ozone decomposition of acetylated CNSL.

[0062] Figure 4 This illustrates the ozone decomposition of terminally unsaturated CNSL.

[0063] Figure 5 The CNSL heptyloctyl aldehyde is shown to be decarbonylated into a saturated alkane.

[0064] Figure 6 The CNSL pentylhexyl aldehyde is shown to be decarbonylated into a saturated alkane.

[0065] Figure 7 The reverse hydroformylation reaction of an aldehyde mixture is shown.

[0066] Figure 8 One-pot molecular homogenization is shown to provide 5-heptylphenyl-1,3-diol.

[0067] Figure 9 One-pot molecular homogenization is shown to provide 5-pentylphenyl-1,3-diol. Detailed Implementation

[0068] The general provisions of the invention are incorporated herein by reference and, to avoid repetition, will not be repeated in their entirety. The detailed description and examples below include specific embodiments of this disclosure and should not be construed as limiting in any way. Several alternatives will be conceived by those skilled in the art without departing from the scope of this disclosure.

[0069] Cashew nut shell liquid (CNSL) has been identified as a sustainably produced biomass and chemical feedstock. Compared to prior art methods that provide the same or similar compounds (e.g., cashew nutmeg and / or its derivatives, cashew nutmeg and / or its derivatives, and cannabinoids (including precursors) and their derivatives), the methods of this disclosure and the use of CNSL in chemicals and / or compositions produced by employing this method are highly cost-effective and provide a simplified organic synthesis route, thereby significantly reducing the number of process steps, solvents used, energy consumption, and time. The applicant believes that the methods according to this disclosure provide a technical solution to technical problems existing in the prior art. Furthermore, there are no hints and / or suggestions in the prior art that would lead a person skilled in the art to regard CNSL as a raw material or starting agent required for the production of the chemicals and / or compositions of this disclosure.

[0070] The main phenolic components of CNSL include, but are not limited to, cashew acid, cashew phenol, and 5-alkylresorcinol (including cashew nut glycol), with cashew acid and cashew phenol being the major phenolic components and 5-alkylresorcinol (including cashew nut glycol) being a trace component. Typically, cashew nut glycol and cashew phenol can be used as molecular building blocks in downstream processes to provide high-value chemical compounds.

[0071] Phenolic compounds (cashew acid, cashew phenol, and cashew diol) were extracted and isolated from CNSL using known organic separation methods for use in further downstream processing, synthesis, functionalization, and / or transformation and / or synthetic procedures as described herein.

[0072] This disclosure relates to the use of CNSL and / or its chemical components in methods for manufacturing cannabinoids and / or their derivatives (including precursors). This extends to the use of such manufactured cannabinoids in the manufacture of medicines for treating diseases and / or medical conditions. The methods disclosed below and the example embodiments of the resulting cannabinoids should not be considered limiting. Using CNSL as a source of raw materials avoids the environmental and safety issues associated with cannabis crop cultivation and the disposal of related waste products.

[0073] According to a first aspect of this disclosure, a method for manufacturing a precursor compound for producing cannabinoids and / or a method for producing cannabinoids is provided. In some embodiments, the method includes using CNSL and / or its chemical components, wherein the CNSL may contain cashew acid, cashew phenol, cashew diol, and / or aromatic hydrocarbons and / or symmetrical resorcinol. This disclosure extends to the precursor compound and / or cannabinoids themselves.

[0074] Precursor compounds used to manufacture cannabinoids may include cashew-derived phenolic compounds.

[0075] The cannabinoids and / or cannabinoid precursors and / or their derivatives provided according to this method may include 5-heptaylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

[0076] Typically, the precursor compound may include, but is not limited to, 5-pentylresorcinol and / or 5-heptylresorcinol, which can be used, respectively, for the downstream processing of cannabinoids, including tetrahydrocannabinol (THC) and tetrahydrocannabinone (THCP).

[0077] According to a second aspect of this disclosure, a method is provided for producing cannabinoids and / or their derivatives from cashew nut shell liquid (CNSL), the CNSL comprising cashew acid, cashew phenol, and cashew diol, the method comprising the following steps: (a) Decarboxylating cashew acid to provide for the synthesis of cashew phenol; (b) Protection of cashew nut bicarbonate and synthetic cashew nut phenol, providing protected cashew nut bicarbonate and protected cashew nut phenol, including protection by providing acetylated cashew nut bicarbonate and acetylated cashew nut phenol through acetylation of cashew nut bicarbonate and synthetic cashew nut phenol; (c) Cleavage of the olefinic bonds of acetylated cashew nut biphenol and acetylated cashew phenol, wherein cleavage provides CNSL aldehyde, including in one embodiment ozone decomposition of acetylated cashew nut biphenol and acetylated cashew phenol to provide CNSL aldehyde; (d) Defunctionalizing CNSL aldehydes, including decarbonylating CNSL aldehydes to provide saturated or unsaturated alkylated CNSL hydrocarbons.

[0078] Step (b) may include protection using at least one of the following protective functional groups (but not limited to): methanesulfonate, toluenesulfonate, and acetal. Step (b) may be optional.

[0079] Step (c) may include olefin cleavage via at least one (but not limited to) oxidizing and / or non-oxidizing olefin cleavage from the group consisting of: dihydroxylation, RuCl3-mediated methods, Oxone-mediated methods, periodate-mediated methods, and Grubbs olefin metathesis.

[0080] Step (d) can occur via at least two different synthetic pathways, namely steps (d1) and (d2). The method according to this disclosure may employ both steps (d1) and (d2). Alternatively, the method according to this disclosure may employ only one of steps (d1) or (d2).

[0081] Step (d1) involves reacting the CNSL aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene. Typically, step (d1) occurs between 80°C and 100°C and lasts between 10 minutes and 24 hours. Preferred example embodiments of this step are shown below.

[0082] Step (d1) provides unsaturated alkylated CNSL hydrocarbons. Typically, these unsaturated alkylated CNSL hydrocarbons are olefins.

