Genipin hydrogenate derivatives that can bind to keratin tissue

Abstract

This application relates to a topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound that can covalently bond to the skin is a compound of formula (I), or a tautomer thereof and / or a pharmaceutically acceptable salt thereof, where R 1 L1 represents hydrogen, or a protecting group that can be hydrolyzed under physiological conditions after application of the topical composition to the skin; L1, L2, and L3 independently represent a linker group or are absent; and A1, A2, and A3 independently represent a)C1~C 30 Partial, H, hydroxyl, amino, or halogen, or b) C1-C 60 Represents a part or polymer part, and at least one of A1, A2 and A3 is C1-C of group b). 60 It is a part or polymer part, and C1-C of group b) 60 The present invention relates to a topical composition in which the polymer portion is configured to act as a skin moisturizer, insecticide, skin whitening agent, or pharmaceutical, and / or b2) after cleavage from the 3,4-dihydro-2H-pyran portion, and L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position to the carbon atoms marked "a" and "b", respectively. [Formula 1] JPEG2026519286000116.jpg29128

Description

【Technical Field】 【0001】 Cross - reference to related applications This application is titled both "Compounds attachable to keratinous tissues", both claim the benefit of European Patent Application Nos. 23178139.4 and 23178138.6, both filed on June 7, 2023, the contents of which are incorporated herein by reference. 【0002】 The present disclosure relates to compounds that can be graft - polymerized reliably and efficiently onto keratinous tissues such as the skin. More specifically, the present disclosure relates to conjugate molecules comprising an active ingredient and a specifically selected anchoring moiety that, when attached to a keratinous tissue, cannot form an extended conjugated π - system. Thus, the attached anchor moiety does not impart color and allows the compounds of the present disclosure to remain visually unobtrusive after binding to the tissue. The present disclosure also relates to topical compositions containing these compounds, as well as to various methods and applications of these compounds. 【Background Art】 【0003】 Genipin is a natural compound (1R,4aS,7aS) - 1 - hydroxy - 7 - (hydroxymethyl) - 1,4a,5,7a - tetrahydrocyclopenta[c]pyran - 4 - carboxylic acid methyl (CAS RN. 6902 - 77 - 8) and has the following structure. 【0004】 【Chemical formula】 【0005】 Genipin can bind irreversibly to keratinous tissues. For example, keratin in the skin contains lysine with aliphatic amino side - chains. These amino side - chains react with the cyclic hemi - acetal structure of genipin according to the following representative reaction scheme. 【0006】 【Chemical formula】 【0007】 The final conjugated genipin derivative is colored a deep blue. Due to its deep blue color, genipin is commercially used as a tattoo dye in semi-permanent tattoos. 【0008】 This skin-binding property makes genipin an interesting candidate for binding various active ingredients to the skin, such as moisturizers, insecticides, especially insect repellents, skin whitening agents, fragrance precursors, and pharmaceuticals. However, its dark blue color is aesthetically unappealing to many, especially when applied to the face or larger areas of skin. Therefore, although genipin has many functional groups readily available for binding active ingredients, it has not been seriously considered as a means of binding active ingredients to the skin. 【0009】 However, it is highly desirable to have a compound that allows the active ingredient to adhere to the skin in an inconspicuous manner. [Overview of the Initiative] 【0010】 In extensive research on genipin chemistry, the inventors concluded that a wide range of genipin derivatives can reliably and efficiently bind to keratinous tissues such as skin. This strong binding chemistry may be attributable to the 3,4-dihydro-2H-pyran moiety and is largely unaffected by further substitution of the 3,4-dihydro-2H-pyran moiety. This finding is further supported, for example, in literature describing that oleuropein and aucubin activated by β-glucosidase have very similar, but stronger, protein denaturation, protein crosslinking, and lysine alkylation activity than glutaraldehyde. See Konno et al., PNAS, 1999, 96(16)9159-9164. Deglycosylated oleuropein and aucubin have the following structures: 【0011】 [ka] 【0012】 Therefore, the inventors have come to recognize that a variety of 3,4-dihydro-2H-pyran derivatives can bind to the skin effectively and irreversibly. 【0013】 Furthermore, in their research, the inventors surprisingly found that the hydrogenated genipin derivatives remained substantially colorless after reaction with lysine. A representative example is shown in the following reaction scheme. 