A method of manufacturing precursor compounds for manufacturing cannabinoids and / or methods of manufacturing cannabinoids

Abstract

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

Description

[0001] A METHOD OF MANUFACTURING PRECURSOR COMPOUNDS FOR MANUFACTURING CANNABINOIDS AND / OR METHODS OF MANUFACTURING CANNABINOIDS

[0002] FIEED OF DISCEOSURE

[0003] Generally, this disclosure relates to the manufacturing of cannabinoids and / or precursors of cannabinoids. Particularly, this disclosure relates to use of cashew nut shell liquid (CNSL) and / or chemical components thereof in a method of manufacturing cannabinoids and / or precursors of cannabinoids. In certain embodiments, this disclosure relates to the use of a cardanol and / or cardol and / or an arene and / or a symmetrical resorcinol in the manufacturing of cannabinoids and / or precursors of cannabinoids. In certain further example embodiments, this disclosure relates to use of a cardanol and / or cardol and / or an arene and / or a symmetrical resorcinol, at least one of which being derived from CNSL, in the manufacturing of cannabinoids and / or precursors of cannabinoids. This disclosure extends to cannabinoids and / or precursors of cannabinoids themselves. Particularly, this disclosure extends to cannabinoids and / or precursors of cannabinoids themselves as manufactured according to the methods described herein.

[0004] BACKGROUND

[0005] Recently, there has been a move away from using petroleum or petroleum-based products as starting reagents in organic synthesis of commercially relevant chemical products. In order to employ sustainable carbon sources as starting reagents for organic synthesis researchers have considered the use of biomass, particularly non-edible biomass that would otherwise be discarded. As such, the valorisation of non-edible biomass and / or waste product biomass has been a much-researched topic.

[0006] One non-edible biomass source that has been a topic of much research is cashew nut shell liquid (CNSL). CNSL is known to have little commercial value on its own, however, CNSL is rich in phenolics and is known as a non-edible biomass-derived chemical feedstock for the production of paints, resins, polymers, and surfactants. Cashew crop is a common high value crop in many developing countries and valorising any waste product produced by its cultivation could provide much needed economic benefits and / or upliftment in such countries.

[0007] Furthermore, consumers have become reluctant to purchase non-sustainably derived products.

[0008] CNSL typically includes a mixture of phenolic compounds. The primary constituents of CNSL include three structurally related anacardic acids and three structurally related cardanols, with trace amounts of three structurally related cardols. The cardols are a very minor constituent of CNSL, but it is a chemical compound that may be utilized as a building block for producing higher value chemicals via appropriate downstream organic syntheses.

[0009] Since the three structurally related cardols are a very minor constituent of CNSL, obtaining sufficient amounts for downstream processing into higher value compounds is arduous and expensive. Alternative synthetic routes for producing cardols are known to be expensive and time consuming. The current market price of purchasing cardol is in the region of US$660 for 10 grams which is viewed as prohibitively high therein stifling its use and application in the production of downstream higher value compounds.

[0010] Research regarding the manufacture and use of cannabinoids has increased over the last decade as cannabis has been, and continues to be, legalised in an increasing number of jurisdictions worldwide. In a human or animal body, cannabinoids target cannabinoid receptors CB and CB2 as part of their biochemical and / or physiological mechanisms of action. Within the medical field, cannabinoids are known for their use in the treatment and / or prevention and / or amelioration of nausea, pain and / or spasticity. Two known United States Food and Drug Administration approved pharmaceuticals are derived from cannabinoids, namely Marinol® and Syndros®. Both Marinol® and Syndros®, contain synthetic -9-tetrahydrocannabinol (THC) also known as dronabinol. Another pharmaceutical, Cesamet®, contains nabilone, which is derived from tetrahydrocannabiphorol (THCP). Both dronabinol and nabilone are used to treat nausea and vomiting caused by cancer chemotherapy.

[0011] The most widely known cannabinoids are those found in cannabis plants, and as such, there has been an increase in the domestic and commercial cultivation of this crop. There are reports regarding the negative environmental impact of cannabis cultivation, as well as the safety issues surrounding use, harvest, and disposal of waste products that might contain phytochemicals that impede and / or impact motor function and / or cognition. The unregulated disposal of potentially harmful waste, including biomass waste from cannabis plants, provides a safety concern to the public. Further, plant material is not used as the source of tetrahydrocannabinol (THC) in pharmaceutical applications since the separation from more than 100 other cannabinoidsis extremely difficult, and as such, in pharmaceutical applications, the THC is typically synthesized from synthetic olivetol.

[0012] There is a need to ameliorate the negative environmental and safety impact of cannabis cultivation. There is a need to provide a method of manufacturing cannabinoids (including their precursors) utilizing a non-edible biomass source, wherein such biomass may also be a waste product, and wherein the waste product does not in itself contain chemicals in high enough concentration to elicit a response in motor function and / or cognition when consumed by a human or animal. There is a need to ameliorate at least one of the disadvantages above, or otherwise known in the prior art.

[0013] SUMMARY

[0014] Generally, this disclosure relates to methods of manufacturing cannabinoids (including cannabinoid precursors) and / or derivatives thereof.

[0015] Broadly, any one or more of the methods herein may in certain embodiments provide methods of valorising cashew nut shell liquid (CNSU) and / or a chemical component thereof.

[0016] Broadly, the methods may, in certain embodiments, each include use of cashew nut shell liquid (CNSU), and / or a chemical component thereof, as a raw material source. In embodiments where a chemical component of CNSU is utilized it is to be understood that such chemical component may be directly derived from CNSL. Alternatively and / or additionally, it is to be understood that such chemical component may be synthetically derived. Alternatively and / or additionally, it is to be understood that such chemical component may be procured from a source different from CNSL. The cashew nut shell liquid (CNSL), and / or a chemical component thereof may include an anacardic acid and / or a cardanol and / or a cardol and / or an arene and / or a symmetrical resorcinol.

[0017] In accordance with a first aspect of this disclosure there is provided a method of manufacturing cannabinoids and / or precursors of cannabinoids and / or derivatives thereof. The method may include use of an anacardic acid and / or a cardanol and / or a cardol. In certain example embodiments, at least one of the anacardic acid and / or the cardanol and / or the cardol are derived from CNSL and / or a chemical component thereof. This disclosure extends to cannabinoids and / or precursors of cannabinoids themselves. Particularly, this disclosure extends to cannabinoids and / or precursors of cannabinoids themselves as manufactured according to the methods described herein.

[0018] The precursor compounds for manufacturing cannabinoids may include cashew nut derived phenolic compounds.