[0083] The applicant has envisioned additional and / or alternative synthetic strategies, including but not limited to contacting / reacting / exposing CNSL-derived / CNSL-based alcohols, aldehydes and / or carboxylic acids with / to palladium and / or iridium catalysts.

[0084] In addition, the applicant envisions another synthetic strategy, including functional group interconversion into leaving groups, base-mediated E2 elimination to obtain alkenes, and cleavage of alkenes.

[0085] In addition, the applicant envisions another synthetic strategy involving the direct dehydration of aldehyde-derived hydroxyl groups using acids (including but not limited to p-toluenesulfonic acid and / or propanephosphonic anhydride).

[0086] Furthermore, the applicant envisions another synthetic strategy involving the condensation of CNSL aldehyde with malonic acid under basic conditions to carry out decarboxylation and olefin isomerization therein, thereby providing a precursor compound according to this disclosure.

[0087] Step (d) can be optional.

[0088] Furthermore, the unsaturated alkylated CNSL hydrocarbon is an olefin and can be further hydrogenated to provide a saturated alkylated CNSL hydrocarbon. It should be understood that further downstream processing is contemplated. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0089] Furthermore, the unsaturated alkylated CNSL hydrocarbon is an olefin and can be further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length. It should be understood that further downstream processing is contemplated. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0090] Step (d2) involves reacting the CNSL aldehyde with [Ir(COD)₂Cl]₂, PPh₃, and 2MeTHF. Typically, step (d2) occurs between 80°C and 150°C and lasts between 10 and 180 minutes. Preferred example embodiments of this step are shown below. Step (d2) may alternatively and / or additionally include exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The applicant envisions further carbon-carbon cracking reactions, preferably metal-catalyzed, of CNSL-derived / CNSL-based alcohols, aldehydes, and / or carboxylic acids to provide saturated straight-chain alkanes.

[0091] Step (d2) provides saturated alkylated CNSL hydrocarbons.

[0092] The cannabinoids and / or cannabinoid precursors and / or their derivatives provided according to this method may include 5-heptaylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

[0093] Typically, the precursor compound may include, but is not limited to, 5-pentylresorcinol and / or 5-heptylresorcinol, which can be used, respectively, for the downstream processing of cannabinoids, including tetrahydrocannabinol (THC) and tetrahydrocannabinone (THCP).

[0094] It should be understood that further downstream processing is envisioned. The applicant provides non-limiting example implementations of such further downstream processing below.

[0095] According to a third aspect of this disclosure, a method for manufacturing cannabinoids and / or their derivatives is provided, the method comprising the following steps: (a) Protecting cashew nut bicarbonate and / or cashew phenol, providing protected cashew nut bicarbonate and / or protected cashew phenol, including by providing acetylated cashew nut bicarbonate and acetylated cashew phenol through acetylation of cashew nut bicarbonate and / or cashew phenol; (b) Cleavage of the olefinic bonds of acetylated cashew nut biphenol and / or acetylated cashew nut alcohol, wherein cleavage provides an aldehyde, including in one embodiment ozone decomposition of acetylated cashew nut biphenol and / or acetylated cashew nut alcohol to provide an aldehyde; (c) Defunctionalizing aldehydes, including decarbonylating aldehydes to provide saturated or unsaturated alkylated hydrocarbons.

[0096] In this method, at least one of cashew nut biphenol and / or cashew phenol is derived from cashew nut shell liquid (CNSL).

[0097] Step (a) may include protection using at least one of the following protective functional groups (but not limited to): methanesulfonate, toluenesulfonate, and acetal. Step (b) may be optional.

[0098] Step (c) may include olefin cleavage via at least one (but not limited to) oxidizing and / or non-oxidizing olefin cleavage from the group consisting of: dihydroxylation, RuCl3-mediated methods, Oxone-mediated methods, periodate-mediated methods, and Grubbs olefin metathesis.

[0099] Step (c) can occur via at least two different synthetic pathways, namely steps (c1) and (c2). The method according to this disclosure may employ both steps (c1) and (c2). Alternatively, the method according to this disclosure may employ only one of steps (c1) or (c2).

[0100] Step (c1) involves reacting the aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene. Typically, step (c1) occurs between 80°C and 100°C and lasts between 10 minutes and 24 hours. Preferred example embodiments of this step are shown below.

[0101] Step (c1) provides an unsaturated alkylated hydrocarbon. Typically, the unsaturated alkylated hydrocarbon is an olefin.

[0102] The applicant has envisioned additional and / or alternative synthetic strategies, including but not limited to contacting / reacting / exposing CNSL-derived / CNSL-based alcohols, aldehydes and / or carboxylic acids with / to palladium and / or iridium catalysts.

[0103] In addition, the applicant envisions another synthetic strategy, including functional group interconversion into leaving groups, base-mediated E2 elimination to obtain alkenes, and cleavage of alkenes.

[0104] In addition, the applicant envisions another synthetic strategy involving the direct dehydration of aldehyde-derived hydroxyl groups using acids (including but not limited to p-toluenesulfonic acid and / or propanephosphonic anhydride).

[0105] Furthermore, the applicant envisions another synthetic strategy involving the condensation of CNSL aldehyde with malonic acid under basic conditions to carry out decarboxylation and olefin isomerization therein, thereby providing a precursor compound according to this disclosure.

[0106] Step (c) is optional.

[0107] Furthermore, the unsaturated alkylated hydrocarbon is an olefin and can be further hydrogenated to provide a saturated alkylated hydrocarbon. It should be understood that further downstream processing is contemplated. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0108] Furthermore, the unsaturated alkylated hydrocarbon is an olefin and can be further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length. It should be understood that further downstream processing is envisioned. The applicant provides non-limiting example embodiments of such further downstream processing below.

