Allyl-derivatives of cannabinoids

Abstract

The disclosure relates to derivatives as well as production-processes of allyl-derivatives of cannabinoids. Also disclosed are medical uses of said derivatives.

Description

[0001] TR0011P-WO2 Allyl-derivatives of cannabinoids The disclosure relates to derivatives as well as production-processes of allyl-derivatives of can- nabinoids. Also disclosed are medical uses of said derivatives. Background of the Disclosure 5 Cannabinoids are terpene phenols found in flowering Cannabinaceae plants of the genus Can- nabis, namely in the species Cannabis sativa, Cannabis indica, and Cannabis ruderalis and are subdivided into 12 classes: cannabigerols (CBG), cannabichromenes (CBC), cannabidiols (CBD), cannabinodiols (CBND), tetrahydrocannabinols (THC), cannabinols (CBN), cannabitriols (CBT), cannabielsoins (CBE), isocannabinoids, cannabicyclols (CBL), cannabicitrans (CBT) and 10 cannabichromanones (CBCN). Cannabinoids have found wide applications, mainly in the medical field, as food additives and for cosmetic use. For example, cannabidiol has been proposed for the treatment of anxiety, ad- diction, psychosis, movement disorders, and pain (Kirkland et al., Psychiatry Research.308: 114347, 2022; Black et al., The Lancet. Psychiatry.6 (12): 995–1010, 2019; VanDolah et al., 15 Mayo Clinic Proceedings.94 (9): 1840–1851, 2019; Prud'homme et al., Substance Abuse.9: 33–38, 2015). Distinct physiological effects are caused by binding of the cannabinoids to the cannabinoid receptors CB1 and CB2 of the endocannabinoid system. Both CBD and Δ9-THC are used as pharmaceuticals for modulating appetite, pain, mood and memory (effected at the CB1 receptor) and for influencing the immune system (effected at the20 CB2 receptor). However, the psychoactive, intoxicating effect is not preferred when THC-deriva- tives are used in therapeutic settings. Accordingly, there is a need for novel THC-derivatives, which possess only mild or ideally no psychoactive and intoxicating effects, while providing and / or retaining one or more of the wanted beneficial effects facilitated by binding to the CB1- receptor and / or the CB2-receptor. 25 Currently known THC-derivatives display a mixed effect spectrum comprising both wanted and unwanted physiological effects. Accordingly, there is also a need for THC-derivatives which es- sentially display a single or main effect, also referred to as mono-therapeutic compounds. The above-mentioned problems are solved by the subject-matter described here below. June 25, 2025 1 / 74 TR0011P-WO2 y of the invention A first aspect of this disclosure relates to a compound according to Formula I 5 wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, 10 c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and 15 h) wherein R1and R2together form a ring structure selected from the group consisting of , June 25, 2025 2 / 74 TR0011P-WO2 i) R1is (C=O)OCH3and R2is allyl, wherein R3is selected from propyl, pentyl, heptyl, This disclosure thus provides synthetic access to hitherto unknown C-allyl-Δ9-tetrahydrocanna- binol derivatives (C-allyl-Δ9-THC), C-allyl-Δ8-tetrahydrocannabinol derivatives (C-allyl-Δ8-THC), 5 C-allyl-hexahydrocannabinol derivatives (C-allyl-HHC), as well as C-allyl-cannabinol derivatives (C-allyl-CBN). Disclosed are also the respective intermediate compounds, i.e. O-allyl-deriva- tives, which are used to achieve the final C-allyl derivatives by Claisen rearrangement. The disclosed compounds are derivatives with reduced or absent psychoactive, intoxicating ef- fects. The compound according to Formula I is stable and suitable for shipping and storage pur- 10 poses for extended periods of time and in the absence of refrigeration conditions. It shall be understood that the compound according to Formula I has two chiral C-atoms (at the 6a and 10a positions), provided that the ring A is selected from . If the ring A is aromatic, the indicated chiral centers will disappear, and there will be no H atoms at the 6a and 10a positions. 15 A second aspect of the disclosure relates to a process for the synthesis of the compounds i) to viii), the compounds i) to viii) being i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN); ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); iii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- 20 benzo[c]chromene (O-Allyl-^8-THC); iv) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen- 1-ol (C-Allyl-^8-THC); v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen (O-Allyl-^9-THC); 25 vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen- June 25, 2025 3 / 74 TR0011P-WO2 1-ol (C-Allyl-^9-THC); vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromene (O-Allyl-HHC); or viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 5 benzo[c]chromen-1-ol (C-Allyl-HHC), the process comprising the steps of: a. Providing a starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN, and dissolving the starting compound in a solvent; b. Reacting the starting compound with allyl-bromide to obtain an intermediate product; 10 c. Extracting the intermediate product; d. Washing and drying the intermediate product; e. Optionally heating the intermediate product; f. Optionally obtaining a second product; and g. Optionally isolating the second product. 15 In a third aspect this disclosure relates to a pharmaceutical composition comprising the com- pounds according to this disclosure. In a fourth aspect, this disclosure relates to compounds according to this disclosure for use in medicine, or the pharmaceutical composition according to this disclosure for use in medicine. In a fifth aspect this disclosure relates to compounds according to this disclosure for use in the 20 treatment of a condition selected from the group consisting of psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxiety disorder and / or depression, neurological disor- ders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, Inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nau- sea and / or vomiting, and combinations thereof. 25 In a related aspect this disclosure relates to the pharmaceutical composition according to this disclosure for use in the treatment of a condition selected from the group consisting of psychiat- ric disorders, such as post-traumatic stress disorder (PTSD), anxiety disorder and / or depres- sion, neurological disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, June 25, 2025 4 / 74 TR0011P-WO2 Inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nausea and / or vomiting, and combinations thereof. In a sixth aspect this disclosure relates to a kit comprising the compounds according to this dis- closure, or the pharmaceutical composition according to this disclosure, further comprising at 5 least one object selected from the group consisting of an applicator, a package leaflet, a trans- dermal patch, a second active agent, and a treatment schedule, as well as combinations thereof. In a further aspect this disclosure relates to a compound according to Formula XX 10 XX, wherein R1= methyl, ethyl, or propyl; wherein R2= methyl, ethyl, or propyl; wherein R3= propyl, pentyl, or heptyl. This disclosure thus provides synthetic access to hitherto unknown O-allyl-cannabidiol deriva- 15 tives. In summary, this disclosure provides synthetic access to hitherto unknown cannabinoids, with- out the requirement of chromatographic steps for purification. Whereas in the art, providing chemically pure cannabinoids typically requires cumbersome and resource-intensive chromato- graphic purification. June 25, 2025 5 / 74 TR0011P-WO2 Detailed description Compounds A first aspect of this disclosure relates to a compound according to Formula I 5 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, 10 b) R1is H and R2is allyl, c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, 15 g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of June 25, 2025 6 / 74 TR0011P-WO2 , i) R1is (C=O)OCH3 and R2is allyl, wherein R3is selected from propyl, pentyl, heptyl, In an alternative aspect this disclosure relates to a compound according to Formula I 5 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to i): 10 a) R1is allyl and R2is H, b) R1is H and R2is allyl, c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, 15 f) R1is H and R2is propionyl acid, June 25, 2025 7 / 74 TR0011P-WO2 g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of , i) R1is (C=O)OCH3 and R2is allyl, 5 wherein R3is selected from propyl, pentyl, heptyl, , or alternatively wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options c) to i): c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, 10 d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of 15 , i) R1is (C=O)OCH3and R2is allyl, June 25, 2025 8 / 74 TR0011P-WO2 wherein R3is selected from propyl, pentyl, heptyl, In one embodiment, this disclosure relates to a compound according to Formula I 5 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to b): a) R1is allyl and R2is H, 10 b) R1is H and R2is allyl, wherein R3is selected from propyl, pentyl, heptyl, In one embodiment, this disclosure relates to a compound according to Formula I June 25, 2025 9 / 74 TR0011P-WO2 wherein R1and R2are chosen in combination according to any one of the following options a) to 5 b): a) R1is allyl and R2is H, b) R1is H and R2is allyl, wherein R3is selected from propyl, pentyl, heptyl, 10 wherein R1and R2are chosen in combination according to any one of the following options a) to b): a) R1is allyl and R2is H, b) R1is H and R2is allyl, wherein R3is selected from propyl, heptyl, June 25, 2025 10 / 74 TR0011P-WO2 In one embodiment, this disclosure relates to a compound according to Formula I I 5wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, 10 c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and 15 h) wherein R1and R2together form a ring structure selected from the group consisting of , i) R1is (C=O)OCH3and R2is allyl, June 25, 2025 11 / 74 TR0011P-WO2 wherein R3is pentyl. In one embodiment, this disclosure relates to a compound according to Formula I I 5wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, 10 c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and 15 h) wherein R1and R2together form a ring structure selected from the group consisting of , i) R1is (C=O)OCH3and R2is allyl, June 25, 2025 12 / 74 TR0011P-WO2 wherein R3is pentyl. In one embodiment, this disclosure relates to a compound according to Formula I I 5wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options c) to i): c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, 10 e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of , 15 i) R1is (C=O)OCH3and R2is allyl, wherein R3is pentyl. In one embodiment, a compound is provided being either June 25, 2025 13 / 74 TR0011P-WO2 i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN); ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); iii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- benzo[c]chromene (O-Allyl-^8-THC); 5 iv) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1- ol (C-Allyl-^8-THC); v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen (O-Allyl-^9-THC); vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol 10 (C-Allyl-^9-THC); vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromene (O-Allyl-HHC); or viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromen-1-ol (C-Allyl-HHC). 15 In one embodiment, a compound is provided being either i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN); ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen (O-Allyl-^9-THC); 20 vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C-Allyl-^9-THC); vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromene (O-Allyl-HHC); or viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 25 benzo[c]chromen-1-ol (C-Allyl-HHC). In one embodiment, a compound is provided being either June 25, 2025 14 / 74 TR0011P-WO2 ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C-Allyl-^9-THC); viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 5 benzo[c]chromen-1-ol (C-Allyl-HHC). In one embodiment, a compound is provided being either (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C- Allyl-^9-THC); or (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-1- 10 ol (C-Allyl-HHC). In one embodiment, a compound is provided being either (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen (O- Allyl-^9-THC); or (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C- 15 Allyl-^9-THC); or (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromene (O-Allyl-HHC); or (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-1- ol (C-Allyl-HHC).In one embodiment, this disclosure provides a compound according to any one 20 of formula II to formula V: II June 25, 2025 15 / 74 TR0011P-WO2 5 In one embodiment, this disclosure provides a compound according to formula II, formula III or formula V: June 25, 2025 16 / 74 TR0011P-WO2 II 5 V. In one embodiment, this disclosure provides a compound according to formula II or formula V: June 25, 2025 17 / 74 TR0011P-WO2 . In one embodiment, this disclosure provides a compound according to formula III: 5 In one embodiment, the compound may be selected from the group consisting of the ∆8-THC- or ∆9-THC-derivatives of formula VI to XVI: 10 wherein R is selected from -H, -CH3, -CH2-CH3, or -CH=CH-CH3. 15 VII, June 25, 2025 18 / 74 