[0019] The precursor compounds may include, but not limited to, 5 -pentylresorcinol (olivetol) and / or 5- heptylresorcinol (spherophorol), both which may be used for downstream processing in the manufacturing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabiphorol (THCP), respectively.

[0020] In accordance with a second aspect of this disclosure there is provided a method of manufacturing cannabinoids and / or precursors of cannabinoids and / or derivatives thereof from cashew nut shell liquid (CNSL), the CNSL including anacardic acids, cardanols, and cardol, the method comprising the following steps:

[0021] (a). decarboxylation of the anacardic acids to provide synthetic cardanols;

[0022] (b). protection of the cardol and synthetic cardanols providing a protected cardol and protected cardanols, including protection by way of acetylation of the cardol and synthetic cardanols providing acetylated cardol and acetylated cardanols;

[0023] (c). cleaving alkene bonds of acetylated cardol and acetylated cardanols, wherein cleavage may provide CNSL aldehydes, including in an embodiment by way of ozonolysis of acetylated cardol and acetylated cardanols to provide CNSL aldehydes;

[0024] (d). defunctionalization of the CNSL aldehydes, including decarbonylation of the CNSL aldehydes to provide saturated and / or unsaturated alkylated CNSL hydrocarbons.

[0025] Step (b) may include protection utilizing at least one of, but not limited to, the following protecting functional groups: mesylate, tosylates and acetals. Step (b) may be optional. Step (c) may include oxidative and / or non-oxidative alkene cleavage, via at least one of, but not limited to, the following group: dihydroxylation, RuCL mediated methods, oxone mediated methods, periodate mediated methods, and Grubbs alkene metathesis.

[0026] Step (d) may take place via at least two different synthetic routes namely Step (d 1 ) and Step (d2) . Both Step (dl) and Step (d2) may be employed in the method according to the disclosure. Alternatively, only one of Step (dl) or Step (d2) may be employed in the method according to the disclosure.

[0027] Step (dl) includes reacting the CNSL aldehydes together with DMAA, Rh(COD)OMe, 3MeOBzOH, xanthphos and toluene. Typically, Step (dl) takes place between 80°C to 100 °C and for a period of time between 10 minutes and 24 hours. Preferred example embodiments of this step are shown herein below.

[0028] Step (dl) provides for unsaturated alkylated CNSL hydrocarbons. Typically, the unsaturated alkylated CNSL hydrocarbons are alkenes.

[0029] The Applicant envisages additional and / or alternative synthetic strategies, including but not limited to, contacting / reacting / exposing CNSL derived / based alcohols, aldehydes and / or carboxylic acids to palladium and / or iridium catalysts.

[0030] Further, the Applicant provides another synthetic strategy including conducting a functional group interconversion reaction to a leaving group, base mediated E2 elimination to obtain an alkene, and cleavage of the alkene.

[0031] Further, the Applicant provides another synthetic strategy including direct dehydration of aldehyde derived hydroxyl using acids including but not limited to p-toluene sulphonic acid and / or propanephosphonic acid anhydride.

[0032] Still further, the Applicant provides another synthetic strategy including condensing a CNSL aldehyde with malonic acid under basic conditions to undergo decarboxylation and alkene isomerization therein providing precursor compounds in accordance with this disclosure.

[0033] Step (d) may be optional.

[0034] There is further provided that the unsaturated alkylated CNSL hydrocarbons are alkenes and may further undergo hydrogenation to provide saturated alkylated CNSL hydrocarbons. It is to be understood that further downstream processing is provided. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0035] There is further provided that the unsaturated alkylated CNSL hydrocarbons are alkenes and may further undergo ozonolysis and defunctionalization (including decarboxylation) to reduce the alkyl chain length. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below. Step (d2) includes reacting the CNSL aldehydes together with [Ir(COD)2Cl]2, PPh,. 2MeTHF. Typically, Step (d2) takes place between 80°C to 150 °C and for a period of time between 10 minutes and 180 minutes. Preferred example embodiments of this step are shown herein below. Step (d2) may alternatively and / or additionally include conducting exposing the CNSL aldehydes to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The Applicant provides other carbon carbon cleavage reactions, preferably metal catalysed, conducted on any of CNSL derived / based alcohols, aldehydes and / or carboxylic acids, to provide saturated linear alkanes.

[0036] Step (d2) provides for saturated alkylated CNSL hydrocarbons.

[0037] The precursors of cannabinoids and / or derivatives thereof according to the method may include 5- heptylbenzene-l,3-diol and / or 5-pentylbenzene-l,3-diol.

[0038] The precursor compounds 5-heptylbenzene-l,3-diol and / or 5-pentylbenzene-l,3-diol may be used for downstream processing in the manufacturing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabiphorol (THCP), respectively.

[0039] It is to be understood that further downstream processing is provided. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0040] In accordance with a third aspect of this disclosure there is provided a method of manufacturing cannabinoids and / or precursors of cannabinoids and / or derivatives, the method comprising the following steps:

[0041] (a). protection of a cardol and / or a cardanol providing a protected cardol and / or a protected cardanol, including protection by way of acetylation of the cardol and / or the cardanol providing acetylated cardol and / or acetylated cardanol;

[0042] (b). cleaving alkene bonds of acetylated cardol and / or acetylated cardanol, wherein cleavage provides aldehydes, including in an embodiment by way of ozonolysis of acetylated cardol and / or acetylated cardanol to provide aldehydes;

[0043] (c). defunctionalization of the aldehydes, including decarbonylation of the aldehydes to provide saturated and / or unsaturated alkylated hydrocarbons.

[0044] The method wherein at least one of the cardol and / or cardanol are from cashew nut shell liquid (CNSL).

[0045] Step (a) may include protection utilizing at least on of, but not limited to, the following protecting functional groups: mesylate, tosylates and acetals. Step (b) may be optional.

[0046] Step (c) may include oxidative and / or non-oxidative alkene cleavage, via at least one of, but not limited to, the following group: dihydroxylation, RuCL mediated methods, oxone mediated methods, periodate mediated methods, and Grubbs alkene metathesis. Step (c) may take place via at least two different synthetic routes namely Step (cl) and Step (c2). Both Step (cl) and Step (c2) may be employed in the method according to the disclosure. Alternatively, only one of Step (cl) or Step (c2) may be employed in the method according to the disclosure.

[0047] Step (cl) includes reacting the aldehydes together with DMAA, Rh(COD)OMe, 3MeOBzOH, xanthphos and toluene. Typically, Step (cl) takes place between 80°C to 100 °C and for a period of time between 10 minutes and 24 hours. Preferred example embodiments of this step are shown herein below.

[0048] Step (cl) provides for unsaturated alkylated hydrocarbons. Typically, the unsaturated alkylated hydrocarbons are alkenes.