[0109] Step (c2) involves reacting the aldehyde with [Ir(COD)₂Cl]₂, PPh₃, and 2MeTHF. Typically, step (c2) occurs between 80°C and 150°C and lasts between 10 and 180 minutes. Preferred example embodiments of this step are shown below. Step (c2) may alternatively and / or additionally include exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The applicant envisions further carbon-carbon cracking reactions, preferably metal-catalyzed, of CNSL-derived / CNSL-based alcohols, aldehydes, and / or carboxylic acids to provide saturated straight-chain alkanes.

[0110] Step (c2) provides saturated alkylated hydrocarbons.

[0111] The cannabinoids and / or cannabinoid precursors and / or their derivatives provided according to this method may include 5-heptaylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

[0112] Typically, the precursor compound may include, but is not limited to, 5-pentylresorcinol and / or 5-heptylresorcinol, which can be used, respectively, for the downstream processing of cannabinoids, including tetrahydrocannabinol (THC) and tetrahydrocannabinone (THCP).

[0113] It should be understood that further downstream processing is envisioned. The applicant provides non-limiting example implementations of such further downstream processing below.

[0114] Non-limiting embodiments: Vacuum distillation of crude industrial grade CNSL: Crude industrial-grade cashew nut shell liquid (approximately 100 g) obtained from cashew nut shell waste by Soxhlet extraction or mechanical pressing is vacuum distilled at 180°C to 200°C (approximately 10 mmHg) while simultaneously decarboxylating cashew acid to provide CNSL (82 g) containing cashew phenol (approximately 90%) and cashew diol (approximately 10%).

[0115] Figure 1 A reaction scheme for obtaining cashew nut shell liquid (CNSL) and cashew diol is shown.

[0116] Acetylation of CNSL: Method A: Under an inert argon atmosphere, pentovalin (13.00 g, 69.8 mmol) was added to a 50 mL sealed tube containing a distilled CNSL mixture (20.00 g, approximately 63.1 mmol), followed by the addition of triethylamine (10.12 g, 100 mmol). The resulting solution was stirred and heated to 100-110 °C for 2 hours, after which TLC (thin-layer chromatography) analysis confirmed the completion of the reaction. The reaction mixture was then poured into 200 mL of saturated NaHCO3 aqueous solution and stirred at room temperature for 30 minutes. The resulting biphasic mixture was then extracted into n-hexane (3 × 100 mL), and the combined organic extracts were washed sequentially with saturated NaHCO3 solution (100 mL), water (100 mL), and then with 1 M HCl aqueous solution (100 mL). The organic phase was then dried with MgSO4 and volatiles were removed under vacuum to provide a mixture of acetylated products (25.6 g, about 63 mmol, quantified) as a pale yellow oil.

[0117] Figure 2 The acetylation of CNSL as described above is shown.

[0118] Ozone decomposition reaction

[0119] Ozone decomposition of acetylated CNSL mixtures: Distilled water (30 mL) was added to a solution of acetylated CNSL mixture (12.31 g, approximately 30.9 mmol) in acetone (300 mL). The solution was cooled in an ice bath while ozone gas was bubbled through it for 40 minutes until the reaction was confirmed to be complete by TLC. Oxygen was then bubbled through the reaction solution for 2 minutes, followed by argon for 5 minutes to degas the reaction solution. The solution was then stirred while maintaining the ice bath cooling, and dimethyl sulfide (20 mL, 16.8 g, 0.27 mol) was added via syringe. The mixture was stirred overnight at room temperature. After this time, NMR analysis showed residual secondary ozonides (characteristic multiplets at 5.3 ppm to 5.19 ppm). Therefore, the solution was heated under reflux (bath temperature 60 °C) for 3 hours until the reaction was confirmed to be complete by NMR analysis. The solvent was removed under vacuum until a two-phase mixture of the remaining product and residual water was obtained. Heptane (100 mL) was added, followed by saturated NaHCO3 solution (100 mL). 1 The phases were shaken and separated. The aqueous phase was re-extracted with heptane (2 × 50 mL), and the organic matter was combined and again extracted with saturated NaHCO3 solution (100 mL). 1 Washed, then washed with water (100 mL). The combined extracts were dried over MgSO4 and volatiles were removed under vacuum to provide a mixture of aldehydes (10.10 g, 32.2 mmol, approximately 104% yield). 2 It is a colorless, oily substance with a distinctive nutty aroma. This material is used without further purification.

[0120] 1 Note: A small amount of salt water is needed during the initial wash to break the emulsion.

[0121] 2 Note: The material contains residual non-volatile heptaldehyde and malondialdehyde as byproducts.

[0122] 1 H NMR (400 MHz, CDCl3) δ 9.79 – 9.69 (m, 1H), 7.29 – 7.22 (m, 1H), 7.08 – 6.96 (m, 1H), 6.90 – 6.82 (m, 2H), 6.77 – 6.61 (m, 0H), 2.64 – 2.53(m, 2H), 2.49 – 2.35 (m, 2H), 1.65 – 1.57 (m, 4H), 1.38 – 1.34 (m, 9H), 1.34– 1.29 (m, 6H).

[0123] 13C NMR (101 MHz, CDCl3) δ 202.93, 202.85, 177.12, 151.33, 151.08,145.07, 144.47, 144.39, 129.04, 129.00, 125.65, 121.33, 118.65, 118.58,112.55, 77.40, 77.27, 77.08, 76.75, 43.91, 43.87, 39.09, 39.04, 35.78, 35.70,31.93, 31.54, 31.29, 31.15, 30.92, 29.67, 29.58, 29.49, 29.37, 29.31, 29.17, 29.13, 29.04, 29.03, 28.83, 27.32, 27.16, 27.11, 26.51, 22.70, 22.46, 22.04, 22.03, 14.13, 14.01.

[0124] exist Figure 3 The ozone decomposition of acetylated CNSL is shown in the figure.