[0002] TR0011P-WO2 XV, and XVI. In one embodiment, the compound may be selected from the group consisting of the ∆8-THC- or 5 ∆9-THC-derivatives of formula VI to IX and XI to XVI: wherein R is selected from -CH3, -CH2-CH3, or -CH=CH-CH3. 10 15 June 25, 2025 21 / 74

[0003]

[0004] IIIA

[0005] ZZ TR0011P-WO2 XIII, 5 XVI. In a further aspect this disclosure relates to a compound according to Formula XX June 25, 2025 23 / 74 TR0011P-WO2 XX, wherein R1= methyl, ethyl, or propyl; wherein R2= methyl, ethyl, or propyl; 5 wherein R3= propyl, pentyl, or heptyl. In one embodiment, this disclosure provides a compound according to formula XXI XXI. In one embodiment, the compounds according to this disclosure are characterized by one or 10 more of the following features: a. having a reduced psychoactive effect as compared to ∆9-Tetrahydrocannabinol (∆9- THC); b. having an elevated effect selected from the group consisting of pain relief, appetite June 25, 2025 24 / 74 TR0011P-WO2 stimulation, anti-inflammatory properties, muscle relaxation, anxiety reduction, and antie- metic effect reduction, as well as combinations thereof, as compared to ∆9-Tetrahydro- cannabinol (∆9-THC); c. having an increased lipophilicity as compared to ∆9-Tetrahydrocannabinol (∆9-THC). 5 Process A second aspect of the disclosure relates to a process for the synthesis of the compounds i) to viii), the compounds i) to viii) being i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN); ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); 10 iii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- benzo[c]chromene (O-Allyl-^8-THC); iv) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen- 1-ol (C-Allyl-^8-THC); v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H- 15 benzo[c]chromen (O-Allyl-^9-THC); vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen- 1-ol (C-Allyl-^9-THC); vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromene (O-Allyl-HHC); or 20 viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromen-1-ol (C-Allyl-HHC), the process comprising the steps of: a. Providing a starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN, and dissolving the starting compound in a solvent; 25 b. Reacting the starting compound with allyl-bromide to obtain an intermediate product; c. Extracting the intermediate product; June 25, 2025 25 / 74 TR0011P-WO2 d. Washing and drying the intermediate product; e. Optionally heating the intermediate product; f. Optionally obtaining a second product; and g. Optionally isolating the second product. 5 In one embodiment, the process comprises the steps of: a. Providing a starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN, and dissolving the starting compound in a solvent to obtain a solution; b. Reacting the solution with allyl-bromide to obtain an intermediate product, wherein the reaction step b. is performed at a temperature range of 10 to 40 °C; 10 c. Extracting the intermediate product to obtain one or more extract portions, and combin- ing the one or more extract portions to obtain a combined extract; d. Washing and drying the combined extract, to obtain a washed and dried intermediate product; e. Optionally heating the washed and dried intermediate product; 15 f. Optionally obtaining a second product; and g. Optionally isolating the second product. In one embodiment, the process comprises the steps of: a. Providing a starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN, and dissolving the starting compound in a solvent to obtain a solution; 20 b. Reacting the solution with allyl-bromide to obtain an intermediate product; c. Extracting the intermediate product to obtain one or more extract portions, and combin- ing the one or more extract portions to obtain a combined extract; d. Washing and drying the combined extract, to obtain a washed and dried intermediate product; 25 e. Optionally heating the washed and dried intermediate product; June 25, 2025 26 / 74 TR0011P-WO2 f. Optionally obtaining a second product; and g. Optionally isolating the second product. Step b. realizes the manufacture of, respectively, the O-allyl-Δ9-THC-, the O-allyl-Δ8-THC-, the O-allyl-HHC, or the O-allyl-CBN derivative according to this disclosure, depending on the cho- 5 sen starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN in step a. Step f. realizes the manufacture of, respectively, the C-allyl-Δ9-THC-, the C-allyl- Δ8-THC-, the C-allyl-HHC, or the C-allyl-CBN derivative according to this disclosure, depending on the cho- sen starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN in step a. In one embodiment, providing a starting compound comprises providing the starting compound 10 in pure form, e.g., crystalline form, or in an amorphous form. In one embodiment, dissolving the starting compound in a solvent comprises choosing an appropriate polar, aprotic solvent which facilitates the subsequent reactions. In one embodiment, the solvent is chosen from the group of polar (hydrophilic) aprotic solvents, such as, e.g., DMF (dimethylformamide), DMSO (dimethyl sulfoxide), acetone, acetonitrile, dichloromethane, ethyl acetate, pyridine, sulfolane, and tetrahy- 15 drofuran (THF). If this disclosure refers to a step of "reacting" the starting compound or any other compound, as well as heating the intermediate product, with a chemical agent and / or under the influence of thermal energy, optionally in a suitable solvent, it shall be understood that each step or se- quence of steps is carried out for a time sufficient to effect (i.e. allow) the underlying reaction (to 20 take place) of at least a portion of the starting compound(s) into the target (or intermediate) compound. Preferably, the time is sufficient to allow the underlying reaction to take place and to reach chemical equilibrium between the starting compound(s) and the target (or intermediate) compounds at the respectively chosen reaction or treatment conditions. Analogously, the skilled person understands and knows how to carry out the addition of chemical (re)agents under e.g. 25 stirring and / or maintaining a preferred temperature to optimize and / or maximize the yields of the target compounds. Furthermore, the skilled person understands and knows how to carry out the work-up of reaction batches, e.g. adding water and / or combining with an aqueous HCl solution for neutralization purposes, extraction using organic solvents, washing steps with e.g. aqueous HCl solution or with saturated NaCl solution, drying over Na2SO4, filtration and concentration, to 30 optimize and / or maximize the yields of the target compounds. If this disclosure refers to a step of "extracting" the intermediate compound or any other com- pound, it shall be understood that with the aid of a suitable solvent, such as an extractant, one or more components are selectively extracted from a solution or a mixture of any kind. June 25, 2025 27 / 74 TR0011P-WO2 If this disclosure refers to a step of “washing” the intermediate compound or any other com- pound, it shall be understood that with the aid of a suitable washing reagent or solvent, possible impurities or contaminants are removed. In one embodiment, reacting the starting compound with allyl-bromide to obtain an intermediate 5 product comprises adding allyl-bromide to the dissolved starting compound, subsequently add- ing a chemical base under vigorous stirring of the solution of the starting compound and the al- lyl-bromide in the solvent. In one embodiment, the reaction step b. is performed at a tempera- ture range of 10 to 40 °C, preferably 15 to 35 °C, more preferably 20 to 30 °C, for 2 to 40 hours, preferably 5 to 30 hours, more preferably 10 to 20 hours. 