[0049] The Applicant provides additional and / or alternative synthetic strategies, including but not limited to, contacting / reacting / exposing CNSL derived / based alcohols, aldehydes and / or carboxylic acids to palladium and / or iridium catalysts.

[0050] Further, the Applicant provides another synthetic strategy including conducting a functional group interconversion reaction to a leaving group, base mediated E2 elimination to obtain an alkene, and cleavage of the alkene.

[0051] Further, the Applicant provides another synthetic strategy including direct dehydration of aldehyde derived hydroxyl using acids including but not limited to p-toluene sulfonic acid and / or propanephosphonic acid anhydride.

[0052] Still further, the Applicant provides another synthetic strategy including condensing an aldehyde with malonic acid under basic conditions to undergo decarboxylation and alkene isomerization therein providing precursor compounds in accordance with this disclosure.

[0053] Step (c) may be optional.

[0054] There is further provided that the unsaturated alkylated hydrocarbons are alkenes and may further undergo hydrogenation to provide saturated alkylated hydrocarbons. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0055] There is further provided that the unsaturated alkylated hydrocarbons are alkenes and may further undergo ozonolysis and defunctionalization (including decarboxylation) in order to reduce the alkyl chain length. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0056] Step (c2) includes reacting the aldehydes together with [Ir(COD)2Cl]2, PPh ,. 2MeTHF. Typically, Step (c2) takes place between 80°C to 150 °C and for a period of time between 10 minutes and 180 minutes. Preferred example embodiments of this step are shown herein below. Step (c2) may alternatively and / or additionally include conducting exposing the CNSL aldehydes to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The Applicant envisages other carbon carbon cleavage reactions, preferably metal catalysed, conducted on any of CNSL derived / based alcohols, aldehydes and / or carboxylic acids, to provide saturated linear alkanes.

[0057] Step (c2) provides for saturated alkylated hydrocarbons.

[0058] The precursors of cannabinoids and / or derivatives thereof according to the method may include 5- heptylbenzene-l,3-diol and / or 5-pentylbenzene-l,3-diol.

[0059] The precursor compounds 5-heptylbenzene-l,3-diol and / or 5 -pentylbenzene -1,3 -diol may be used for downstream processing in the manufacturing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabiphorol (THCP), respectively.

[0060] It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0061] In accordance with a fourth aspect of this disclosure there is provided for use of cannabinoids and / or precursors of cannabinoids and / or derivatives thereof manufactured according to the first to third aspects in the manufacture of a medicament for treatment, prevention and / or amelioration of a disease and / or medical condition.

[0062] In accordance with a fifth aspect of this disclosure there is provided the cannabinoids and / or precursors of cannabinoids and / or derivatives thereof manufactured according to the first to third aspects for use as a medicament for treatment, prevention and / or amelioration of a disease and / or medical condition.

[0063] In accordance with a sixth aspect of this disclosure there is provided a method of treatment, prevention and / or amelioration of a disease and / or medical condition utilizing the cannabinoids and / or precursors of cannabinoids and / or derivatives thereof manufactured according to the methods described herein.

[0064] Non-limiting examples of the cannabinoids and / or their derivatives, and their method of production, are provided herein below which is incorporated in this summary by way of reference thereto to avoid repetition. There is further provided for a method embodied in any one or more of Figures 1 to 9 herein.

[0065] There is further provided for any of the first to the sixth aspects of this disclosure substantially as herein described, illustrated and / or exemplified with reference to any one of the descriptions and / or examples and / or photos and / or images and / or reaction schemes and / or diagrammatic drawings herein.

[0066] BRIEF DESCRIPTION OF DRAWINGS

[0067] Embodiments of the disclosure will be described below by way of example only and with reference to the accompanying diagrammatic drawings, photos, and / or chemical reaction schemes and which are not to be construed as limiting the scope of the disclosure or any part thereof.

[0068] Figure 1 shows a reaction scheme for a method of valorising cashew nut shell liquid (CNSL) in accordance with this disclosure. Figure 2 show shows the acetylation of cashew nut shell liquid (CNSL).

[0069] Figure 3 shows ozonolysis of the acetylated CNSL.

[0070] Figure 3 shows ozonolysis of terminally unsaturated CNSL.

[0071] Figure 5 shows decarbonylation of CNSL heptaoctyl aldehydes to saturated alkanes.

[0072] Figure 6 shows decarbonylation of CNSL pentahexyl aldehydes to saturated alkanes.

[0073] Figure 7 shows the retro-hydroformylation of aldehyde mixture.

[0074] Figure 8 shows one pot molecular homogenization to provide 5-heptylbenzene-l,3-diol.

[0075] Figure 9 shows one pot molecular homogenization to provide 5-pentylbenzene-l,3-diol.

[0076] DETAILED DESCRIPTION

[0077] The general provisions of the Summary are repeated herein by way of reference thereto and are not necessarily repeated in full to avoid repetition. The detailed description and examples herein below will include particular embodiments of this disclosure and should not be considered as limiting in any way. Several alternatives may be envisioned by a person skilled in the art which does not depart from the scope of this disclosure.

[0078] Cashew nut shell liquid (CNSL) has been identified as a sustainably produced biomass and chemical feedstock. Utilising CNSL in the methods of this disclosure and the chemicals and / or compositions produced by exercising the methods is extremely cost effective when compared to the existing state of the art methods providing the same or similar compounds (for example cardol and / or derivatives thereof, cardanol and / or derivatives thereof, and cannabinoids (including precursors) and derivatives thereof), and provides for simplification of organic synthetic routes reducing inter alia the number of process steps, the solvents utilized, the energy expended, and the time expended. The Applicant believes that the methods according to this disclosure provide a technical solution to the technical problems experienced in the state of the art. Furthermore, there is no hint and / or suggestion in the current state of the art that would prompt the person skilled in the art to consider CNSL as a feedstock or starting reagent required to produce the chemicals and / or compositions of this disclosure.

[0079] The primary phenolic constituents of CNSL include, but are not limited to, anacardic acids, cardanols, and 5 -alkyl resorcinols (including cardols), wherein anacardic acids and cardanols are major phenolic constituents and the 5 -alkyl resorcinols (including cardol) is a very minor constituent. Typically, cardols and cardanols may be utilized as building blocks in downstream processes to provide for high value chemical compounds. The phenolics (anacardic acids, cardanols and cardols) were extracted by known organic separation means from CNSL and isolated for further downstream processing, synthesis, functionalization and / or transformation and / or synthetic procedures as described herein.