[0125] Ozone decomposition of terminally unsaturated CNSL mixtures: Distilled water (10 mL) was added to a 100 mL solution of a terminally unsaturated CNSL mixture (0.710 g, approximately 2.50 mmol) (see reaction below for preparation of starting materials). The solution was cooled in an ice bath while ozone gas was bubbled through it for 20 minutes until the reaction was confirmed to be complete by TLC. Oxygen was then bubbled through the reaction solution for 2 minutes, followed by argon for 5 minutes to degas the reaction solution. The solution was then stirred while maintaining the ice bath cooling, and dimethyl sulfide (10 mL, 8.40 g, 0.14 mol) was added via syringe. The mixture was stirred overnight at room temperature. After this time, NMR analysis showed residual secondary ozonides (characteristic multiplets at 5.3 ppm to 5.19 ppm). Therefore, the solution was refluxed (bath temperature 60 °C) for 3 hours until the reaction was confirmed to be complete by NMR analysis. The solvent was removed under vacuum until a two-phase mixture of the remaining product and residual water was obtained. Add heptane (100 mL), followed by saturated NaHCO3 solution (100 mL)¹, and shake and separate the phases. Re-extract the aqueous phase with heptane (2 × 50 mL), and combine the organic matter, again with saturated NaHCO3 solution (100 mL). 1The extract was washed, followed by washing with water (100 mL). The combined extracts were dried over MgSO4 and volatiles were removed under vacuum to provide a mixture of aldehydes (0.697 g, 2.43 mmol, approximately 97% yield) as a colorless oil. This material was used without further purification.

[0126] Figure 4 This illustrates the ozone decomposition of terminally unsaturated CNSL.

[0127] 1 H NMR (300 MHz, CDCl3) δ 9.75 (t, J = 1.7 Hz, 1H), 7.31 – 7.22 (m,1H), 7.02 (d, J = 7.7 Hz, 1H), 6.87 (d, J = 6.0 Hz, 2H), 6.78 – 6.65 (m, 0H), 2.69 – 2.54 (m, 2H), 2.42 (td, J = 1.6, 7.3 Hz, 2H), 1.72 – 1.57 (m, 5H), 1.35 (s, 9H), 1.34 – 1.32 (m, 2H).

[0128] 13 C NMR (75 MHz, CDCl3) δ 202.65, 177.12, 151.11, 144.01, 129.11,125.63, 121.34, 118.77, 118.64, 43.78, 39.05, 35.46, 30.93, 28.71, 27.15,27.11, 21.87.

[0129] CNSL aldehydes undergo carbonylation to form saturated alkanes: Heptyline mixture: Heptane (10 mL) was added to a crude CNSL aldehyde mixture (1.22 g, approximately 3.88 mmol), and the solution was stirred under an argon atmosphere for 5 minutes. Palladium on carbon (10 wt%, 0.212 g, 0.2 mmol, 5 mol%) was then added, and the reaction mixture was heated under reflux for 24 hours, at which point ¹H NMR analysis indicated the reaction was complete. After cooling to room temperature, ethanol (20 mL) was added, and the reaction mixture was hydrogenated at room temperature under a hydrogen atmosphere (1 atm) for 16 hours. The reaction mixture was then filtered through diatomaceous earth, washed with ethanol (3 × 20 mL), and the combined filtrates were solvent-removed under vacuum to provide the crude product. The crude product was dissolved in heptane (50 mL), washed with a saturated aqueous solution of NaHCO3 (50 mL), and the aqueous phase was re-extracted with heptane (2 × 20 mL). The combined organic phases were washed with water (50 mL), dried over MgSO4, and the solvent was removed under vacuum to provide a crude product mixture (1.03 g, about 3.60 mmol, about 97% yield). It is a colorless oily substance. The yield approximation was determined from the acetylated CNSL mixture in two steps.

[0130] Figure 5 The CNSL heptyloctyl aldehyde is shown to be decarbonylated into a saturated alkane.

[0131] 1 H NMR (300 MHz, CDCl3) δ 7.29 – 7.20 (m, 1H), 7.01 (d, J = 7.6 Hz,1H), 6.90 – 6.81 (m, 2H), 6.77 – 6.65 (m, 0H), 2.65 – 2.53 (m, 2H), 1.60 (p, J = 4.7, 6.3 Hz, 2H), 1.35 (s, 9H), 1.33 – 1.22 (m, 8H), 0.88 (t, J = 6.6 Hz, 3H).

[0132] 13C NMR (75 MHz, CDCl3) δ 177.08, 176.71, 151.34, 151.10, 151.10,144.60, 129.01, 125.67, 121.33, 118.60, 39.05, 35.80, 31.96, 31.82, 31.78,31.32, 29.70, 29.35, 29.31, 29.18, 27.17, 27.17, 27.13, 22.69, 14.12.

[0133] Mixture of pentyl alkane: Heptane (10 mL) was added to a crude CNSL aldehyde mixture (0.510 g, approximately 1.78 mmol), and the solution was stirred under an argon atmosphere for 5 minutes. Palladium on carbon (10 wt%, 0.110 g, 0.1 mmol, 5 mol%) was then added, and the reaction mixture was heated under reflux for 24 hours, at which point ¹H NMR analysis indicated the reaction was complete. After cooling to room temperature, ethanol (20 mL) was added, and the reaction mixture was hydrogenated at room temperature under a hydrogen atmosphere (1 atm) for 16 hours. The reaction mixture was then filtered through diatomaceous earth, washed with ethanol (2 × 20 mL), and the combined filtrates were solvent-removed under vacuum to provide a crude product, a colorless oil. The crude product was dissolved in heptane (20 mL) and washed with a saturated aqueous solution of NaHCO3. The aqueous phase was redissolved with heptane (2 × 10 mL), and the combined organic matter was washed with water, dried over MgSO4, and the solvent was removed under vacuum to provide the crude product (0.45 g, approximately 1.75 mmol, approximately 98% yield). It is a colorless oily substance that is used without further purification. The yield approximation was determined from the acetylated CNSL mixture in four steps.