10 In one embodiment, the chemical base is chosen from potassium carbonate or sodium car- bonate. In one embodiment the chemical base used is potassium tert-butoxide. Potassium tert- butoxide was found to be superior over potassium carbonate and afforded nearly complete con- version of the starting compound into the intermediate product. In one embodiment, extracting the intermediate product comprises adding water to the reaction 15 mixture and stirring the reaction mixture for 30 to 120 minutes at a temperature range of 10 to 40 °C, preferably 15 to 35 °C, more preferably 20 to 30 °C, and subsequently extracting the re- action mixture with an extraction solvent. Preferably, the reaction mixture is extracted with ex- traction solvent two to six times, preferably four times, to obtain extract portions. In one embodi- ment, the extraction solvent is chosen from dichloromethane, diethyl ether, or tetrahydrofuran 20 (THF). In one embodiment, washing and drying the intermediate product comprises combining the ex- tract portions, washing with saturated NaHCO3 solution and brine, drying over Na2SO4, subse- quent filtration of the extract portions, and concentration of the combined extract portions. In one embodiment, concentration of the combined extract portions comprises removal of the ex-25 traction solvent from the extract portions to obtain the intermediate product in pure, e.g., crystal- line, form, or as an oil. In one embodiment the step of heating the intermediate product, i.e., heating step e. may be performed under an inert gas atmosphere, chosen from, e.g., nitrogen (N2) or argon. The step of heating the intermediate product may be performed in the absence of a solvent. 30 In one embodiment the heating step e. is carried out at temperatures from 150 to 200 °C, or from 160 to 190 °C, or from 175 to 180 °C. In one embodiment the heating step e. is carried out for 4 to 10 h, or for 5 to 9 h, or for 5 to 8 h. In one embodiment the heating step e. is carried out under a N2 atmosphere at 160 to 190 °C for 5 to 8 h. In one embodiment the heating step e. is June 25, 2025 28 / 74 TR0011P-WO2 carried out in the presence of a Lewis acid catalyst, such as, e.g., boron trifluoride (BF₃), tita- nium tetrachloride (TiCl₄), or aluminum chloride (AlCl₃). In one embodiment the heating step e. is carried out to enable and / or facilitate a Claisen rearrangement. The Claisen rearrangement is an organic reaction named after the German chemist Rainer Lud- 5 wig Claisen. It involves the conversion of allyl vinyl ethers into γ,δ-unsaturated carbonyl com- pounds through a sigmatropic rearrangement. This rearrangement is typically initiated by heat- ing the allyl vinyl ether in the presence of a Lewis acid catalyst. In one embodiment the heating step e. is carried out to perform a Claisen-Ireland rearrange- ment of the intermediate compound to obtain structures wherein R1and R2together form a ring 10 structure selected from the group consisting of Step f. affords the compounds C-allyl-Δ9-THC-, C-allyl- Δ8-THC-, C-allyl-HHC, and C-allyl-CBN according to this disclosure, all of which have a hydroxyl group at the position 1 according to IU- PAC nomenclature. Said phenolic hydroxyl group lends itself for further derivatization and may 15 be reacted and thus functionalized to obtain a formate or a carbonate derivative. A related aspect of the disclosure relates to a process for the synthesis of the compounds XX, the process comprising the steps of: a. Providing a starting compound XX’, and dissolving the starting compound XX’ in a sol- vent; 20 June 25, 2025 29 / 74 TR0011P-WO2 XX’, wherein R1= methyl, ethyl, or propyl, wherein R2= methyl, ethyl, or propyl, and wherein R3= propyl, pentyl, or heptyl b. Reacting the starting compound XX’ with allyl-bromide to obtain an intermediate product; 5 c. Extracting the intermediate product; d. Washing and drying the intermediate product; e. Optionally heating the intermediate product; f. Optionally obtaining a second product; and g. Optionally isolating the second product. 10 In one embodiment, the process for the synthesis of the compounds XX comprises the steps of: a. Providing a starting compound XX’, and dissolving the starting compound XX’ in a sol- vent to obtain a solution; b. Reacting the solution with allyl-bromide to obtain an intermediate product; c. Extracting the intermediate product to obtain one or more extract portions, and combining 15 the one or more extract portions to obtain a combined extract; d. Washing and drying the combined extract, to obtain a washed and dried intermediate product; e. Optionally heating the washed and dried intermediate product; f. Optionally obtaining a second product; and 20 g. Optionally isolating the second product. Step b. realizes the manufacture of compounds XX. Step d. affords compounds XX in pure form. Step f. realizes the manufacture of the C-allyl derivates of compounds XX, optionally after a Claisen rearrangement. June 25, 2025 30 / 74 TR0011P-WO2 Pharmaceutical composition The compounds of the present disclosure may be formulated as a pharmaceutical composition for the administration selected from the group consisting of oral administration, sublingual ad- ministration, buccal administration, rectal administration, intravenous (IV) administration, intra- 5 muscular (IM) administration, subcutaneous (SC) administration, inhalative administration, transdermal administration, topical administration, intranasal administration and intraocular ad- ministration, as well as combinations thereof. In one aspect, this disclosure provides a pharmaceutical composition comprising a compound according to this disclosure. 10 In one aspect, the pharmaceutical composition further comprises - at least one excipient selected from the group consisting of fillers such as lactose, micro- crystalline cellulose, dicalcium phosphate, mannitol, starches, e.g., corn starch; - optionally a binder, e.g., starch paste, povidone (polyvinylpyrrolidone), hydroxypropyl cellu- lose, methylcellulose, carboxymethyl cellulose sodium; 15 - optionally a disintegrant, e.g., croscarmellose sodium, crospovidone, sodium starch glyco- late, crosslinked polyvinylpyrrolidone (PVP), microcrystalline cellulose; - optionally a glidant, e.g., magnesium stearate, talc, colloidal silicon dioxide, sodium stearyl fumarate, stearic acid; - optionally a coating, e.g., hydroxypropyl methylcellulose (HPMC), ethyl cellulose, shellac, 20 polyvinyl alcohol (PVA), gelatin; - optionally a preservative, e.g., benzalkonium chloride, methylparaben, propylparaben, sorbic acid, benzyl alcohol; - optionally a colorant, e.g., iron oxides, titanium dioxide, indigo carmine, sunset yellow, al- lura red; 25 - optionally a flavoring, e.g., aspartame, sucrose, sorbitol, sodium saccharin, peppermint oil; - optionally a solubilizer, e.g., polysorbate 80, propylene glycol, ethanol, cyclodextrins, poly- ethylene glycol (PEG); - optionally a buffer system, e.g., citric acid and sodium citrate, hydrogen phosphate and June 25, 2025 31 / 74 TR0011P-WO2 dihydrogen phosphate, acetic acid and sodium acetate. In one embodiment, the pharmaceutical composition comprises at least one excipient selected from the group consisting of fillers, such as lactose, microcrystalline cellulose, dicalcium phos- phate, mannitol, starches, e.g., corn starch. 5 In one embodiment, the pharmaceutical composition comprises a binder, e.g., starch paste, povidone (polyvinylpyrrolidone), hydroxypropyl cellulose, methylcellulose, and carboxymethyl cellulose sodium. In one embodiment, the pharmaceutical composition comprises a disintegrant, e.g., croscarmel- lose sodium, crospovidone, sodium starch glycolate, crosslinked polyvinylpyrrolidone (PVP), 10 and microcrystalline cellulose. In one embodiment, the pharmaceutical composition comprises a glidant, e.g., magnesium stearate, talc, colloidal silicon dioxide, sodium stearyl fumarate, and stearic acid. In one embodiment, the pharmaceutical composition comprises a coating, e.g., hydroxypropyl methylcellulose (HPMC), ethyl cellulose, shellac, polyvinyl alcohol (PVA), and gelatin. 