【0014】 【Chemical Formula】 【0015】 The colorless (or almost colorless and thus visually imperceptible on the skin) state of the hydrogenated genipin derivative bound to the skin can be explained by the fact that the 1,4-dihydropyridine moiety formed using lysine does not confer a conjugated π-electron system with the double bond present in the cyclopentene moiety of genipin (and not present in hydrogenated genipin). 【0016】 The inventors have come to the conclusion that a variety of 3,4-dihydro-2H-pyran derivatives bind to the skin, for example, invisibly, as long as the 3,4-dihydro-2H-pyran derivatives are selected such that the formation of a conjugated π-electron system in the 1,4-dihydropyridine moiety bound to the skin is avoided. Therefore, 3,4-dihydro-2H-pyran derivatives that meet this requirement are particularly useful as a visually imperceptible fixing moiety for efficiently, irreversibly, and invisibly binding an active ingredient to a keratinous tissue such as the skin. 【0017】 Finally, the active ingredient may be stably bound to the 3,4-dihydro-2H-pyran derivative, or it may be bound to the 3,4-dihydro-2H-pyran derivative in such a way that it is released over time, for example, by hydrolysis or enzymatic cleavage of the functional group linking the active ingredient to the 3,4-dihydro-2H-pyran derivative. Suitable functional groups that provide sustained release are well known in the art and readily available to those skilled in the art. For example, see V. Redasani, and S. Bariwidely, *Prodrug Design-Perspectives, Approaches and Applications in Medicinal Chemistry*, which is incorporated herein by reference in its entirety. st See ed., 2015, ISBN: 9780128035191. 【0018】 Accordingly, in a first aspect, the present disclosure relates to a topical composition comprising a compound that can be covalently bonded to the skin and an excipient suitable for topical administration, wherein the compound that can be covalently bonded to the skin is a compound of formula (I). 【0019】 [ka] 【0020】 In the compound of formula (I), R 1 L1 represents a protecting group that can be hydrolyzed under physiological conditions after application of a topical composition to the skin or by hydrogen. L1, L2, and L3 independently represent a linker group or are absent. A1, A2, and A3 independently represent a) Group: C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) Group: C1~C 60 It represents a part or polymer portion. 【0021】 b) C1~C 60The partial or polymeric part carries the active ingredient / active component. Therefore, at least one of A1, A2 and A3 is C1 to C of group b) 60 is a partial or polymeric part. 【0022】 C1 to C of group b) 60 The partial or polymeric part is subdivided into two subgroups b1) and b2). 【0023】 C1 to C of group b1) 60 The partial or polymeric part is configured to act as a skin moisturizer, insecticide, skin whitening agent, or pharmaceutical. 【0024】 In other words, this means that, here and for all other aspects of the present disclosure, C1 to C of group b1) 60 the partial or polymeric part is a skin moisturizing part, a part providing insecticidal activity, a skin whitening part or a pharmaceutical active part while being attached to the remaining part of the 3,4-dihydro-2H-pyran part. 【0025】 Additionally or alternatively, this means that, here and for all other aspects of the present disclosure, C1 to C of group b1) 60 the partial or polymeric part is a skin moisturizer, insecticide, skin whitening agent, or pharmaceutical. <0001​​​​​​​​​​​​​In other words, this applies here and to all other aspects of this disclosure, to C1-C of group b2). 60 This means that the portion or polymer portion provides its skin moisturizing activity, insecticidal activity, skin whitening activity, olfactory effect, or pharmaceutically active activity after cleavage or release from the rest of the 3,4-dihydro-2H-pyran portion. 【0029】 Additionally or alternatively, this applies here and to all other aspects of the present disclosure, b2) C1-C 60 This means that the portion or polymer portion is a skin moisturizer, insecticide, skin whitening agent, fragrance, or pharmaceutical after cleavage or release from the rest of the 3,4-dihydro-2H-pyran portion. 【0030】 Additionally or alternatively, this applies here and to all other aspects of the present disclosure, b2) C1-C 60 It means that the portion or polymer portion is a skin moisturizer, insecticide, skin whitening agent, fragrance, or pharmaceutical product that can be cleaved or released from the rest of the 3,4-dihydro-2H-pyran portion after the compound has covalently bonded to the skin. 