[0080] The disclosure relates to use of CNSL and / or a chemical component thereof in a method to manufacture cannabinoids and / or derivatives thereof (including precursors of same). This extends to use of such manufactured cannabinoids in the manufacture of a medicament for the treatment of a disease and / or medical condition. The example embodiments disclosed below of the method and the resulting cannabinoids are not to be construed as limiting. Utilizing the CNSL as a raw material source avoids the environmental and safety issues associated with cannabis crop production and associated waste disposal.

[0081] In accordance with a first aspect of this disclosure there is provided a method of manufacturing precursor compounds for manufacturing cannabinoids and / or a method of manufacturing cannabinoids. In certain embodiments, the method include use of CNSL and / or a chemical component thereof, wherein the CNSL may include an anacardic acid, a cardanol, a cardol and / or an arenes and / or and / or a symmetrical resorcinol. The disclosure extends to the precursor compounds and / or the cannabinoids themselves.

[0082] The precursor compounds for manufacturing cannabinoids may include cashew nut derived phenolic compounds.

[0083] The cannabinoids and / or precursors of cannabinoids and / or derivatives thereof according to the method may include 5-heptylbenzene-l,3-diol and / or 5-pentylbenzene-l,3-diol.

[0084] Typically, the precursor compounds many include, but not limited to, 5 -pentylresorcinol and / or 5- heptylresorcinol, both which may be used for downstream processing in the manufacturing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabiphorol (THCP), respectively.

[0085] In accordance with a second aspect of this disclosure there is provided a method of manufacturing cannabinoids and / or derivatives thereof from cashew nut shell liquid (CNSL), the CNSL including anacardic acids, cardanols, and cardols, the method comprising the following steps:

[0086] (a). decarboxylation of the anacardic acids to provide synthetic cardanols;

[0087] (b). protection of the cardols and synthetic cardanols providing a protected cardols and protected cardanols, including protection by way of acetylation of the cardols and synthetic cardanols providing acetylated cardols and acetylated cardanols;

[0088] (c). cleaving alkene bonds of acetylated cardols and acetylated cardanols, wherein cleavage may provide CNSL aldehydes, including in an embodiment by way of ozonolysis of acetylated cardols and acetylated cardanols to provide CNSL aldehydes;

[0089] (d). defunctionalization of the CNSL aldehydes, including decarbonylation of the CNSL aldehydes to provide saturated or unsaturated alkylated CNSL hydrocarbons. Step (b) may include protection utilizing at least on of, but not limited to, the following protecting functional groups: mesylate, tosylates and acetals. Step (b) may be optional.

[0090] Step (c) may include oxidative and / or non-oxidative alkene cleavage, via at least one of, but not limited to, the following group: dihydroxylation, RuCL mediated methods, oxone mediated methods, periodate mediated methods, and Grubbs alkene metathesis.

[0091] Step (d) may take place via at least two different synthetic routes namely Step (d 1 ) and Step (d2) . Both Step (dl) and Step (d2) may be employed in the method according to the disclosure. Alternatively, only one of Step (dl) or Step (d2) may be employed in the method according to the disclosure.

[0092] Step (dl) includes reacting the CNSL aldehydes together with DMAA, Rh(COD)OMe, 3MeOBzOH, xanthphos and toluene. Typically, Step (dl) takes place between 80°C to 100 °C and for a period of time between 10 minutes and 24 hours. Preferred example embodiments of this step are shown herein below.

[0093] Step (dl) provides for unsaturated alkylated CNSL hydrocarbons. Typically, the unsaturated alkylated CNSL hydrocarbons are alkenes.

[0094] The Applicant envisages additional and / or alternative synthetic strategies, including but not limited to, contacting / reacting / exposing CNSL derived / based alcohols, aldehydes and / or carboxylic acids to palladium and / or iridium catalysts.

[0095] Further, the Applicant envisages another synthetic strategy including conducting a functional group interconversion reaction to a leaving group, base mediated E2 elimination to obtain an alkene, and cleavage of the alkene.

[0096] Further, the Applicant envisages another synthetic strategy including direct dehydration of aldehyde derived hydroxyl using acids including but not limited to p-toluene sulpfonic acid and / or propanephosphonic acid anhydride.

[0097] Still further, the Applicant envisages another synthetic strategy including condensing a CNSL aldehyde with malonic acid under basic conditions to undergo decarboxylation and alkene isomerization therein providing precursor compounds in accordance with this disclosure.

[0098] Step (d) may be optional.

[0099] There is further provided that the unsaturated alkylated CNSL hydrocarbons are alkenes and may further undergo hydrogenation to provide saturated alkylated CNSL hydrocarbons. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0100] There is further provided that the unsaturated alkylated CNSL hydrocarbons are alkenes and may further undergo ozonolysis and defunctionalisation (including decarboxylation) to reduce the alkyl chain length. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0101] Step (d2) includes reacting the CNSL aldehydes together with [Ir(COD)2Cl]2, PPh,. 2MeTHF. Typically, Step (d2) takes place between 80°C to 150 °C and for a period of time between 10 minutes and 180 minutes. Preferred example embodiments of this step are shown herein below. Step (d2) may alternatively and / or additionally include conducting exposing the CNSL aldehydes to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The Applicant envisages other carbon carbon cleavage reactions, preferably metal catalysed, conducted on any of CNSL derived / based alcohols, aldehydes and / or carboxylic acids, to provide saturated linear alkanes.

[0102] Step (d2) provides for saturated alkylated CNSL hydrocarbons.

[0103] The cannabinoids and / or precursors of cannabinoids and / or derivatives thereof according to the method may include 5-heptylbenzene-l,3-diol and / or 5-pentylbenzene-l,3-diol.

[0104] Typically, the precursor compounds many include, but not limited to, 5 -pentylresorcinol and / or 5- heptylresorcinol, both which may be used for downstream processing in the manufacturing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabiphorol (THCP), respectively.

[0105] It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0106] In accordance with a third aspect of this disclosure there is provided a method of manufacturing cannabinoids and / or derivatives, the method comprising the following steps:

[0107] (a). protection of a cardol and / or a cardanol providing a protected cardol and / or protected cardanol, including protection by way of acetylation of the cardol and / or cardanol providing acetylated cardol and / or acetylated cardanols;

[0108] (b). cleaving alkene bonds of acetylated cardol and / or acetylated cardanols, wherein cleavage provides aldehydes, including in an embodiment by way of ozonolysis of acetylated cardol and / or acetylated cardanol to provide aldehydes;

[0109] (c). defunctionalisation of the aldehydes, including decarbonylation of the aldehydes to provide saturated or unsaturated alkylated hydrocarbons.

[0110] The method wherein at least one of the cardol and / or cardanols are from cashew nut shell liquid (CNSL).