15 In one embodiment, the pharmaceutical composition comprises a preservative, e.g., ben- zalkonium chloride, methylparaben, propylparaben, sorbic acid, and benzyl alcohol. In one embodiment, the pharmaceutical composition comprises a colorant, e.g., iron oxides, i.e. Fe2O3, FeO and Fe3O4, titanium dioxide, indigo carmine, sunset yellow, and allura red. In one embodiment, the pharmaceutical composition comprises a flavoring, e.g., aspartame, su- 20 crose, sorbitol, sodium saccharin, and peppermint oil. In one embodiment, the pharmaceutical composition comprises a solubilizer, e.g., polysorbate 80, propylene glycol, ethanol, cyclodextrins, and polyethylene glycol (PEG). In one embodiment, the pharmaceutical composition comprises a buffer system, e.g., citric acid and sodium citrate, hydrogen phosphate and dihydrogen phosphate, and acetic acid and so- 25 dium acetate. Definitions Pain Management: The compounds of the present disclosure have analgesic properties and can be effective in managing various types of pain, including neuropathic pain, cancer-related pain, and chronic pain conditions. June 25, 2025 32 / 74 TR0011P-WO2 Nausea and Vomiting: The compounds of the present disclosure have antiemetic effects, mak- ing it useful in managing nausea and vomiting associated with chemotherapy, radiation therapy, and certain medical conditions, such as AIDS. Appetite Stimulation: The compounds of the present disclosure can stimulate appetite, making it 5 beneficial for patients suffering from appetite loss and weight loss associated with conditions, such as HIV / AIDS or cancer, as well as for individuals undergoing chemotherapy. Muscle Spasticity: The compounds of the present disclosure may help reduce muscle spasms and spasticity, making it potentially useful for conditions such as multiple sclerosis (MS) and spi- nal cord injuries. 10 Glaucoma: The compounds of the present disclosure have been investigated for its potential to lower intraocular pressure, which is beneficial for individuals with glaucoma, although its effects may be temporary and require frequent dosing. Inflammatory Bowel Disease (IBD): The compounds of the present disclosure may have anti- inflammatory effects that could be beneficial in managing symptoms of inflammatory bowel dis- 15 eases, such as Crohn's disease and ulcerative colitis. Sleep Disorders: The compounds of the present disclosure may have sedative effects and could be useful in managing certain sleep disorders like insomnia, although long-term use may disrupt sleep patterns. Neurological Disorders: The compounds of the present disclosure may have neuroprotective20 properties and could be beneficial in the treatment of neurological conditions, such as Parkin- son's disease, Alzheimer's disease, and epilepsy. Anxiety and post-traumatic stress disorder (PTSD): The compounds of the present disclosure may have anxiolytic effects and could potentially be helpful in managing anxiety disorders and PTSD. 25 Medical use In one aspect, this disclosure provides a compound according to this disclosure for use in medi- cine. In one aspect, this disclosure provides a pharmaceutical composition comprising a compound according to this disclosure for use in medicine. 30 In one embodiment, this disclosure relates to a compound according to this disclosure for use in June 25, 2025 33 / 74 TR0011P-WO2 the treatment of a condition selected from the group consisting of psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxiety disorder and / or depression, neurological disor- ders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, Inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nau- 5 sea and / or vomiting, and combinations thereof. In one embodiment, this disclosure relates to a pharmaceutical composition comprising a com- pound according to this disclosure for use in the treatment of a condition selected from the group consisting of psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxi- ety disorder and / or depression, neurological disorders, sleep disorders, pain, anorexia and / or10 appetite loss, inflammation, Inflammatory Bowel Disease (IBD), muscle tension, muscle spastic- ity, spasms and / or cramps, glaucoma, and nausea and / or vomiting, and combinations thereof. In one embodiment, this disclosure relates to a compound according to this disclosure for use in the treatment of nausea and vomiting associated with chemotherapy and for appetite stimula- tion in AIDS patients experiencing weight loss. 15 In one embodiment, this disclosure relates to a compound according to this disclosure for use in the treatment of nausea and vomiting associated with chemotherapy in a patient group which has not responded to conventional antiemetic therapies. In one embodiment, this disclosure relates to a compound according to this disclosure for use in the treatment of spasticity due to multiple sclerosis (MS), wherein the compound is formulated 20 as an oromucosal spray. In one embodiment, this disclosure relates to a compound according to this disclosure for use in the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. Lennox-Gastaut syndrome and Dravet syndrome are two rare forms of epilepsy. In one embodiment, this disclosure relates to a compound according to this disclosure for use in 25 the treatment of spasticity and neuropathic pain, optionally including pain management, wherein the compound is formulated as buccal spray. In one embodiment, this disclosure relates to a compound according to this disclosure for use in therapy related to pain management, wherein the compound is formulated into and / or provided in the form of transdermal patches. Transdermal patches may be designed in such a way to 30 provide for controlled release of the compound for the purpose of pain management and other therapeutic purposes. June 25, 2025 34 / 74 TR0011P-WO2 In one embodiment, this disclosure relates to a compound according to Formula I for use in medicine I 5wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, 10 c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and 15 h) wherein R1and R2together form a ring structure selected from the group consisting of , i) R1is (C=O)OCH3and R2is allyl, June 25, 2025 35 / 74 TR0011P-WO2 wherein R3is selected from propyl, pentyl, heptyl, In one embodiment, this disclosure relates to a compound according to Formula I for use in medicine 5 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to b): 10 a) R1is allyl and R2is H, b) R1is H and R2is allyl, wherein R3is selected from propyl, pentyl, heptyl, In one embodiment, this disclosure relates to a compound according to Formula I for use in medicine June 25, 2025 36 / 74 TR0011P-WO2 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to 5 i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, 10 e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of , 15 i) R1is (C=O)OCH3and R2is allyl, wherein R3is pentyl. In one embodiment, this disclosure provides a compound for use in medicine, wherein the June 25, 2025 37 / 74 TR0011P-WO2 compound is either i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN); ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); iii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- 5 benzo[c]chromene (O-Allyl-^8-THC); iv) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1- ol (C-Allyl-^8-THC); v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen (O-Allyl-^9-THC); 10 vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C-Allyl-^9-THC); vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromene (O-Allyl-HHC); or viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 15 benzo[c]chromen-1-ol (C-Allyl-HHC). In one embodiment, this disclosure provides a compound according to any one of formula II to formula V for use in medicine: II June 25, 2025 38 / 74 TR0011P-WO2 5 In one embodiment, this disclosure provides a compound for use in medicine, wherein the com- pound is selected from the group consisting of the ∆8-THC- or ∆9-THC-derivatives of formula VI to XVI: 10 June 25, 2025 39 / 74 TR0011P-WO2 wherein R is selected from -H, -CH3, -CH2-CH3, or -CH=CH-CH3. 