[0134] Figure 6 The CNSL pentylhexyl aldehyde is shown to be decarbonylated into a saturated alkane.

[0135] 1 H NMR (400 MHz, CDCl3) δ 7.22 – 7.15 (m, 1H), 6.96 (d, J = 7.7 Hz,1H), 6.83 – 6.75 (m, 2H), 6.69 (d, J = 2.0 Hz, 0H), 6.60 (t, J = 2.0 Hz, 0H),2.57 – 2.49 (m, 2H), 1.54 (p,J = 7.7 Hz, 2H), 1.28 (s, 9H), 1.27 – 1.23 (m, 4H), 0.85 – 0.77 (m, 3H).

[0136] 13 C NMR (101 MHz, CDCl3) δ 177.16, 176.79, 151.30, 151.06, 145.31,144.62, 129.02, 125.68, 121.35, 121.33, 119.24, 118.64, 118.59, 112.49,99.98, 77.35, 77.24, 77.03, 76.72, 39.22, 39.10, 39.05, 35.79, 35.75, 33.43,31.95, 31.80, 31.52, 31.31, 30.98, 30.75, 29.72, 29.30, 29.16, 27.24, 27.17, 27.13, 22.72, 22.68, 22.53, 22.49, 22.37, 14.11, 14.04, 14.02.

[0137] Reverse hydroformylation of aldehyde mixtures: The method is adapted from the literature (Journal of the American Chemical Society ... J. Am. Chem. Soc. (2018, 140, 32, 10126–10130) Add [Rh(COD)OMe]2 (19.0 mg, 0.040 mmol), bisphosphine ligand (46.0 mg, 0.008 mmol), 3-methoxybenzoic acid (12.0 mg, 0.008 mmol), and toluene (4.0 mL) to a sealed 50 mL volumetric tube purged with argon. After stirring for 3 minutes, add N,N-dimethylacrylamide (630 mL) sequentially. L (600 mg, 6.0 mmol) and an aldehyde mixture (0.608 g, approx. 1.90 mmol). The reaction tube was sealed and the reaction mixture was stirred at 90 °C for 24 hours. The solvent was then removed under vacuum, and the residue was dissolved in heptane (100 mL). The heterogeneous suspension was then filtered, washed with heptane (2 × 10 mL), and the combined organic matter was washed with water (2 × 100 mL), and then with a saturated aqueous solution of NaHCO3 (100 mL). The combined aqueous wash was re-extracted with heptane (2 × 50 mL), washed with water (50 mL), and then dried over MgSO4 and filtered directly through a silica gel pad (approx. 20 g). The silica gel pad was then washed with a solution of EtOAc:n-hexane (2:10) (2 × 50 mL), and the solvent was removed under vacuum to provide the product (0.512 g, approx. 1.80 mmol, approx. 99%). It is a pale yellow oily substance.

[0138] The yield approximation was determined from the acetylated CNSL mixture in two steps. NMR showed that the material contained approximately 90% of the desired terminal unsaturated product combined with approximately 7% of the fully saturated decarbonylated product and approximately 3% of the internally unsaturated byproduct.

[0139] Figure 7 The reverse hydroformylation reaction of an aldehyde mixture is shown.

[0140] 1 H NMR (300 MHz, CDCl3) δ 7.29 (s, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.94– 6.81 (m, 2H), 6.79 – 6.64 (m, 0H), 5.80 (ddt, J = 6.7, 10.2, 16.9 Hz, 1H), 5.08 – 4.88 (m, 2H), 2.64 – 2.53 (m, 2H), 2.04 (q, J = 6.9 Hz, 2H), 1.70 –1.51 (m, 2H), 1.45 – 1.34 (m, 13H), 0.88 (t, J = 6.5 Hz, 0H).

[0141] 13C NMR (75 MHz, CDCl3) δ 177.11, 151.09, 139.02, 138.99, 129.04,125.65, 121.32, 118.64, 118.59, 114.29, 39.05, 35.71, 33.69, 31.94, 31.30,31.12, 29.72, 29.70, 29.68, 29.50, 29.38, 28.79, 28.76, 27.17, 27.12, 22.71,14.14。

[0142] One-pot molecular homogenization ： 5-Heptylphenyl-1,3-diol (also known as 5-heptylresorcinol, sphaerophorol, or spherol) Add [Ir(OMe)(1,5-COD)]₂ (51.2 mg, 0.079 mmol, approx. 1 mol%) and bis(pinacol)diboron (2.170 g, 8.55 mmol, 1.15 equivalence) to a sealed 50 mL volumetric tube purged with argon, followed by 4,4'-di-tert-butyl-2,2'-bipyridine (43.1 mg, 0.16 mmol, 2 mol%). Stir the solid while purging the tube with argon for 5 minutes, and add the aforementioned product (2.11 g, approx. 7.37 mmol) via pipette. Rinse the pipette with n-hexane (2 × 0.5 mL) and ensure complete transfer of material to the reaction vessel. Purge the tube with argon for another 1 minute, seal, and heat to 110 °C with stirring for 2 hours. After this time, NMR analysis showed the reaction was complete. Cool the tube in an ice bath and slowly add ethanol (10 mL) in portions. Remove the ice bath and transfer the solution to a 250 mL flask, rinsing with ethanol (2 × 20 mL) to ensure complete transfer. Then, a freshly prepared urea peroxide solution (2.48 g, 26.4 mmol) in ethanol (100 mL) is slowly added dropwise over a 1-hour period. After this time, NMR analysis confirms the completion of the reaction, and 20 mL of saturated sodium thiosulfate aqueous solution is added, and the mixture is stirred for 5 minutes. After this time, 50 mL of 10 wt% NaOH aqueous solution is added, and the resulting solution is stirred at room temperature for 2 hours until the reaction is confirmed to be complete by NMR analysis. The solution is then acidified to pH < 3 with 1 M HCl aqueous solution, causing the solution color to change from deep red to pale yellow. The mixture is extracted into ethyl acetate (3 × 50 mL), and the combined extracts are washed sequentially with water (100 mL), then with saturated NaHCO3 aqueous solution (100 mL), followed by washing with brine (100 mL). The organic phase was then dried over MgSO4, and the solvent was removed under vacuum to provide a crude product, which was then chromatographically separated by a 0% to 30% (EtOAc: n-hexane) gradient elution to provide the product 5-heptylphenyl-1,3-diol (1.23 g, 5.91 mmol, 83% yield calculated by CNSL). It is an amber-colored oily substance that crystallizes when left to stand at room temperature.