【0031】 In some cases, for example in the case of fragrances, the bound active ingredient is active only after release, but the two subgroups b1) and b2) are not necessarily mutually exclusive. For example, a polyol humectant may provide its activity not only while bound to the 3,4-dihydro-2H-pyran moiety, but also when released from the 3,4-dihydro-2H-pyran moiety. 【0032】 As described above, the 3,4-dihydro-2H-pyran derivatives of this disclosure are selected such that the formation of a conjugated π-electron system with respect to the 1,4-dihydropyridine moiety bound to the skin is essentially avoided. Accordingly, the compounds of this disclosure are limited such that L1-A1 and L2-A2 do not represent moieties containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. 【0033】 The compound of the above formula may exist as a tautomer and / or as a pharmaceutically acceptable salt. 【0034】 In a second aspect, the present disclosure relates to a compound of formula (I), 【0035】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. This relates to compounds of formula (I), or their tautomers and / or pharmaceutically acceptable salts, for use in medicine. 【0036】 In a third aspect, the present disclosure relates to a compound of formula (I), 【0037】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. The present invention relates to a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, for use in the treatment of skin-related diseases, allergic conditions, pain, or inflammation. 【0038】 In a fourth aspect, the present disclosure relates to a compound of formula (I), 【0039】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety C1-C 60 It is a part or a polymer part, L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. For medical use, particularly in skin-related disorders, allergic conditions, pain, or inflammation, the pharmaceutical product relates to a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, which are released over a period of hours or days. 【0040】 In a fifth aspect, the disclosure relates to the use of the topical composition according to the first aspect as a skin moisturizer, insecticide, particularly insect repellent, skin whitening agent, or fragrance agent. 【0041】 In a sixth aspect, the disclosure relates to a method of using a topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound that can covalently bond to the skin is a compound of formula (I), 【0042】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Consistently configured to act as a skin moisturizer, insecticide, or skin whitening agent, and / or b2) After cleavage from the 3,4-dihydro-2H-pyran moiety, it is configured to act as a skin moisturizer, insecticide, skin whitening agent, or fragrance. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. The method relates to a method that includes applying a topical composition to the skin. 【0043】 In a seventh aspect, the Disclosure relates to a method for treating a domesticated animal or livestock, the method comprising applying a topical composition to the skin and / or coat of the domesticated animal or livestock, the topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, the compound that can covalently bond to the skin being a compound of formula (I), 【0044】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as an insecticide and / or b2) It is configured to act as an insecticide after cleavage from the 3,4-dihydro-2H-pyran moiety. The method relates to a method in which L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. 【0045】 In the eighth aspect, the disclosure is specifically independent of the compounds of the disclosure themselves, i.e., the topical compositions. [Brief explanation of the drawing] 【0046】 [Figure 1] This is a reaction scheme for the synthesis of the compounds of this disclosure, which contain erythritol as an active ingredient. [Figure 2] This is a reaction scheme for the synthesis of the compounds of this disclosure, which contain p-methane-3,8-diol as an active ingredient. [Figure 3] This is a reaction scheme for the synthesis of the compounds of this disclosure, which contain minoxidil as an active ingredient. [Figure 4] This is a reaction scheme for the synthesis of the compounds of this disclosure, which contain deslotalazine as an active ingredient. [Figure 5] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 6A]UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 6B] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 6C] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 6D] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 7] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 8] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 9] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 10] This figure shows the