5 10 VIII, IX, June 25, 2025 40 / 74 TR0011P-WO2 XIII, 5 XVI. In one embodiment, this disclosure relates to a compound according to Formula I for use in the treatment of a condition selected from the group consisting of psychiatric disorders, such as10 post-traumatic stress disorder (PTSD), anxiety disorder and / or depression, neurological disor- ders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nau- sea and / or vomiting, and combinations thereof, June 25, 2025 42 / 74 TR0011P-WO2 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to 5 i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, 10 e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of , 15 i) R1is (C=O)OCH3and R2is allyl, June 25, 2025 43 / 74 TR0011P-WO2 wherein R3is selected from propyl, pentyl, heptyl, In one embodiment, this disclosure relates to a compound according to Formula I for use in the treatment of a condition selected from the group consisting of psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxiety disorder and / or depression, neurological disor- 5 ders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nau- sea and / or vomiting, and combinations thereof, I10 wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to b): a) R1is allyl and R2is H, b) R1is H and R2is allyl, 15 wherein R3is selected from propyl, pentyl, heptyl, In one embodiment, this disclosure relates to a compound according to Formula I for use in the treatment of a condition selected from the group consisting of psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxiety disorder and / or depression, neurological June 25, 2025 44 / 74 TR0011P-WO2 disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nausea and / or vomiting, and combinations thereof, 5 I wherein ring A is selected from wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, 10 b) R1is H and R2is allyl, c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, 15 g) R1is H and R2is 2-oxopropyl, and h) wherein R1and R2together form a ring structure selected from the group consisting of , June 25, 2025 45 / 74 TR0011P-WO2 i) R1is (C=O)OCH3and R2is allyl, wherein R3is pentyl. In one embodiment, this disclosure relates to a compound for use in the treatment of a condition selected from the group consisting of psychiatric disorders, such as post-traumatic stress disor- 5 der (PTSD), anxiety disorder and / or depression, neurological disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nausea and / or vomiting, and combi- nations thereof, wherein the compound provided is either i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN); 10 ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol (C-Allyl-CBN); iii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- benzo[c]chromene (O-Allyl-^8-THC); iv) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1- ol (C-Allyl-^8-THC); 15 v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen (O-Allyl-^9-THC); vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C-Allyl-^9-THC); vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 20 benzo[c]chromene (O-Allyl-HHC); or viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromen-1-ol (C-Allyl-HHC). In one embodiment, this disclosure relates to a compound according to any one of formula II to formula V for use in the treatment of a condition selected from the group consisting of psychiat-25 ric disorders, such as post-traumatic stress disorder (PTSD), anxiety disorder and / or depres- sion, neurological disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nausea and / or vomiting, and combinations thereof: June 25, 2025 46 / 74 TR0011P-WO2 5 V. In one embodiment, this disclosure relates to a compound selected from the group consisting of 10 the ∆8-THC- or ∆9-THC-derivatives of formula VI to XVI for use in the treatment of a condition June 25, 2025 47 / 74 TR0011P-WO2 selected from the group consisting of psychiatric disorders, such as post-traumatic stress disor- der (PTSD), anxiety disorder and / or depression, neurological disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, inflammatory Bowel Disease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nausea and / or vomiting, and combi- 5 nations thereof: wherein R is selected from -H, -CH3, -CH2-CH3, or -CH=CH-CH3. 10 15 IX, June 25, 2025 48 / 74 TR0011P-WO2 XIII, 5 XVI. In one embodiment, this disclosure relates to a compound according to Formula XX for use in medicine June 25, 2025 50 / 74 TR0011P-WO2 XX, wherein R1= methyl, ethyl, or propyl; wherein R2= methyl, ethyl, or propyl; 5 wherein R3= propyl, pentyl, or heptyl. In one embodiment, this disclosure relates to a compound according to Formula XXI for use in medicine XXI. 10 Kit In one aspect, this disclosure relates to a kit comprising the compound according to this disclo- sure, or the pharmaceutical composition according to this disclosure, further comprising at least one object selected from the group consisting of an applicator, a package leaflet, a transdermal patch, a second active agent, and a treatment schedule, as well as combinations thereof. June 25, 2025 51 / 74 TR0011P-WO2 Abbreviations Abbreviation Trivial name; IUPAC name CBD Cannabidiol 5 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3- diol CBDA Cannabidiolic acid 2,4-dihydroxy-3-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-6-pen- tylbenzoic acid 10 CBN Cannabinol; 6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene-1-ol ^8-THC ^8-Tetrahydrocannabinol; (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- benzo[c]chromene-1-ol 15 ^9-THC ^9-Tetrahydrocannabinol; (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen- 1-ol HHC Hexahydrocannabinol; (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 20 benzo[c]chromene-1-ol Examples Synthesis and compound characterization All reactions were performed under an atmosphere of nitrogen using solvents dried by standard procedures. Reaction progress was monitored by TLC on Polygram SIL G / UV254 silica gel 25 plates from Macherey & Nagel and on Silicagel plates 60 RP-18 F254 from Supelco. Detection June 25, 2025 52 / 74 TR0011P-WO2 of spots was effected by charring with sulfuric acid (5% in ethanol), staining by spraying the plates with an alkaline aqueous solution of potassium permanganate, staining plates in a iodine chamber or by inspection of the TLC plates under UV light (254 nm). Preparative chromatography was performed on silica gel (0.032–0.063 mm) from Macherey & 5 Nagel. NMR spectra were recorded with the following spectrometers: Bruker Avance III HD 400 (1H: 400.2 MHz; 13C: 100.6 MHz), Bruker Avance III HDX 600 (1H: 600.2 MHz; 13C: 150.9 MHz) and Bruker Avance III HDX 700 (1H: 700.3 MHz; 13C: 176.1 MHz); and calibrated for the sol- vent signal (1H: CDCl3: δ = 7.26 ppm; acetone-d6: δ = 2.05 ppm; dichlormethane-d2: δ = 5.3210 ppm; DMSO-d6: δ = 2.50 ppm;13C: CDCl3: δ =77.16 ppm; acetone-d6: δ = 29.92 ppm; dichlor- methane-d2: δ = 54.0 ppm; DMSO-d6: δ = 39.51 ppm). ESI-TOF-HRM spectrometry was performed on a Bruker MAXIS 4G spectrometer. Elemental analyses were obtained from a HEKAtech Euro EA 3000 apparatus. Optical rotations were determined with a Perkin-Elmer Polarimeter 341 in a 10 cm cuvette at 20 15 °C with a wavelength of 589 nm (Na-lamp). Melting points were measured with a Büchi Melting Point M-560 apparatus. Example 1. Preparation of CBN-derivatives 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene (O-Allyl-CBN) 20 Cannabinol (CBN) (0.7 g, 2.2 mmol) and allyl bromide (0.93 g, 3.8 mmol) were dissolved in DMF (10 ml). At room temperature K2CO3(1.13 g, 8.2 mmol) was added in one portion under vigorous stirring and stirring at room temperature was continued until TLC (petrol ether / ethyl ac- etate 10 / 1) showed complete conversion of THC to a faster moving product (16 h). Water (0.5 ml, 27 mmol) was added and the resulting mixture was stirred at room temperature for 1 h. The 25 mixture was poured into water (80 ml) and extracted with dichloromethane. The combined June 25, 2025 53 / 74 TR0011P-WO2 organic layers were successively washed with saturated NaHCO3solution and brine and dried over Na2SO4. Filtration and concentration of the solution afforded O-allyl-CBN (0.71 g, 92%) as a slightly yellow oil. HRMS m / z for [M+CH3]+calculated: 351.23186; found: 351.23197. 51H-NMR (CDCl3) significant peaks ^=8.24 (br.s, 1H, H-10), 7.17-6.96 (m, 2H, H-7,8), 6.40 (br.s, 1H, H-2), 6.36 (br.s, 1H, H-4), 6.11-6.04 (m, 1H, HC=), 5.46-5.42 (m, 1H, =CH2a), 5.26-5.23 (m, 1H, =CH2b), 4.56 (dd, 2H, OCH2), 2.47 (t, 2H, H-1’), 2.28 (s, 3H, CH3), 1.51 (s, 6H, 2 x CH3), 1.26-1.21 (m, 6H, H-2’,3’4’), 0.81 (t, 3H, H-5’). 13C-NMR (CDCl3) significant peaks ^=156.3 (C-1), 154,5 (C-4a), 144.4 (C-10a), 136.9 (C-3), 10 136.5 (C-9), 133.4 (HC=), 127.7 (C-8), 127.5 (C-10b), 127.4 (C-7), 122.3 (C-10), 117.3 (=CH2), 111.2 (C-4), 110.3 (C-6a), 105.6 C-2), 77.4 (C-6), 69.6 (OCH2), 36.1 (C-1’), 31.6, 30.7 (C-2’,3’), 27.1 (2 x CH3), 22.6 (C-4’), 21.5 (CH3), 14.1 (C-5’). 