[0111] Step (a) may include protection utilizing at least on of, but not limited to, the following protecting functional groups: mesylate, tosylates and acetals. Step (b) may be optional. Step (c) may include oxidative and / or non-oxidative alkene cleavage, via at least one of, but not limited to, the following group: dihydroxylation, RuCL mediated methods, oxone mediated methods, periodate mediated methods, and Grubbs alkene metathesis.

[0112] Step (c) may take place via at least two different synthetic routes namely Step (cl) and Step (c2). Both Step (cl) and Step (c2) may be employed in the method according to the disclosure. Alternatively, only one of Step (cl) or Step (c2) may be employed in the method according to the disclosure.

[0113] Step (cl) includes reacting the aldehydes together with DMAA, Rh(COD)OMe, 3MeOBzOH, xanthphos and toluene. Typically, Step (cl) takes place between 80°C to 100 °C and for a period of time between 10 minutes and 24 hours. Preferred example embodiments of this step are shown herein below.

[0114] Step (cl) provides for unsaturated alkylated hydrocarbons. Typically, the unsaturated alkylated hydrocarbons are alkenes.

[0115] The Applicant envisages additional and / or alternative synthetic strategies, including but not limited to, contacting / reacting / exposing CNSL derived / based alcohols, aldehydes and / or carboxylic acids to palladium and / or iridium catalysts.

[0116] Further, the Applicant envisages another synthetic strategy including conducting a functional group interconversion reaction to a leaving group, base mediated E2 elimination to obtain an alkene, and cleavage of the alkene.

[0117] Further, the Applicant envisages another synthetic strategy including direct dehydration of aldehyde derived hydroxyl using acids including but not limited to p-toluene sulfonic acid and / or propanephosphonic acid anhydride.

[0118] Still further, the Applicant envisages another synthetic strategy including condensing a CNSL aldehyde with malonic acid under basic conditions to undergo decarboxylation and alkene isomerization therein providing precursor compounds in accordance with this disclosure.

[0119] Step (c) may be optional.

[0120] There is further provided that the unsaturated alkylated hydrocarbons are alkenes and may further undergo hydrogenation to provide saturated alkylated hydrocarbons. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0121] There is further provided that the unsaturated alkylated hydrocarbons are alkenes and may further undergo ozonolysis and defunctionalisation (including decarboxylation) in order to reduce the alkyl chain length. It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below. Step (c2) includes reacting the aldehydes together with [Ir(COD)2Cl]2, PPh ,. 2MeTHF. Typically, Step (c2) takes place between 80°C to 150 °C and for a period of time between 10 minutes and 180 minutes. Preferred example embodiments of this step are shown herein below. Step (c2) may alternatively and / or additionally include conducting exposing the CNSL aldehydes to Pd / C (palladium on carbon catalyst) followed by hydrogenation. The Applicant envisages other carbon carbon cleavage reactions, preferably metal catalysed, conducted on any of CNSL derived / based alcohols, aldehydes and / or carboxylic acids, to provide saturated linear alkanes.

[0122] Step (c2) provides for saturated alkylated hydrocarbons.

[0123] The cannabinoids and / or precursors of cannabinoids and / or derivatives thereof according to the method may include 5-heptylbenzene-l,3-diol and / or 5-pentylbenzene-l,3-diol.

[0124] Typically, the precursor compounds many include, but not limited to, 5 -pentylresorcinol and / or 5- heptylresorcinol, both which may be used for downstream processing in the manufacturing of cannabinoids including tetrahydrocannabinol (THC) and tetrahydrocannabiphorol (THCP), respectively.

[0125] It is to be understood that further downstream processing is envisioned. The Applicant provides non limiting example embodiments of such further downstream processing herein below.

[0126] NON-LIMITING EXAMPLES:

[0127] Vacuum distillation of crude technical grade CNSL:

[0128] Crude technical grade cashew nut shell liquid (ca. 100g) obtained from Soxhlet extraction of cashew nut shell waste or by mechainical pressing was vacuum distilled (ca. lOmmHg) with concomitant decarboxylation of the anacardic acids at 180-200°C to provide CNSL (82 g) containing cardanols (ca. 90%) and cardols (ca. 10%).

[0129] Figure 1 shows reaction schemes for obtaining cardanols and cardols from crude cashew nut shell liquid (CNSL).

[0130] Acetylation of CNSL:

[0131] Method A: To distilled CNSL mixture (20.00g, ca.63.1mmol) in a 50 mL capacity sealed tube was added pivalic anhydride (13.00g, 69.8mmol), followed by triethylamine (10.12g, 100 mmol) under an inert atmosphere of argon gas. The resultant solution was stirred and heated to 100-110°C for 2h, after which time TLC (thin layer chromatography) analysis confirmed the reaction to be complete. Then, the reaction was poured into 200mL saturated aqueous NaHCCF and stirred for 30 min. at room temperature. The resultant biphasic mixture was then extracted into hexane (3 x 100mL), and the combined organic extracts were washed with a saturated solution of NaHCCF (lOOmL), water (lOOmL), followed by IM aqueous HC1 solution (lOOmL). The organic phase was then dried over MgSCL, and volatiles removed in-vacuo to provide the acetylated product mixture (25.6 g, ca. 63 mmol, quant.) as a pale yellow oil. Figure 2 show shows the acetylation of CNSL as described above.

[0132] Ozonolysis reactions

[0133] Ozonolysis of acetylated CNSL mixture:

[0134] To a solution of acetylated CNSL mixture (12.31g, ca. 30.9 mmol) in acetone (300 mL) was added distilled water (30 mL). The solution was cooled in an ice-bath as ozone gas was passed through the solution for 40 min until the reaction was complete as determined by TLC monitoring. The solution was then degassed by passing oxygen through the reaction for 2 min, followed by argon, for a further 5 min. Then, the solution was stirred, maintaining ice-bath cooling, as dimethyl sulphide (20 mL, 16.8g, 0.27 mol) was added by syringe. The mixture was stirred overnight at room temperature, after which time NMR analysis showed residual secondary ozonide (characteristic multiplet 5.3-5.19ppm). Thus, the solution was heated to reflux (bath temperature 60°C) for 3h, until complete by NMR analysis. The solvent was removed in-vacuo until a biphasic mixture of the product and residual water remained. Heptane (100 mL) was added, followed by a saturated solution of NaHC'CL (lOOmL)1, and the phases were shaken and separated. The aqueous phase was re-extracted with heptane (2 x 50mL), and the combined organics were washed again with a saturated solution of NaHCCL (lOOmL) followed by water (lOOmL). The combined extracts were dried over MgSCL, and the volatiles removed in-vacuo to provide the product aldehyde mixture (10.10 g, 32.2 mmol, ca. 104% yield2) as colourless oil with a distinct nutty aroma. The material was used without subsequent purification.