adhesion of the compounds of this disclosure to pig skin. [Figure 11] UV spectra of compounds containing a 3,4-dihydro-2H-pyran moiety (some of which are compounds according to this disclosure) and UV spectra of their corresponding lysine conjugates. [Figure 12] This figure shows the adhesion of the compounds of this disclosure to pig skin. [Modes for carrying out the invention] 【0047】 In a first aspect, the disclosure relates to a compound that can be covalently bonded to the skin, particularly a compound included in a topical composition further comprising an excipient suitable for topical administration, wherein the compound that can be covalently bonded to the skin is a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts. 【0048】 [ka] 【0049】 The term “compounds that can covalently bond to the skin” is applied in its general sense in the art, and in particular refers to compounds that can undergo a chemical reaction to covalently bond to the amino side chain of an amino acid, such as lysine. Additionally or alternatively, a compound is “covalently bondable to the skin” if, after incubation of the compound (or a topical composition containing the compound) on pig skin at 37°C for 24 hours, the compound (or a topical composition containing the compound) cannot be completely washed off the (explanted) pig skin with water, soap, and / or isopropanol. Additionally or alternatively, a compound is “covalently bondable to the skin” if, when 0.1 mol / L of the compound is placed in an aqueous solution having a pH of approximately 5 and further containing 0.1 mol / L of lysine at 37°C for 24 hours, the compound is converted to more than 10 mol% of its corresponding 1,4-dihydropyridine derivative. 【0050】 The features in the above paragraph explicitly refer to “skin,” but the term “topical composition” should not be interpreted as excluding compositions formulated / intended for (or primarily or even exclusively for) other skin appendages. Skin appendages are components derived from the epidermis and dermis of the skin, including hair, nails, sweat glands, and sebaceous glands. 【0051】 In the compound of formula (I), R 1This refers to a protecting group that is hydrolyzable under physiological conditions after application of a topical composition to hydrogen or the skin. When “physiological conditions” is used in this context, it should be understood that this specifically refers to the pH conditions encountered at the site where the compound of formula (I) is expected to bind, for example, to the object being treated (skin or skin appendages). Additionally or alternatively, the term “protecting group that is hydrolyzable under physiological conditions after application of a topical composition” refers to a group that is hydrolyzed when a 0.1 mol / L compound of formula (I) is placed in an aqueous solution with a pH of approximately 5 for 24 hours, and the group in question is eligible as “protecting group that is hydrolyzable under physiological conditions after application of a topical composition” if more than 10 mol% of it is converted to its corresponding hemiacetal. 【0052】 A1, A2, and A3 are independent of each other. a) Group: C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) Group: C1~C 60 It represents a part or polymer portion. 【0053】 b) C1~C 60 The partial or polymer portion carries the active ingredient / active ingredient. Therefore, at least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part. 【0054】 b) C1~C 60 The partial or polymer portion is subdivided into two subgroups b1) and b2). C1-C of group b1) 60 The partial or polymer portion is configured to act as a skin moisturizer, insecticide, skin whitening agent, or pharmaceutical. In other words, the active ingredient / active ingredient can provide its activity while bound to the rest of the 3,4-dihydro-2H-pyran portion. b2) C1-C 60The partial or polymer portion is configured to act as a skin moisturizer, insecticide, skin whitening agent, fragrance, or pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. In other words, the active ingredient / active ingredient may provide its activity after being released from the rest of the 3,4-dihydro-2H-pyran moiety. In some cases, for example, in the case of a fragrance, the bound active ingredient is active only after release, but the two subgroups b1) and b2) are not necessarily mutually exclusive. For example, a polyol humectant may provide its moisturizing activity not only while bound to the 3,4-dihydro-2H-pyran moiety, but also when released from the 3,4-dihydro-2H-pyran moiety. 