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-b 15 O-allyl-CBN (0.35 g, 1.0 mmol) was heated under N2to 185°C for 9 h to afford C-allyl-CBN (0.34 g, 97%) as a yellowish oil. HRMS m / z for [M-H]- calculated: 349.21730; found: 349.21810 1H-NMR (CDCl3): ^=8.03 (s, 1H, OH), 7.17-6.93 (m, 3H, H-7,8,10), 6.41-6.27 (m, 1H, =CH2a), 6.24 (s, 1H, H-4), 6.12-6.08 (m, 1H, HC=), 5.02-4.94 (m, 1H, =CH2b), 3.14 (q, 1H, =C-CH2a), 20 2.63 (q, 1H, =C-CH2b), 2.39 (t, 2H, H-1’), 2.30 (s, 3H, CH3), 1.56-1.47 (m, 2H, H-2’), 1.52, 1.51 (2 s, 6H, 2xCH3), 1.31-1.20 (m, 4H, H-3’,4’), 0.82 (t, 3H, H-5’). 13C-NMR (CDCl3): ^=156.4 (C-1), 153.2 (C-4a), 139.3 (C-10a), 136.8 (C-3), 130.1 (C-6a), 127.5 (4C, C-2,8,9, HC=), 126.1 (C-10), 122.4 (C-7), 118.9 (C-10b), 109.3 (H2C=), 105.2 (C-4), 80.5 (C-6), 25.3 (C-4’), 33.5 (C-3’), 31.7 (C-2’), 29.3 (CH2allyl), 27.5 (2C, CH3), 22.6 (C-1’), 22.3 (CH3), 25 14.1 (C-5’). June 25, 2025 54 / 74 TR0011P-WO2 Example 2. Preparation of ^8-THC-derivatives Method A: (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- benzo[c]chromene (O-Allyl-^8-THC) 5 ^8-Tetrahydrocannabinol (18.3 g, 58.2 mmol) and allyl bromide (16.94 g, 70 mmol) were dis- solved in DMF (100 ml). At room temperature K2CO3 (20.7 g, 150 mmol) was added in two por- tions under vigorous stirring and stirring at room temperature was continued until TLC (petrol ether / ethyl acetate 10 / 1) showed complete conversion of THC to a faster moving product (16 h). The suspension was filtered through a glass filter and the filtrate was concentrated under vac- 10 uum at the rotary evaporator (bath temperature 60°C). The concentrated solution was poured into water (200 ml) and extracted with ethyl acetate. The combined organic layers were succes- sively washed with saturated NaHCO3 solution and brine and dried over Na2SO4. Filtration and concentration of the solution afforded O-allyl-^8-THC (18.2 g, 88%) as a colorless oil. [^]D20= -560.7 (c 1.1, CHCl3). 15 HRMS m / z for [M+H]+calculated: 355.26371; found: 355.26321. 1H-NMR (CDCl3) ^=6.24 (d, 1H, H-4), 6.17 (d, 1H, H-2), 6.04-5.96 (m, 1H HC=), 5.36-5.31 (m, 2H, H-8, =CH2a), 5,21-5.18 (m, 1H, =CH2b), 4.45 (dd, 2H, OCH2), 3.17 (dd, 1H, H-10a), 2.66- 2.60 (m, 1H, H-6a), 2.42 (t, 2H, H-1’), 2.08-2.04 (m, 1H, H-7a), 1.75-1.68 (m, 3H, H-7b, H-2’), 1.61 (s, 3H, CH3-9), 1.30 (s, 3H, CH3-6), 1.30-1.20 (m, 4H, H-3’,4’), 1.02 (s, 3H, CH3-6), 0.82 (t, 20 3H, H-5’). 13C-NMR (CDCl3) ^=157.9 (C-1), 154.4 (C-4a), 142.5 (C-3), 135.1 (C-9), 133.7 (=CH), 119.2 (C- 8), 118.9 (=CH2), 112.2 (C-10b), 110.4 (C-2), 104.3 (C-4), 68.9 (OCH2), 45.2 (C-6a), 36.4 (C- 1’), 36.0 (C-10), 31.8 (C-3’), 31.7 (C-4’), 30.8 (C-2’), 28.4 (C-10a), 27.8 (C-4’), 23.6 (CH3), 22.5 (CH3), 19.4 (CH3), 14.1 (C-5’). 25 Method B: ( )-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- June 25, 2025 55 / 74 TR0011P-WO2 ^8-Tetrahydrocannabinol (2.01 g, 6.4 mmol) and potassium t-butanoate (0.9 g, 8.0 mmol) in DMF (8 ml) were stirred under nitrogen at room temperature for 15 minutes. Allyl bromide (1.1 5 g, 9.0 mmol) was dropped in with cooling so that the temperature did not exceed 40°C. The mix- ture was stirred at room temperature until TLC (petrol ether / ethyl acetate 10 / 1) showed com- plete conversion of THC to a faster moving product (2 h). The mixture was poured into water (100 ml) and extracted with dichloromethane. The combined organic phases were washed with saturated aqueous NaHCO3 solution and brine and dried over Na2SO4. Filtration, concentration10 and storage under vacuum (10-2torr) overnight afforded O-allyl-^8-THC (2.2 g, 99%) as a color- less oil. n-1-ol (C- 15 O-allyl-^8-THC (1.0 g, 2.8 mmol) was heated under N2to 185-190°C for 4 h to afford C-allyl-^8- THC in quantitative yield as a colorless oil. [^]D20= -303.3 (c 1.0, CHCl3) HRMS m / z for [M-H]- calculated: 353.24806; found: 353.24860. 1H-NMR (CDCl3) ^=6.23 (s, 1H, H-4), 5.96-5.86 (m, 1H, -CH=), 5,35 (d, 1H, H-8), 5.11-5.04 (m,20 2H, =CH2), 3.29-3.28 (m, 2H, CH2-C=), 3,15-1.10 (m, 1H H-10a), 2.68-2.60 (m, 2H, H-1’), 2.44- 2.38 (m, 2H, H-9a,6a), 2.08-2.04 (m, 1H, H-7a), 1.78-1.70 (m, 3H, H-7b,9b,10b), 1.62 (s, 3H, June 25, 2025 56 / 74 TR0011P-WO2 CH3), 1.43-1.41 (m, 1H, H-2’), 1.30 (s, 3H, CH3), 1.24-1.21 (m, 4H, H-4’,3’), 1.02 (s, 3H, CH3), 0.81 (t, 3H, H-5’). 13C-NMR (CDCl3) ^=154.3 (C-1), 153.0 (C-4a), 140.6 (C-3), 136.8 (-HC=), 134.9 (C-2), 119.4 (C-8), 116.4 (=CH2), 114.0 (C-9), 111.6 (C-10b), 110.8 (C-4), 76.5 (C-6), 45.2 (C-6a), 36.2 (C- 5 10), 33.7 (C-1’), 31.9 (C-2’), 30.7 (CH2-allyl), 28.1 (C-3’), 27.6 (CH3), 23.6 (CH3), 22.6 (C-4’), 18.5 (CH3), 14.1 (C-5’). Example 3. Preparation of ^9-THC-derivatives (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromene (O-Allyl-^9-THC) 10 ^9-Tetrahydrocannabinol (1.0 g, 3.2 mmol) and allyl bromide (1.4 g, 5.7 mmol) were dissolved in DMF (20 ml). At room temperature K2CO3(1.57 g, 11.4 mmol) was added in one portion under vigorous stirring and stirring at room temperature was continued until TLC (petrol ether / ethyl ac- etate 10 / 1) showed complete conversion of THC to a faster moving product (14 h). The suspen-15 sion was filtered through a glass filter and the filtrate was concentrated under vacuum at the ro- tary evaporator (bath temperature 60°C). The concentrated solution was poured into water (80 ml) and extracted with ethyl acetate. The combined organic layers were successively washed with saturated NaHCO3solution and brine and dried over Na2SO4. Filtration and concentration of the solution afforded O-allyl-^9-THC (1.1 g, 97%) as a colorless oil. 20 [^]D20= -150.0 (c 1.2, CHCl3). HRMS m / z for [M+H]+calculated: 355.26371; found: 355.26246. 1H-NMR (CDCl3) ^=6.26 (d, 1H, H-4), 6.17 (d, 1H, H-2), 6.06-5.99 (m, 1H HC=), 5.41-5.36 (m, 1H, H-9), 5.21-5.18 (m, 1H, =CH2), 4.49 (d, 2H, OCH2), 3.14 (dd, 1H, H-10a), 2.42 (t, 2H, H-1’), 2.08-2.06 (m, 3H, H-6a,8), 1.84-1.81 (m, 1H, H-7a), 1.58 s, CH3), 1.61-1.58 (m, 2H, H-2’), 1.35 25 (s, 3H, CH3), 1.30-1.19 (m, 4H, H-3’,4’), 1.01 (s, 3H, CH3), 0.81 (t, 3H, H-5’). June 25, 2025 57 / 74 TR0011P-WO2 13C-NMR (CDCl3) ^=157.4 (C-1), 154.5 (C-4a), 142.4 (C-3), 133.6 (=CH), 133.2 (C-9), 125.1 (C- 10), 117.0 (=CH2), 110.7 (C-10b), 110.4 (C-2), 104.2 (C-4), 77.1 (C-6a), 68.9 (OCH2), 45.9 (C- 6a), 36.4 (C-1’), 36.0 (C-8), 31.8, 31.7, 30.8 (C-2’,3,4’), 27.8 (CH3), 23.6 (CH3), 19.4 (CH3), 14.1 (C-5’). 5 (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol (C- Allyl-^9-THC). O-allyl-^9-THC (1.0 g, 3.4 mmol) was heated under N2to 160-170°C for 5 h to afford C-allyl-^9- THC (0.95 g, 95%) as a yellowish oil. 10 [^]D20= -170.0 (c 0.5, CHCl3) HRMS m / z for [M-H]- calculated: 353.24806; found: 353.24872. 1H-NMR (CDCl3) ^=6.22 (s, 1H, H-4), 5.93-5.86 (m, 2H, H-10, CH=), 5.11-5.04 (m, 2H, =CH2), 3.32-3.28 (m, 3H, H-10a, CH2-C=), 2.48-2.35 (m, 3H, H-6a,H-1’), 2.08 (br s, 2H, H-8), 1.86-1.80 (m, 1H, H-7), 1.60 (s, 3H, CH3), 1.47-1.32 (m, 7H, CH3, H-2’,3’), 1.00 (s, 3H, CH3), 0.80 (t, 3H, 15 H-5’). 13C-NMR (CDCl3) ^=153.5 (C-1), 152.9 (C-4a), 140.7 (C-3), 139.9 (-HC=), 134.3 (C-9), 124.1 (C-10), 118.2 (=CH2), 114.1 (C-2), 110.7 (C-4), 110.0 (C-10b), 76.8 (C-6), 48.1 (C-6a), 33.9 (C- 10a), 33.7 (C-1’), 31.9 (CH2allyl), 31.3, 30.9 (C-2’,3’), 23.4 (CH3), 19.2 (CH3), 14.1 (C-5’). Example 4. Preparation of HHC-derivatives 20 June 25, 2025 58 / 74 TR0011P-WO2 benzo[c]chromene (O-Allyl-HHC) Hexahydrocannabinol (5:1 mixture of 9R / 9S isomers) (1.1 g, 3.5 mmol) and allyl bromide (0.96 g, 7.9 mmol) were dissolved in DMF (15 ml). At room temperature K2CO3 (1.57 g, 11.4 mmol) 5 was added in one portion under vigorous stirring and stirring at room temperature was contin- ued until TLC (petrol ether / ethyl acetate 10 / 1) showed complete conversion of THC to a faster moving product (16 h). The suspension was filtered through a glass filter and the filtrate was concentrated under vacuum at the rotary evaporator (bath temperature 60°C). The concentrated solution was poured into water (80 ml) and extracted with ethyl acetate. The combined organic 10 layers were successively washed with saturated NaHCO3 solution and brine and dried over Na2SO4. Filtration and concentration of the solution afforded O-allyl-HHC (5:1 mixture of 9R / 9S isomers) (1.17 g, 97%) as a colorless oil. HRMS m / z for [M+H]+calculated: 355.26371; found: 355.26246. 