[0135] 1note: a small quantity of brine was needed to break emulsion during initial washings.

[0136] 2Material contains residual non-volatile heptaldehyde and malondialdehyde as byproducts.

[0137] 'H NMR (400 MHz, CDC13) 5 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, OH), 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).

[0138] 13C NMR (101 MHz, CDCI3) 5 202.93, 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.

[0139] The ozonolysis of acetylated CNSL is shown in Figure 3.

[0140] Ozonolysis of terminally unsaturated CNSL mixture:

[0141] To a solution of terminally unsaturated CNSL mixture (see reaction below for preparation of starting material) (0.710 g, ca. 2.50 mmol) in acetone (100 mL) was added distilled water (10 mL). The solution was cooled in an ice-bath as ozone gas was passed through the solution for 20 min until the reaction was complete as determined by TLC monitoring. The solution was then degassed by passing oxygen through the reaction for 2 min, followed by argon, for a further 5 min. Then, the solution was stirred, maintaining ice-bath cooling, as dimethyl sulphide (10 mL, 8.40 g, 0. 14 mol) was added by syringe. The mixture was stirred overnight at room temperature, after which time NMR analysis showed residual secondary ozonide (characteristic multiplet 5.3- 5.19ppm). Thus, the solution was heated to reflux (bath temperature 60°C) for 3h, until complete by NMR analysis. The solvent was removed in-vacuo until a biphasic mixture of the product and residual water remained. Heptane (100 mb) was added, followed by a saturated solution of NaHCCT (lOOmL)1, and the phases were shaken and separated. The aqueous phase was re-extracted with heptane (2 x 50mL), and the combined organics were washed again with a saturated solution of NaHCCT (lOOmL)1, followed by water (lOOmL). The combined extracts were dried over MgSCL. and the volatiles removed in-vacuo to provide the product aldehyde mixture (0.697 g, ca. 2.43mmol, ca. 97% yield) as a colourless oil. The material was used without subsequent purification.

[0142] Figure 4 shows ozonolysis of terminally unsaturated CNSL.

[0143] 'H NMR (300 MHz, CDCL) 5 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, OH), 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).

[0144] 13C NMR (75 MHz, CDC13) 5202.65, 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.

[0145] Decarbonylation of CNSL aldehydes to saturated alkanes:

[0146] Heptyl alkane mixture:

[0147] To the crude CNSL aldehyde mixture (1.22 g, ca. 3.88 mmol) was added heptane (10 mL) and the solution was stirred under an argon atmosphere for 5 min. Then, palladium on carbon (10% Wt, 0.212 g, 0.2 mmol, 5 mol%) was added and the reaction was heated to reflux for 24 h, at which point1H NMR analysis showed the reaction was complete. After cooling to room temperature, ethanol (20mL) was added and the reaction was hydrogenated at room temperature under an atmosphere of hydrogen gas (1 atm.) for 16h. Then, the reaction was filtered over celite, washed with ethanol (3 x 20 mL) and the combined filtrate was stripped of solvent in- vacuo to provide the crude product, which was taken up into heptane (50mL), washed with a saturated aqueous solution of NaHCCh (50 mL), and the aqueous phase re-extracted with heptane (2 x 20mL). The combined organic phases were then washed with water (50mL), dried over MgSCL, and the solvent removed in-vacuo to provide the crude product mixture as a colourless oil (1.03 g, ca, 3.60 mmol, ca. 97% yield*) *Approximate yield determined over two steps from acetylated CNSL mixture.

[0148] Figure 5 shows decarbonylation of heptaoctyl CNSL aldehydes to saturated alkanes.

[0149] 'H NMR (300 MHz, CDCI3) 5 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, OH), 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).

[0150] 13C NMR (75 MHz, CDCI3) 5 177.08, 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. Pentyl alkane mixture:

[0151] To the crude CNSL aldehyde mixture (0.510 g, ca. 1.78 mmol) was added heptane (10 mL) and the solution was stirred under an argon atmosphere for 5 min. Then, palladium on carbon (10% Wt, 0.110 g, 0.1 mmol, ca. 5 mol%) was added and the reaction was heated to reflux for 24 h, at which pointXH NMR analysis showed the reaction was complete. After cooling to room temperature, ethanol (20mL) was added and the reaction was hydrogenated at room temperature under an atmosphere of hydrogen gas (1 atm.) for 16h. The reaction was then filtered over celite, washed with ethanol (2 x 20 mL) and the combined filtrate was stripped of solvent in-vacuo to provide the crude product as a colourless oil which was taken up into heptane (20 ml) and washed with a saturated aqueous solution of NaHCCL. The aqueous phase was re-extracted with heptane (2 x 10 mL), and the combined organics were washed with water, dried over MgSCL, and the solvent was removed in-vacuo to provide the crude product (0.451g, ca. 1.75 mmol, ca. 98% yield*) as a colourless oil, which was used without subsequent purification. *Approximate yield determined over four steps from acetylated CNSL mixture.

[0152] Figure 6 shows decarbonylation of pentahexyl CNSL aldehydes to saturated alkanes

[0153] 'H NMR (400 MHz, CDC13) 5 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, OH), 6.60 (t, J= 2.0 Hz, OH), 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).

[0154] 13C NMR (101 MHz, CDC13) 5 177.16, 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.

[0155] Retro-hydroformylation of aldehyde mixture:

[0156] Method adapted from literature (J. Am. Chem. Soc. 2018, 140, 32, 10126-10130):

[0157] To a 50 mL capacity sealed tube that had been flushed with argon gas was added [Rh(COD)OMe]2 (19.0 mg, 0.040 mmol), xantphos (46.0 mg, 0.008 mmol), 3- methoxybenzoic acid (12.0 mg, 0.008 mmol) and toluene (4.0 mL). After stirring for 3 min, A. A-dimcthylacryla idc (630 pL, 600 mg, 6.0 mmol) and aldehyde mixture (0.608 g ca. 1.90 mmol) were added successively. The vial was sealed and the reaction mixture was stirred at 90 °C for 24 h. The solvent was then removed in-vacuo and the residue was taken up into heptane (lOOmL). The heterogeneous suspension was then fdtered, washed with heptane (2 x 10 mL) and the combined organics were washed with water (2 x lOOmL), and then with a saturated aqueous solution of NaHCCL (100 mL). The combined aqueous washings were re-extracted with heptane (2 x 50 mL), washed with water (50mL) and then dried over MgSCfi and directly fdtered over a pad of silica gel (ca, 20g). The silica pad was then washed with a solution of EtO Ac: hexane (2: 10) , (2 x 50mL), and the solvent removed in-vacuo to provide the product (0.512 g, ca. 1.80 mmol, ca. 99%*) as a pale yellow oil. * Approximate yield determined over two steps from acetylated CNSL mixture. NMR showed material contained ca. 90% desired terminally unsaturated product in combination with ca. 7% fully saturated decarbonylated product as well as ca. 3% internally unsaturated by-products.