【0055】 C1~C of group b2) which are cleaved (released) from the 3,4-dihydro-2H-pyran moiety 60 Where referring to a portion or polymer portion, it should be understood that this refers to the 3,4-dihydro-2H-pyran portion including (or at least partially including) L1, L2 and / or L3 (if present) and any remaining A1-A3 portions. Furthermore, it should be understood that this refers to the cleavage (or release) of the compound under physiological conditions encountered after application of the topical composition to the skin (or skin appendages). Where referring to “physiological conditions” in this context, it should be understood that this specifically refers to the ambient conditions, particularly pH conditions, enzymatic conditions and temperature conditions, encountered at the site where the compound of formula (I) is thought to bind, for example, to the keratinous tissue of the stratum corneum and / or epidermis of the subject being treated (mammalian, especially human). Additionally or alternatively, C1-C of group b2) are cleaved from the 3,4-dihydro-2H-pyran portion. 60 The performance of the partial or polymer portion can be evaluated in an in vitro porcine skin model at 37°C. 【0056】 As described above, the 3,4-dihydro-2H-pyran derivatives of this disclosure are selected such that the formation of a conjugated π-electron system with respect to the 1,4-dihydropyridine moiety bound to the skin is essentially avoided. Accordingly, the compounds of this disclosure are limited such that L1-A1 and L2-A2 do not represent moieties containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. 【0057】 A1, A2, and A3 are independent of each other, C1~C 30 The term may also refer to a part, i.e., a part made up of group a). This term is not particularly limited beyond its general understanding in the art and refers to any part containing 1 to 30 carbon atoms. The presence of further heteroatoms, i.e., atoms other than C, is not excluded, i.e., atoms such as H, O, and N may be included in the part. 【0058】 A1, A2, and A3 are independent of each other, C1-C of group b1) and / or group b2). 60 This may represent a part or a polymer part. Here too, C1~C 60 The term "part" is not particularly limited beyond its general understanding in the art and refers to any part containing 1 to 60 carbon atoms. The presence of further heteroatoms, i.e., atoms other than C, i.e., atoms such as H, O, and N, is not excluded. 60 It may be included in the part. Furthermore, the term “polymer part” is not particularly limited beyond its general understanding in the art and refers to any oligomeric part (defined herein as having 4 to 8 repeating units) or polymer part (defined herein as having 9 or more repeating units). The polymer part, i.e., the polymer, will typically contain carbon and / or silicon, but the presence of further heteroatoms, i.e., atoms other than C or Si, is not excluded, i.e., atoms such as H, O, N and others may be included in the polymer part. 【0059】 A1, A2, and A3 are configured to act independently as skin moisturizers, insecticides, skin whitening agents, or pharmaceuticals, in group C1-C of b1). 60 It may represent a part or a polymer part. The functional group term is C1-C 60 This implies that a portion or polymer portion (or more specifically, the entire compound after covalent bonding to a keratinous substance such as skin) can provide the effects mentioned (skin moisturizing effect, insecticidal effect, skin whitening effect, or medicinal effect). 【0060】 A1, A2, and A3 are configured to act independently as skin moisturizers, insecticides, skin whitening agents, fragrances, or pharmaceuticals after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b2) 60 It may represent a part or a polymer part. The functional group term is C1-C 60 This implies that the compound released from a portion or polymer portion (or more specifically, from the entire compound after covalent bonding to a keratinous substance such as skin) can provide the mentioned effects (skin moisturizing effect, insecticidal effect, skin whitening effect, olfactory effect, or medicinal effect) after cleavage from the 3,4-dihydro-2H-pyran portion. 【0061】 In some embodiments, A1, A2, and A3 may represent polymer moieties of group b1) or group b2) that are independently configured to act as skin moisturizers. The functional group terminology implies that the polymer moiety (or more specifically, the entire compound after covalent bonding to a keratinous substance such as skin) can provide a skin moisturizing effect. 【0062】 The term "skin moisturizer" refers to a compound / part that can directly bond with water in the skin (via hydrogen bonds) or reduce the evaporation of water from the skin. Therefore, this term encompasses moisturizers, emollients, and evaporation inhibitors, as used and understood in the art. 