[0143] Yields were calculated from the earliest known pure precursor (the initial CNSL mixture).

[0144] Figure 8 One-pot molecular homogenization is shown to provide 5-heptylphenyl-1,3-diol.

[0145] 1H NMR (300 MHz, CDCl3) δ 6.24 (d, J = 1.7 Hz, 2H), 6.18 (t, J = 2.2Hz, 1H), 5.03 (s, 2H), 2.54 –2.42 (m, 2H), 1.77 (s, 2H), 1.56 (p, J = 7.1 Hz,2H), 1.33 – 1.22 (m, 8H), 0.88 (t, J = 6.6 Hz, 3H)。

[0146] 13 C NMR (75 MHz, CDCl3) δ 156.55, 146.17, 108.04, 100.13, 35.82,31.80, 31.06, 29.24, 29.16, 22.66, 14.10。

[0147] 5-Pentylphenyl-1,3-diol (also known as oleol or 5-pentylresorcinol) : Add [Ir(OMe)(1,5-cod)]₂ (9.7 mg, 0.015 mmol, 1.5 mol%), bis(pinacol)diboron (412 mg, 1.62 mmol, 1 equivalent) to a sealed 50 mL volumetric tube purged with argon, followed by 4,4'-di-tert-butyl-2,2'-bipyridine (8.1 mg, 0.030 mmol, 2 mol%) and the aforementioned product (250 mg, approximately 0.970 mmol). The tube was then purged with argon again for 1 minute, and 0.5 mL of n-hexane was added to improve mixing. The tube was then sealed and heated to 110 °C with stirring for 2 hours, after which NMR analysis showed the reaction was complete. The tube was then cooled in an ice bath, and ethanol (10 mL) was added slowly in portions. Remove the ice bath and slowly add dropwise a freshly prepared urea peroxide (470 mg, 5 mmol) solution in ethanol (30 mL) over a 2-hour period. After this time, NMR analysis confirmed the completion of the reaction, and 2 mL of saturated sodium thiosulfate solution was added. The mixture was stirred for 5 minutes, after which the contents of the reaction flask were poured into an Erlenmeyer flask containing 40 mL of 1 M NaOH aqueous solution, and the resulting solution was stirred at room temperature for 1 hour. The solution was then acidified with 1 M HCl aqueous solution to pH < 3, causing the solution color to change from deep red to pale yellow. The mixture was extracted into ethyl acetate (3 × 50 mL), and the combined extracts were washed twice with 1 M HCl aqueous solution (100 mL), then with saturated NaHCO3 aqueous solution (100 mL), followed by washing with brine (100 mL). The organic phase was dried over MgSO4 and the solvent was removed under vacuum to provide a crude product, which was then chromatographically separated by a 0% to 30% (EtOAc: n-hexane) gradient elution to provide 5-pentylphenyl-1,3-diol (0.112 g, 0.621 mmol, 62% yield calculated by CNSL). It is a pale yellow oily substance that crystallizes when left to stand at room temperature for a long time. Yields were calculated from the earliest known pure precursor (the initial CNSL mixture).

[0148] Figure 9 One-pot molecular homogenization is shown to provide 5-pentylphenyl-1,3-diol.

[0149] 1 H NMR (400 MHz, CDCl3) δ 6.51 (s, 2H), 6.30 – 6.20 (m, 2H), 6.17 (s,1H), 2.46 – 2.32 (m,2H), 1.49 (p, J= 7.6 Hz, 2H), 1.30 – 1.21 (m, 4H), 0.85(t, J = 6.9 Hz, 3H).