[0158] Figure 7 shows the retro-hydroformylation of aldehyde mixture

[0159] 'H NMR (300 MHz, CDC13) 5 7.29 (s, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.94 - 6.81 (m, 2H), 6.79 - 6.64 (m, OH), 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, OH).

[0160] 13C NMR (75 MHz, CDC13) 5 177.11, 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.

[0161] One pot molecular homogenization:

[0162] 5-heptylbenzene-l,3-diol (also called 5-heptylresorcinol, sphaerophorol, spherophorol):

[0163] To a 50 mb capacity sealed tube that had been flushed with argon gas was added [Ir(OMe)(l,5-COD)]2 (51.2 mg, 0.079 mmol, ca. 1 mol%), Bis(pinacolato)diboron (2.170 g, 8.55 mmol, 1.15 eq.), followed by 4,4'- Di-tert-butyl-2,2'-dipyridyl (43.1 mg, 0.16 mmol, 2 mol%). The solids were stirred as the tube was flushed with Argon gas for 5 minutes, and the above mentioned product (2.11 g, ca. 7.37 mmol) was added by pipette, using hexane (2 x 0.5mL) to rinse the pipette and ensure complete transfer of material into the reaction vessel. The tube was then flushed with argon gas for a further minute, and then sealed and heated, with stirring, to 110°C for 2h, after which time NMR analysis showed the reaction was complete. The tube was then cooled in an ice-bath, and ethanol (10 mb) was added slowly portion-wise. The ice bath was removed, and the solution was transferred into a 250mL flask, rinsing with ethanol (2 x 20mL) to ensure complete transfer. Then, a freshly prepared solution of urea hydrogen peroxide (2.48 g, 26.4 mmol) in ethanol (100 mb) was added slowly, drop-wise, over a period of 1 hour. After this time, NMR analysis confirmed the reaction was complete, and 20 mb of a saturated aqueous sodium thiosulfate solution was added and the mixture was stirred for 5 min, after which time 50 mb of a 10% Wt. aqueous NaOH solution was added, and the resultant solution was stirred for 2 hours at room temperature, until complete by NMR analysis. Then, the solution was acidified to pH <3 with a IM aqueous HC1 solution, causing the colour to change from deep red to pale yellow. The mixture was the extracted into ethyl acetate (3 x 50 mb), and the combined extracts were washed with water (lOOmL) and then with an aqueous saturated NaHCCF solution (100 mb), followed by brine (lOOmL). The organic phase was then dried over MgSCL. and solvent removed in-vacuo to provide the crude product, which was chromatographed using a 0-30% (EtOAc: Hexane) gradient elution to provide the product 5-heptylbenzene- 1 ,3-diol (1.23 g, 5.91 mmol, 83% yield from CNSL*) as an amber oil which crystalized upon standing at room temperature.

[0164] *Yield calculated from earliest known pure precursor (Starting CNSL mixture)

[0165] Figure 8 shows one pot molecular homogenization to provide 5-heptylbenzene-l,3-diol. 'H NMR (300 MHz, CDC13) 5 6.24 (d, J= 1.7 Hz, 2H), 6.18 (t, J= 2.2 Hz, 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).

[0166] 13C NMR (75 MHz, CDC13) 5 156.55, 146.17, 108.04, 100.13, 35.82, 31.80, 31.06, 29.24, 29.16, 22.66, 14.10.

[0167] 5-pentylbenzene-l,3-diol (also called olivetol or 5-pentylresorcinol):

[0168] To a 50 mL capacity sealed tube that had been flushed with argon gas was added [Ir(OMe)(l,5-cod)]2 (9.7 mg, 0.015mmol, 1.5 mol%). bis(pinacolato)diboron (412 mg, 1.62mmol, 1 eq.), followed by 4,4'-di-tert- butyl-2,2'-dipyridyl (8.1 mg, 0.030mmol, 2 mol%) and the above mentioned product (250 mg, ca. 0.970 mmol.) The tube was then flushed with argon gas for a further minute, and 0.5mL hexane was added to improve mixing. The tube was then sealed and heated, with stirring, to 110°C for 2h, after which time NMR analysis showed the reaction was complete. The tube was then cooled in an ice-bath, and ethanol (10 mL) was added slowly portion-wise. The ice bath was removed, and a freshly prepared solution of urea hydrogen peroxide (470mg, 5 mmol) in ethanol (30 mL) was added slowly, dropwise, over a period of 2 hours. After this time, NMR analysis confirmed the reaction was complete, and 2 mL of a saturated sodium thiosulfate solution was added and the mixture was stirred for 5 min, after which time the contents of the reaction flask were poured into a conical flask containing 40 mL of a IM aqueous NaOH solution, and the resultant solution was stirred for 1 hour at room temperature. Then, the solution was acidified to pH <3 with a IM aqueous HC1 solution, causing the colour to change from deep red to pale yellow. The mixture was the extracted into ethyl acetate (3 x 50 mL), and the combined extracts were washed twice with IM aqueous HC1 solution (lOOmL), and then with an aqueous saturated NaHCCL solution (100 mL), followed by brine (lOOmL). The organic phase was then dried over MgSCL, and solvent removed in-vacuo to provide the crude product, which was chromatographed using a 0-30% (EtOAc: Hexane) gradient elution to provide 5-pentylbenzene-l,3-diol (0. 112 mg, 0.621mmol, 62% yield from CNSL*) as a pale yellow oil which crystalized upon protracted standing at room temperature. *Yield calculated from earliest known pure precursor (Starting CNSL mixture)

[0169] Figure 9 shows one pot molecular homogenization to provide 5-pentylbenzene-l,3-diol.

[0170] 'H NMR (400 MHz, CDC13) 5 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).

[0171] While the subject matter of the disclosure, including aspects one to six, has been described in detail with respect to specific embodiments and / or examples thereof, including various methods, compounds and / or formulations manufactured in according to said methods and / or the compounds and / or formulations themselves, it will be appreciated that those skilled in the art, upon attaining an understanding of the foregoing may readily conceive of alterations to, variations of and equivalents to these embodiments. Accordingly, the scope of the present disclosure should be assessed as that of the claims and any equivalents thereto, which claims are appended hereto.