1H-NMR (CDCl3) significant peaks ^=6.21 (d, 1H, H-2), 6.15 (d, 1H, H-4), 6.13-5.96 (m, 1H 15 HC=), 5.39-5.15 (m, 2H, =CH2), 4.44 (q, 2H, (R)-OCH2), 4.40 (q, 2H, (S)-OCH2), 2.41-2.34 (m, 1H, H-10a), 2.02-2.01 (m, 2H, (S)-H-10), 1.78-1.74 (m, 2H, (R)-H-10), 1.58-1.49 (m, 1H, (R)-H- 9), 1.39-1.35 (m, 1H, (S)-H-9), 1.26 (d, 3H, (R)-CH3), 1.24 (d, 3H, (S)-CH3), 0.85-0.76 (m, 3H, H-5’), 0.46 (q, 3H, (S)-CH3). 13C-NMR (CDCl3) significant peaks ^=157.9 ((R)-C-1), 157.8 ((S)-C-1), 142.3 ((R)-C-3), 142.2 20 ((S)-C-3), 133.7 (=CH), 116.8 ((S)-H2C=), 116.6 ((R)-H2C=), 110.3 (C-4), 104.3 (C-4a), 68.9 ((S)-OCH2), 68.8 ((R)-OCH2), 50.3 ((S)-C-6a), 49.4 ((R)-C-6a), 22.9 ((S)-CH3), 22.6 ((R)-CH3), 14.1 (C-5’). June 25, 2025 59 / 74 TR0011P-WO2 O-allyl-HHC (0.9 g, 2.5 mmol) was heated under N2 to 185°C for 6 h to afford C-allyl-HHC (0.85 g, 94%) as a yellowish oil. 5 HRMS m / z for [M-H]- calculated: 355.26425; found: 355.26441 1H-NMR (CDCl3) significant peaks ^=7.18 (s, 1H, OH), 5.92-5.81 (m, 1H, HC=), 5.10-5.0 (m, 2H, (R)-H2C=), 4.96-4.81 (m, 2H, (S)-H2C=), 3.30-3.25 (2H, CH2-C=), 2.44-2.34 (m, 1H, H-10a), 1.28 (s, 3H, (R)-CH3), 1.25 (s, 3H, (S)-CH3), 0.85-0.77 (m, 6H, CH3, H-5’). 13C-NMR (CDCl3) significant peaks ^=137.3 ((S)-HC=), 136.9 ((R)-HC=), 116.3 ((S)-=CH2), 10 116.2 ((R)-=CH2), 110.6 (C-4), 50.2 ((R)-C-10), 49.4 ((S)-C-10), 30.6 (H2Callyl), 28.0, 27.6 (CH3), 23.2 ((S)-CH3), 22.6 (R)-CH3), 14.1 (C-5’) Example 5. Preparation of a ^8-THC carbonate derivative (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-yl methyl carbonate 15 C-Allyl-^8-THC (35.5 g) was dissolved in 200 ml dichloromethane and was contacted sequen- tially with 21.0 ml triethylamine (TEA) and 0.5 g 4-dimethylaminopyridine (DMAP) under vigor- ous stirring and in an inert atmosphere. After stirring for 15 minutes, 9.27 ml methyl chlorofor- mate (MCF) were added dropwise at a rate which provides for gentle boiling of the dichloro- 20 methane solvent under reflux conditions. The reaction was monitored by TLC using a June 25, 2025 60 / 74 TR0011P-WO2 MeOH:AcOH 19:1 (v / v) mixture. Upon apparent completion of the reaction, the mixture was quenched with 10 ml methanol and then washed with ice cold 3% aqueous HCl solution. The organic phase was separated and sequentially washed with aqueous saturated NaHCO3 solu- tion and dilute brine solution which affords the 2-allyl-1-methyl carbonate ^8-THC derivative. 5 The organic solution was passed through silica gel (0.032–0.063 mm) from Macherey & Nagel under removal of a forerun and the product run was concentrated by evaporation followed by subsequent degassing. The target compound was obtained in greater than 99% purity. 1H NMR (CDCl3): δ=6.54 (s, 1H, H-4), 5.78-5.71 (m, 1H, HC=), 5.34 (s, 1H, H-8), 4.89-4.84 (m, 2H =CH2), 3.76 (s, 3H, OCH3), 3.30-3.11 (ddd, 2H, CH2-C=), 2.71-2.70 (m, 1H, H-10a), 2.63- 10 2.37 (m, 4H, H-6a, 10, 1’), 2.07-2.03 (m, 1H, H-10), 1.84-1.68 (m, 2H, H-7), 1.50-1.44 (m, H-2’), 1.29 (s, 6H, CH3), 1.29-1.26 (m, 4H, H-3’, 4’), 1.02 (s, 3H, CH3), 0.81 (t, 3H, H-5’). 13C NMR (CDCl3): δ=153.4 (O-C=O), 152.7 (C-4a), 148.9 (C-1), 141.5 (C-3), 136.5 (HC=), 134.3 (C-9), 121.7 (C-2), 119.5 (C-4), 117.0 (C-10b), 116.1 (C-8), 114.9 (H2C=), 77.4 (C-6), 55.5 (OCH3), 44.9 (C-6a), 36.1 (C-10), 32.7 (C-1’), 31.9 (C-10a), 31.0 (CH2allyl), 30.6 (C-3’), 30.4 (C- 15 2’), 23.5 (CH3), 22.6 (C-4’), 18.5 (CH3), 14.1 (C-5’). HRMS m / z for [MH]+calculated: 413.26918, found: 413.26895 Example 6. Preparation of O-Allyl-O-acetyl-CBDA-methyl-ester 20 2O-Acetyl-CBDA-methylester (7.1 g, 17 mmol) and allyl bromide (2.66 g, 22 mmol) were dis- solved in DMF (40 ml). At room temperature K2CO3(3.45 g, 25 mmol) was added in one portion under vigorous stirring and stirring at room temperature was continued until TLC (petrol June 25, 2025 61 / 74 TR0011P-WO2 ether / ethyl acetate 10 / 1) showed complete conversion of the starting material into a faster mov- ing product (16 h). The suspension was filtered through a glass filter and the filtrate was con- centrated under vacuum at the rotary evaporator (bath temperature 60 °C). The concentrated solution was poured into water (100 ml) and extracted with ethyl acetate. The combined organic 5 layers were successively washed with saturated NaHCO3solution and brine and dried over Na2SO4. Filtration and concentration of the solution afforded O-allyl-O-acetyl-CBDA-methyl es- ter (7.76 g, quant.) as a slightly yellow oil. HRMS m / z for [MH]+calculated: 455.27975, found: 455.28091 1H NMR (CDCl3): δ=6.37 (s, 1H, H-5), 6.00-5.86 (m, 1H, HC=), 5.36-5.29 (m, 2H, =CH2), 5.19-10 5.10 (m, 3H, H-6’, =CH2), 4.40-4.37 (m, 2H, OCH2), 3.76 (s, 3H, COOCH3), 2.95-2.89 (m, 1H, H- 3’), 2.47-2.39 (m, 1H, H-2’), 2.09-2.07 (m, 1H, H-4’), 1.93-1.89 (m, 1H, H-4’), 1.69-1,66 (m, 1H, H-3’), 1.58 (s, 3H, CH3), 1.51-1.43 (m, 2H, H-2’’), 1.50 (s, 6H, CH3), 1.20-1.15 (m, 4H, H-3’’, 4’’), 0.81 (t, 3H, H-5’’). 13C NMR (CDCl3): δ=170.4 (C=O), 169.3 (C=O), 149.9, 140.1, 132.3, 125.3, 124.7, 116.6, 109.1 15 (Cq), 133.3 (HC=), 125.4 (C-6’), 116.7 (C-5), 69.1 (OCH2), 52.0 (OCH3), 44.6 (C-2’), 33.8, 31.8, 30.9, 30.8, 29.5, 22.5 (CH2), 23.5, 22.5, 19.7 (CH3), 14.0 (C-5’’). The synthesis of the starting material 2O-Acetyl-CBDA-methylester has been described in the art, e.g., WO 2023 / 099549 A1, which synthesis is hereby incorporated by reference. Example 7. In-silico binding affinities of the synthesised C-allyl derivatives towards the 20 CB1 and CB2 receptor Table 1 shows the AutoDock (Morris et al., J. Computational Chemistry 16: 2785, 2009) and Le- Dock (Wang et al., Phys. Chem. Chem. Phys.18: 12964, 2016) in-silico calculated free energy scorings, i.e., the binding affinities for the C-allyl derivatives C-allyl-Δ9-THC, C-allyl- Δ8-THC, C- allyl-HHC, and C-allyl-CBN, towards the two cannabinoid receptors, CB1 and CB2, in compari-25 son to the in-silico calculated binding affinities of ^9-THC being -11.04 kcal / mol for CB1 and - 5.4 kcal / mol for CB2 (Haghdoost et al. Pharmaceuticals 17: 637, 2024). In general, the synthesised C-allyl derivatives C-allyl-Δ9-THC-, C-allyl- Δ8-THC-, C-allyl-HHC and C-allyl-CBN, show lower in-silico calculated binding affinities to CB1 and CB2 receptors in comparison to the in-silico calculated binding affinities of ^9-THC. The energetic differences of 30 the in-silico calculated binding affinities of the synthesised C-allyl derivatives between the two cannabinoid receptors, CB1 and CB2, are less pronounced in comparison to the energetic dif- ference of the in-silico calculated binding affinities of ^9-THC. This suggests a diminished June 25, 2025 62 / 74 TR0011P-WO2 psychotropic effect of the synthesised C-allyl derivatives and a more pronounced physiological effect of the synthesised C-allyl derivatives associated with CB2 receptor binding. Table 1: In-silico binding affinities of C-allyl derivatives towards the CB1 and CB2 receptor 5 Example 8. Partition coefficient, acidity and solubilty Using ChemDraw Professional software (Version 23.1.2.7), the partition coefficient [n-Oc- tanol / Water] was calculated according to three different approaches, i.e. according to Crippen (J. Chem. Inf. Comput. Sci.27: 21, 1987), Viswanadhan (J. Chem. Inf. Comput. Sci.29: 163, 1989), and Broto (Eur. J. Med. Chem.- Chim.Theor.19: 71, 1984). Additionally, the acidity in the 10 form of the pKa value and the solubilty S (mol / l) presented as the Log10 S value were derived using ChemDraw Professional software. Said data were generated for the synthesised C-allyl derivatives C-allyl-Δ9-THC, C-allyl- Δ8-THC, C-allyl-HHC and C-allyl-CBN, as well as the synthe- sised O-allyl derivatives O-allyl-Δ9-THC, O-allyl- Δ8-THC, O-allyl-HHC and O-allyl-CBN, in com- parison to Δ9-THC, Δ8-THC, HHC and CBN. 15 Table 2: The partition coefficient [n-Octanol / Water] according to Crippen, Viswanadhan and Broto, acidity and solubility values were computed for the synthesised C-allyl derivatives C-allyl- Δ9-THC, C-allyl- Δ8-THC, C-allyl-HHC and C-allyl-CBN, as well as the synthesised O-allyl deriv- atives O-allyl-Δ9-THC, O-allyl- Δ8-THC, O-allyl-HHC and O-allyl-CBN, in comparison to Δ9-THC, Δ8-THC, HHC and CBN. / l) June 25, 2025 63 / 74 TR0011P-WO2 June 25, 2025 64 / 74