【0063】 The term "insecticide" refers to its general meaning in the art, and in particular to compounds that can kill, incapacitate, repel, or otherwise improve risks to the health, comfort, or welfare of mammals (humans) posed by invertebrates, especially insects. 【0064】 The term "skin whitening agent" refers to the general meaning in the relevant technical field, and in particular to compounds that can lighten skin tone chemically and / or metabolically. The term "skin whitening agent" does not refer to pigments, dyes, or fluorescent whitening agents. 【0065】 The term "fragrance" refers to its general meaning in the art, and more specifically to volatile compounds that can provide an olfactory impression, particularly one or more of the seven basic scents (floral, fruity, minty, nutty, pungent, sweet, and woody). 【0066】 The term "pharmaceutical" refers to its general meaning in the art, and in particular to compounds that are available for / intended to be used in the diagnosis, cure, alleviate, treat, cure, or prevent diseases in mammals, especially humans, as well as domesticated animals and livestock. 【0067】 L1, L2, and L3 independently represent a linker group or are absent. The term “linker group” is not particularly limited and refers to any chemical group that covalently bonds the 3,4-dihydro-2H-pyran moiety to the corresponding moieties A1, A2, and A3, respectively. For clarity, it should be understood that L1 and L2 are bonded to the 3,4-dihydro-2H-pyran moiety by a single bond, i.e., the ring positions marked “a” and “b” represent methine (“CHR3”). 【0068】 In some embodiments, L1, L2, and L3, if present, independently represent an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with their optionally chosen substituents. 【0069】 In some embodiments, L1, L2, and L3 may also optionally form cyclic structures. In some embodiments, L1 and L2 are present and form 5-membered, 6-membered, 7-membered, or 8-membered rings, particularly cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl. 【0070】 In some embodiments, L1 and L2 form optionally substituted five-membered or six-membered rings, and together with their substituents, contain 2 to 14 carbon atoms, more specifically 3 to 12, and particularly 4 to 8 carbon atoms. For clarity, it should be understood that when L1 and L2 form five-membered or six-membered rings, two of the ring carbons originate from the 3,4-dihydro-2H-pyran moiety and are therefore not counted in relation to the total number of carbon atoms in L1 and L2. Two examples are given: When L1 and L2 form tetrahydrofuranyl, the number of carbon atoms is 2. When L1 and L2 form cyclopentyl monosubstituted with a -CH2-OH group, the number of carbon atoms is 4. 【0071】 In some embodiments, L1 and L2 exist, and A1 and A2 are -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4-It may be particularly advantageous to form an optionally substituted five-membered or six-membered ring, especially cyclopentyl or cyclohexyl, which is bonded via optionally selected groups from -, or combinations thereof. In some embodiments, L1 and L2 are present, and A1 and A2 are -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 -It is most advantageous to form a cyclopentyl ring, cyclopentenyl ring, cyclohexyl ring, or cyclohexenyl ring, which is bonded via a group selected from combinations thereof or optionally. 【0072】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (II), 【0073】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 L3, A1, and A3 are defined as for the compound of formula (I), (R 2 ) n Each represents n parts independently selected from H, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, amino, or halogen. n is an integer selected from 1 and 2. L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-, -O-(CH2) 1~4 -or a base selected from a combination thereof, R 4This is selected from H or C1-C4 alkyl. 【0074】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (III), 【0075】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 L3, A1, and A3 are defined as for the compound of formula (I), L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-, -O-(CH2) 1~4 -or a base selected from a combination thereof, R 4 This is selected from H or C1-C4 alkyl. 【0076】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (IV), 【0077】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 And A1 is as follows for the compound of formula (I): (R 2 ) n Each represents n parts independently selected from H, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, amino, or halogen. n is an integer selected from 1 and 2. L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR4 -,-NR 4 -C(O)-,-C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-,-O-(CH2) 1~4 - or any one of the groups selected from combinations thereof, R 3 represents hydrogen or an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with an optional substituent, R 4 is selected from H or C1-C4-alkyl. 