[0150] Although the subject matter of this disclosure (including aspects one through six), encompassing various methods, compounds, and / or formulations manufactured according to said methods, and / or the compounds and / or formulations themselves, has been described in detail with respect to specific embodiments and / or examples thereof, variations, modifications, and equivalents of these embodiments will readily occur to those skilled in the art upon understanding the foregoing. Therefore, the scope of this disclosure should be determined by the scope of the claims and any equivalents thereof, which are appended herein. Claims (as amended under Article 19 of the Treaty) 1. A method for producing cannabinoids and / or cannabinoid precursors and / or derivatives thereof from cashew nut shell liquid (CNSL), wherein the CNSL comprises cashew acid, cashew phenol, and cashew diol, the method comprising the steps described above: (a) Decarboxylating the cashew acid to provide synthetic cashew phenol; (b) Protecting the cashew nut bicarbonate and synthetic cashew nut ... (c) Cleavage of the olefinic bonds of acetylated cardiacoside and acetylated cardiacol, wherein the cleavage provides a CNSL aldehyde, including in one embodiment, providing a CNSL aldehyde by ozone decomposition of acetylated cardiacoside and acetylated cardiacol; and (d) Defunctionalizing the CNSL aldehyde, including decarbonylating the CNSL aldehyde to provide saturated or unsaturated alkylated CNSL hydrocarbons. 2. The method of claim 1, wherein step (b) comprises protection using at least one of the following protective functional groups: methanesulfonate, toluenesulfonate, and acetal. 3. The method according to claim 1 or claim 2, wherein step (c) comprises cleavage of at least one oxidizing and / or non-oxidizing olefin via the group consisting of: dihydroxylation, RuCl3-mediated method, Oxone-mediated method, periodate-mediated method, and Grubbs olefin metathesis reaction. 4. The method according to any one of claims 1 to 3, wherein step (d) occurs via a synthetic pathway step (d1), wherein step (d1) comprises reacting the CNSL aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene. 5. The method of claim 4, wherein step (d1) occurs between 80°C and 100°C and lasts for between 10 minutes and 24 hours. 6. The method according to any one of claims 1 to 3, wherein step (d) occurs via a synthetic pathway step (d2), wherein step (d2) comprises reacting the CNSL aldehyde with [Ir(coe)2Cl]2, PPh3, and 2MeTHF. 7. The method of claim 6, wherein step (d2) occurs between 80°C and 150°C and lasts for between 10 minutes and 180 minutes. 8. The method according to claim 6 or claim 7, wherein step (d2) comprises treating or exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation. 9. The method according to any one of claims 1 to 8, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further hydrogenated to provide a saturated alkylated CNSL hydrocarbon. 10. The method according to any one of claims 1 to 8, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length. 11. The method according to any one of claims 1 to 10, wherein the cannabinoid precursor comprises 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol. 12. The method of claim 11, wherein 5-pentylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THC), and / or wherein 5-heptylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THCP). 13. A method for manufacturing cannabinoids and / or cannabinoid precursors and / or derivatives thereof, the method comprising the steps described above: (a) Protecting cashew nut bicarbonate and / or cashew phenol, providing protected cashew nut bicarbonate and / or protected cashew phenol, including providing acetylated cashew nut bicarbonate and acetylated cashew phenol by acetylation of said cashew nut bicarbonate and / or cashew phenol. (b) Cleavage of the olefinic bonds of acetylated cashew nut biphenol and acetylated cashew phenol, wherein cleavage provides an aldehyde, including in one embodiment ozone decomposition of acetylated cashew nut biphenol and acetylated cashew phenol to provide an aldehyde; (c) Defunctionalizing the aldehyde, including decarbonylating the aldehyde to provide saturated or unsaturated alkylated hydrocarbons. 14. The method of claim 14, wherein at least one of cashew nut biphenol and / or cashew phenol is derived from cashew nut shell liquid (CNSL). 15. The method according to claim 13 or claim 14, wherein step (b) comprises protection using at least one of the following protective functional groups: methanesulfonate, toluenesulfonate, and acetal. 16. The method according to any one of claims 13 to 15, wherein step (c) comprises olefin cleavage via at least one oxidizing and / or non-oxidizing olefin from the group consisting of: dihydroxylation, RuCl3-mediated method, Oxone-mediated method, periodate-mediated method, and Grubbs olefin metathesis reaction. 17. The method according to any one of claims 13 to 16, wherein step (c) occurs via a synthetic pathway step (c1), wherein step (c1) comprises reacting the CNSL aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene. 18. The method of claim 17, wherein step (c1) occurs between 80°C and 100°C and lasts for between 10 minutes and 24 hours. 19. The method according to any one of claims 13 to 16, wherein step (c) occurs via a synthetic pathway step (c2), wherein step (c2) comprises reacting the CNSL aldehyde with [Ir(coe)2Cl]2, PPh3, and 2MeTHF. 20. The method of claim 19, wherein step (c2) occurs between 80°C and 150°C and lasts for between 10 minutes and 180 minutes. 21. The method according to claim 19 or claim 20, wherein step (c2) comprises treating or exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation. 22. The method according to any one of claims 13 to 21, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further hydrogenated to provide a saturated alkylated CNSL hydrocarbon. 23. The method according to any one of claims 13 to 21, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length. 24. The method according to any one of claims 13 to 23, wherein the cannabinoid precursor comprises 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol. 25. The method of claim 24, wherein 5-pentylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THC), and / or wherein 5-heptylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THCP). 26. A method for manufacturing a precursor compound for cannabinoid production and / or a method for manufacturing cannabinoids, the method comprising using cashew acid and / or cashew phenol and / or cashew diol and / or aromatic hydrocarbon and / or symmetrical resorcinol, wherein the cashew acid and / or the cashew phenol and / or the cashew diol and / or the aromatic hydrocarbon and / or the symmetrical resorcinol are derived from cashew nut shell liquid (CNSL) and / or its chemical components. 27. The method of claim 26, wherein the precursor compound comprises 5-pentylresorcinol and / or 5-heptylresorcinol. 28. The method of claim 27, wherein 5-pentylresorcinol is used in the downstream processing of the manufacture of the cannabinoid tetrahydrocannabinol (THC), and / or wherein 5-heptylresorcinol is used in the downstream processing of the manufacture of the cannabinoid tetrahydrocannabinol (THCP).

Claims

1. A method for producing cannabinoids and / or cannabinoid precursors and / or derivatives thereof from cashew nut shell liquid (CNSL), wherein the CNSL comprises cashew acid, cashew phenol, and cashew diol, the method comprising the steps described above: (a) Decarboxylating the cashew acid to provide synthetic cashew phenol; (b) Protecting the cashew nut bicarbonate and synthetic cashew nut ... (c) Cleavage of the olefinic bonds of acetylated cardiacoside and acetylated cardiacol, wherein the cleavage provides a CNSL aldehyde, including in one embodiment, providing a CNSL aldehyde by ozone decomposition of acetylated cardiacoside and acetylated cardiacol; and (d) Defunctionalizing the CNSL aldehyde, including decarbonylating the CNSL aldehyde to provide saturated or unsaturated alkylated CNSL hydrocarbons.

2. The method of claim 1, wherein step (b) comprises protection using at least one of the following protective functional groups: methanesulfonate, toluenesulfonate, and acetal.

3. The method according to claim 1 or claim 2, wherein step (c) comprises cleavage of at least one oxidizing and / or non-oxidizing olefin via the group consisting of: dihydroxylation, RuCl3-mediated method, Oxone-mediated method, periodate-mediated method, and Grubbs olefin metathesis reaction.