Claims

TR0011P-WO2 Claims 1. A compound according to Formula I 5wherein R1and R2are chosen in combination according to any one of the following options a) to i): a) R1is allyl and R2is H, b) R1is H and R2is allyl, 10 c) R1is H and R2is 1-propenyl, 2-butenyl, 2-pentenyl, or 2,4-hexadienyl, d) R1is H and R2is 3-hydroxy-propyl, e) R1is H and R2is butyryl aldehyde, f) R1is H and R2is propionyl acid, g) R1is H and R2is 2-oxopropyl, and 15 h) wherein R1and R2together form a ring structure selected from the group consisting of, June 25, 2025 65 / 74TR0011P-WO2 i) R1is (C=O)OCH3and R2is allyl, wherein R3is selected from propyl, pentyl, heptyl,2. The compound according to claim 1, being either i) 1-(Allyloxy)-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromene; 5 ii) 2-Allyl-6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol; iii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H- benzo[c]chromene; iv) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen- 1-ol; 10 v) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen; vi) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen- 1-ol; vii) (6aR,10aR)-1-(allyloxy)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- 15 benzo[c]chromene; or viii) (6aR,10aR)-2-allyl-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6H- benzo[c]chromen-1-ol.

3. The compound according to any of claims 1 or 2, selected from formula II to formula V:20 II June 25, 2025 66 / 74TR0011P-WO2 54. The compound according to claim 1, selected from formula VI to formula XVI:wherein R is selected from -H, -CH3, -CH2-CH3, or -CH=CH-CH3. 10 VI, June 25, 2025 67 / 74TR0011P-WO2 XIV,5 XVI.

5. The compound according to any of the claims 1 to 4, characterized by one or more of the following features: a. having a reduced psychoactive effect as compared to ∆9-Tetrahydrocannabinol (∆9- THC); 10 b. having an elevated effect selected from the group consisting of pain relief, appetite stim- ulation, anti-inflammatory properties, muscle relaxation, anxiety reduction, and antie- metic effect reduction, as well as combinations thereof, as compared to ∆9-Tetrahydro- cannabinol (∆9-THC); c. having an increased lipophilicity as compared to ∆9-Tetrahydrocannabinol (∆9-THC). 15 6. Process for the synthesis of the compounds according to claim 2, comprising the steps of: a. Providing a starting compound selected from the group of Δ9-THC, Δ8-THC, HHC, and CBN, and dissolving the starting compound in a solvent; June 25, 2025 70 / 74TR0011P-WO2 b. Reacting the starting compound with allyl-bromide to obtain an intermediate product; c. Extracting the intermediate product; d. Washing and drying the intermediate product; e. Optionally heating the intermediate product; 5 f. Optionally obtaining a second product; and g. Optionally isolating the second product.

7. Pharmaceutical composition comprising a compound according to any of the claims 1 to 4.

8. The pharmaceutical composition of claim 7, further comprising - at least one excipient selected from the group consisting of fillers such as lactose, micro- 10 crystalline cellulose, dicalcium phosphate, mannitol, starches, e.g., corn starch; - optionally a binder, e.g., starch paste, povidone (polyvinylpyrrolidone), hydroxypropyl cellulose, methylcellulose, carboxymethyl cellulose sodium; - optionally a disintegrant, e.g., croscarmellose sodium, crospovidone, sodium starch gly- colate, crosslinked polyvinylpyrrolidone (PVP), microcrystalline cellulose; 15 - optionally a glidant, e.g., magnesium stearate, talc, colloidal silicon dioxide, sodium stearyl fumarate, stearic acid; - optionally a coating, e.g., hydroxypropyl methylcellulose (HPMC), ethyl cellulose, shel- lac, polyvinyl alcohol (PVA), gelatin; - optionally a preservative, e.g., benzalkonium chloride, methylparaben, propylparaben, 20 sorbic acid, benzyl alcohol; - optionally a colorant, e.g., iron oxides, titanium dioxide, indigo carmine, sunset yellow, allura red; - optionally a flavoring, e.g., aspartame, sucrose, sorbitol, sodium saccharin, peppermint oil; 25 - optionally a solubilizer, e.g., polysorbate 80, propylene glycol, ethanol, cyclodextrins, pol- yethylene glycol (PEG); June 25, 2025 71 / 74TR0011P-WO2 - optionally a buffer system, e.g., citric acid and sodium citrate, hydrogen phosphate and dihydrogen phosphate, acetic acid and sodium acetate.

9. Compound according to any one of claims 1 to 4 for use in medicine, or the pharmaceutical composition according to any of claims 7 and 8 for use in medicine. 5 10. Compound according to any one of claims 1 to 4 for use in the treatment of a condition se- lected from the group consisting of psychiatric disorders, such as post-traumatic stress dis- order (PTSD), anxiety disorder and / or depression, neurological disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, Inflammatory Bowel Disease (IBD), mus- cle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nausea and / or vomit- 10 ing, and combinations thereof, or the pharmaceutical composition according to any of claims 6 and 7, for use in the treatment of a condition selected from the group consisting of psychiatric disorders, such as post-trau- matic stress disorder (PTSD), anxiety disorder and / or depression, neurological disorders, sleep disorders, pain, anorexia and / or appetite loss, inflammation, Inflammatory Bowel Dis-15 ease (IBD), muscle tension, muscle spasticity, spasms and / or cramps, glaucoma, and nau- sea and / or vomiting, and combinations thereof.

11. Kit comprising the compound according to any one of claims 1 to 4, or the pharmaceutical composition according to any of claims 7 and 8, further comprising at least one object se- lected from the group consisting of an applicator, a package leaflet, a transdermal patch, a 20 second active agent, and a treatment schedule, as well as combinations thereof.

12. A compound according to Formula XXXX, June 25, 2025 72 / 74TR0011P-WO2 wherein R1= methyl, ethyl, or propyl; wherein R2= methyl, ethyl, or propyl; wherein R3= propyl, pentyl, or heptyl.

13. The compound according to claim 11, selected from formula XXI5 XXI.

14. Pharmaceutical composition comprising a compound according to claim 12 or claim 13.

15. Compound according to claim 12 or claim 13 for use in medicine, or the pharmaceutical composition according to claim 14 for use in medicine. 10 June 25, 2025 73 / 74

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