Claims

AMENDED CLAIMS received by the International Bureau on 17 July 2025 (17.07.2025)CLAIMS:

1. A method of manufacturing cannabinoids and / or precursors of cannabinoids and / or derivatives thereof from cashew nut shell liquid (CNSL), the CNSL including anacardic acids, cardanols, and cardols, the method comprising the following steps:(a). decarboxylation of the anacardic acids to provide synthetic cardanols;(b). protection of the cardols and synthetic cardanols providing a protected cardols and protected cardanols, including protection by way of acetylation of the cardols and synthetic cardanols providing acetylated cardols and acetylated cardanols;(c). cleaving alkene bonds of acetylated cardols and acetylated cardanols, wherein cleavage may provide CNSL aldehydes, including in an embodiment by way of ozonolysis of acetylated cardols and acetylated cardanols to provide CNSL aldehydes; and(d). defunctionalization of the CNSL aldehydes, including decarbonylation of the CNSL aldehydes to provide saturated or unsaturated alkylated CNSL hydrocarbons.

2. The method of Claim 1, wherein Step (b) includes protection utilizing at least one of the following protecting functional groups consisting of: mesylate, tosylates and acetals.

3. The method of Claiml or Claim 2, wherein Step (c) includes oxidative and / or non-oxidative alkene cleavage via at least one of to the following group consisting of: dihydroxylation, RuC13 mediated methods, oxone mediated methods, periodate mediated methods, and Grubbs alkene metathesis.

4. The method of any one of Claims 1 to 3, wherein Step (d) takes place via synthetic route Step (dl), wherein Step (dl) includes reacting the CNSL aldehydes together with DMAA, Rh(COD)OMe, 3MeOBzOH, xanthphos and toluene.

5. The method of Claim 4, wherein Step (dl) takes place between 80°Cto 100 °C and for a period of time between 10 minutes and 24 hours.

6. The method of any one of Claims 1 to 3, wherein Step (d) takes place via synthetic route Step (d2), wherein Step (d2) includes reacting the CNSL aldehydes together with [Ir(coe)2Cl]2, PPhs, 2MeTHF.

7. The method of Claim 6, wherein Step (d2) takes place between 80°Cto 150 °C and for a period of time between 10 minutes and 180 minutes.

8. The method of Claim 6 or Claim 7, wherein Step (d2) includes conducting or exposing the CNSL aldehydes to Pd / C (palladium on carbon catalyst) followed by hydrogenation.

239. The method of any one of Claims 1 to 8, wherein the unsaturated alkylated CNSL hydrocarbons are alkenes and further undergo hydrogenation to provide saturated alkylated CNSL hydrocarbons.

10. The method of any one of Claims 1 to 8, wherein the unsaturated alkylated CNSL hydrocarbons are alkenes and further undergo ozonolysis and defunctionalization (including decarboxylation) to reduce alkyl chain length.

11. The method of any one of Claims 1 to 10, wherein the precursors of cannabinoids comprise 5 -heptylbenzene- 1,3 -diol and / or 5-pentylbenzene-l,3-diol.

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

13. A method of manufacturing cannabinoids and / or precursors of cannabinoids and / or derivatives thereof, the method comprising the following steps:(a). protection of a cardol and / or a cardanol providing a protected cardol and / or a protected cardanol, including protection by way of acetylation of the cardol and / or cardanol providing acetylated cardol and acetylated cardanols;(b). cleaving alkene bonds of acetylated cardol and acetylated cardanols, wherein cleavage provides aldehydes, including in an embodiment by way of ozonolysis of acetylated cardol and acetylated cardanols to provide aldehydes;(c). defunctionalization of the aldehydes, including decarbonylation of the aldehydes to provide saturated or unsaturated alkylated hydrocarbons.

14. The method of Claim 14, wherein at least one of the cardol and / or cardanols are from cashew nut shell liquid (CNSL).

15. The method of Claim 13 or Claim 14, wherein Step (a) includes protection utilizing at least one of the following protecting functional groups consisting of: mesylate, tosylates and acetals.

16. The method of any one of Claims 13 to 15, wherein Step (c) includes oxidative and / or non- oxidative alkene cleavage via at least one of to the following group consisting of: dihydroxylation, RuCL mediated methods, oxone mediated methods, periodate mediated methods, and Grubbs alkene metathesis.

17. The method of any one of Claims 13 to 16, wherein Step (c) takes place via synthetic route Step (cl), wherein Step (cl) includes reacting the CNSL aldehydes together with DMAA, Rh(COD)OMe, 3MeOBzOH, xanthphos and toluene.

18. The method of Claim 17, wherein Step (cl) takes place between 80°C to 100 °C and for a period of time between 10 minutes and 24 hours.

19. The method of any one of Claims 13 to 16, wherein Step (c) takes place via synthetic route Step (c2), wherein Step (c2) includes reacting the CNSL aldehydes together with [Ir(coe)2Cl]2, PPhs, 2MeTHF.

20. The method of Claim 19, wherein Step (c2) takes place between 80°C to 150 °C and for a period of time between 10 minutes and 180 minutes.

21. The method of Claim 19 or Claim 20, wherein Step (c2) includes conducting or exposing the CNSL aldehydes to Pd / C (palladium on carbon catalyst) followed by hydrogenation.

22. The method of any one of Claims 13 to 21, wherein the unsaturated alkylated CNSL hydrocarbons are alkenes and further undergo hydrogenation to provide saturated alkylated CNSL hydrocarbons.

23. The method of any one of Claims 13 to 21, wherein the unsaturated alkylated CNSL hydrocarbons are alkenes and further undergo ozonolysis and defunctionalization (including decarboxylation) to reduce alkyl chain length.

24. The method of any one of Claims 13 to 23, wherein the precursors of cannabinoids comprise 5 -heptylbenzene- 1,3 -diol and / or 5-pentylbenzene-l,3-diol.

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

26. A method of manufacturing precursor compounds for manufacturing cannabinoids and / or methods of manufacturing cannabinoids, the method including use of an anacardic acid and / or a cardanol and / or a cardol and / or an arene and / or a symmetrical resorcinol, wherein at least one of the anacardic acid and / or the cardanol and / or the cardol and / or the arene and / or the symmetrical resorcinol are derived from cashew nut shell liquid (CNSL) and / or a chemical component thereof.

27. The method of Claim 26, wherein the precursor compounds comprise 5 -pentylresorcinol and / or 5-heptylresorcinol.

28. The method of Claim 27, wherein 5 -pentylresorcinol is used for downstream processing in the manufacturing of the cannabinoid tetrahydrocannabinol (THC) and / or wherein 5 -heptylresorcinol is used for downstream processing in the manufacturing of the cannabinoid tetrahydrocannabiphorol (THCP).26