4. The method according to any one of claims 1 to 3, wherein step (d) occurs via a synthetic pathway step (d1), wherein step (d1) comprises reacting the CNSL aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene.

5. The method of claim 4, wherein step (d1) occurs between 80°C and 100°C and lasts for between 10 minutes and 24 hours.

6. The method according to any one of claims 1 to 3, wherein step (d) occurs via a synthetic pathway step (d2), wherein step (d2) comprises reacting the CNSL aldehyde with [Ir(coe)2Cl]2, PPh3, and 2MeTHF.

7. The method of claim 6, wherein step (d2) occurs between 80°C and 150°C and lasts for between 10 minutes and 180 minutes.

8. The method according to claim 6 or claim 7, wherein step (d2) comprises treating or exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation.

9. The method according to any one of claims 1 to 8, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further hydrogenated to provide a saturated alkylated CNSL hydrocarbon.

10. The method according to any one of claims 1 to 8, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length.

11. The method according to any one of claims 1 to 10, wherein the cannabinoid precursor comprises 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

12. The method of claim 11, wherein 5-pentylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THC), and / or wherein 5-heptylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THCP).

13. A method for manufacturing cannabinoids and / or cannabinoid precursors and / or derivatives thereof, the method comprising the steps described above: (a) Protecting cashew nut bicarbonate and / or cashew phenol, providing protected cashew nut bicarbonate and / or protected cashew phenol, including providing acetylated cashew nut bicarbonate and acetylated cashew phenol by acetylation of said cashew nut bicarbonate and / or cashew phenol. (b) Cleavage of the olefinic bonds of acetylated cashew nut biphenol and acetylated cashew phenol, wherein cleavage provides an aldehyde, including in one embodiment ozone decomposition of acetylated cashew nut biphenol and acetylated cashew phenol to provide an aldehyde; (c) Defunctionalizing the aldehyde, including decarbonylating the aldehyde to provide saturated or unsaturated alkylated hydrocarbons.

14. The method of claim 14, wherein at least one of cashew nut biphenol and / or cashew phenol is derived from cashew nut shell liquid (CNSL).

15. The method according to claim 13 or claim 14, wherein step (b) comprises protection using at least one of the following protective functional groups: methanesulfonate, toluenesulfonate, and acetal.

16. The method according to any one of claims 13 to 15, wherein step (c) comprises olefin cleavage via at least one oxidizing and / or non-oxidizing olefin from the group consisting of: dihydroxylation, RuCl3-mediated method, Oxone-mediated method, periodate-mediated method, and Grubbs olefin metathesis reaction.

17. The method according to any one of claims 13 to 16, wherein step (c) occurs via a synthetic pathway step (c1), wherein step (c1) comprises reacting the CNSL aldehyde with DMMA, Rh(COD)OMe, 3MeOBzOH, a bisphosphine ligand, and toluene.

18. The method of claim 17, wherein step (c1) occurs between 80°C and 100°C and lasts for between 10 minutes and 24 hours.

19. The method according to any one of claims 13 to 16, wherein step (c) occurs via a synthetic pathway step (c2), wherein step (c2) comprises reacting the CNSL aldehyde with [Ir(coe)2Cl]2, PPh3, and 2MeTHF.

20. The method of claim 19, wherein step (c2) occurs between 80°C and 150°C and lasts for between 10 minutes and 180 minutes.

21. The method according to claim 19 or claim 20, wherein step (c2) comprises treating or exposing the CNSL aldehyde to Pd / C (palladium on carbon catalyst) followed by hydrogenation.

22. The method according to any one of claims 13 to 21, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further hydrogenated to provide a saturated alkylated CNSL hydrocarbon.

23. The method according to any one of claims 13 to 21, wherein the unsaturated alkylated CNSL hydrocarbon is an olefin, and further subjected to ozone decomposition and defunctionalization (including decarboxylation) to shorten the alkyl chain length.

24. The method according to any one of claims 13 to 23, wherein the cannabinoid precursor comprises 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol.

25. The method of claim 24, wherein 5-pentylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THC), and / or wherein 5-heptylresorcinol is used in the downstream processing for the manufacture of the cannabinoid tetrahydrocannabinol (THCP).

26. A method for manufacturing a precursor compound for cannabinoid production and / or a method for manufacturing cannabinoids, the method comprising using cashew acid and / or cashew phenol and / or cashew diol and / or aromatic hydrocarbon and / or symmetrical resorcinol, wherein the cashew acid and / or the cashew phenol and / or the cashew diol and / or the aromatic hydrocarbon and / or the symmetrical resorcinol are derived from cashew nut shell liquid (CNSL) and / or its chemical components.

27. The method of claim 26, wherein the precursor compound comprises 5-pentylresorcinol and / or 5-heptylresorcinol.

28. The method of claim 27, wherein 5-pentylresorcinol is used in the downstream processing of the manufacture of the cannabinoid tetrahydrocannabinol (THC), and / or wherein 5-heptylresorcinol is used in the downstream processing of the manufacture of the cannabinoid tetrahydrocannabinol (THCP).

29. The precursor compounds 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol, manufactured by the method according to any one of claims 1 to 10.

30. Cannabinoids tetrahydrocannabinol (THC) and / or tetrahydrocannabinone (THCP), manufactured by the method according to any one of claims 1 to 12.

31. The precursor compound according to claim 29 and / or the cannabinoid according to claim 30, used as a medicament for treating, preventing and / or improving diseases and / or medical conditions.

32. The precursor compounds 5-heptylphenyl-1,3-diol and / or 5-pentylphenyl-1,3-diol, manufactured by the method according to any one of claims 13 to 24.

33. Cannabinoids tetrahydrocannabinol (THC) and / or tetrahydrocannabinone (THCP), manufactured by the method according to any one of claims 13 to 25.

34. The precursor compound according to claim 32 and / or the cannabinoid according to claim 33, used as a medicament for treating, preventing and / or improving diseases and / or medical conditions.

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