【0078】 In some embodiments, the compound capable of covalently binding to the skin is a compound of formula (V), 【0079】 【Chemical formula】 or a tautomer and / or pharmaceutically acceptable salt thereof, wherein R 1 and A1 are as defined for the compounds of formula (I), L4 is absent or is a group selected from -O-,-S-,-C(O)-,-CO2-,-O-C(O)-,-NR 4 -,-NR 4 -C(O)-,-C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-,-O-(CH2) 1~4 - or any one of the groups selected from combinations thereof, R 3 represents hydrogen or an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with an optional substituent, R 4 is selected from H or C1-C4-alkyl. 【0080】 The usefulness of the compounds of this disclosure is illustrated by the following examples. Of course, other uses are readily apparent to those skilled in the art based on the guidelines provided in this disclosure and are routinely available. 【0081】 The first example relates to a compound intended to provide a moisturizing effect. Skin moisturizers are well established in cosmetics and include a wide variety of compounds that can bind water in the stratum corneum. Examples include polyols such as glycerol, pentaerythritol, and sorbitol, as well as other hydrogen-bonding compounds such as urea. b) C1-C 60 Compounds according to this disclosure that have pentaerythritol as a part are shown below. 【0082】 [ka] 【0083】 Genipin derivatives are well known to bind to the stratum corneum. Due to their high hydroxyl group content, the compounds according to the present invention are expected to provide long-lasting moisturizing effects to the skin. Even if the pentaerythritol portion remains bound to the skin via the 3,4-dihydro-2H-pyran portion, a moisturizing effect will still be obtained. Therefore, this portion is an example of group b1). In addition, the ester group linking the pentaerythritol portion to the rest of the compound is cleavable by esterases, which are abundant on the skin. Therefore, it is also an example of a portion that simultaneously belongs to group b2). If it is desirable that the pentaerythritol portion belongs only to group b1), another functional group may be selected. For example, one might consider replacing the ester bond with an ether bond. 【0084】 Figure 1 shows a schematic of the chemical synthesis of the above compounds. The synthesis of compounds (1) and (2) is disclosed in concurrently pending international application No. 2023 / 102652(A1). Compound (2) can be converted to the corresponding acyl chloride by thionyl chloride, which is then combined with pentaerythritol to obtain ester (3). Ester (3) can be hydrolyzed by gentle heating in an acidic aqueous solution to obtain the target compound (4). 【0085】 In the experimental section, we demonstrate that the humectant glycerol and the emollient decanol can be conjugated to a hydrogenated genipine derivative, and that the resulting conjugate can be attached to the skin. Specifically, the following compounds were synthesized and attached to the skin. 【0086】 [ka] 【0087】 The second example relates to a compound intended to provide an insecticidal effect, more specifically an insect repellent effect. 【0088】 Para-menthane-3,8-diol (PMD) is an insect repellent that can be used directly on skin or clothing. It is colorless and has broad efficacy against various arthropods such as mosquitoes, mites, gnats, flies, and fleas. The chemical structure of PMD is reproduced below. 【0089】 [ka] 【0090】 The insect repellent efficacy of PMD is comparable to that of N,N-diethyl-m-methylbenzamide (DEET). However, like DEET, PMD only provides a short-lasting effect of up to 6-8 hours. This is mainly due to PMD's relatively high volatility. 【0091】 Efforts continue to increase the retention time of PMDs on the skin. Particularly interesting, recent research has revealed that PMDs can be retained in the stratum corneum for up to 5 days by chemically conjugating them to acrylic copolymers applied topically to the skin (Shah, SI et al., Pharmaceuticals 2021, 13, 403). More specifically, the authors demonstrated that acryloyl chloride can form a conjugate with the secondary alcohol of PMD via ester bonding, and that the resulting conjugated monomer can crosslink to copolymers containing the PMD conjugate. The authors further demonstrated that esterases can release PMDs from the copolymer in ex vivo tests and in vitro tests when the copolymer was applied to porcine skin. 【0092】 Therefore, compounds of this disclosure containing PMDs bonded to the rest of the molecule via ester groups are suitable candidates for sustained-release of PMDs to the skin. Specific exemplary compounds are listed below. 【0093】 [ka] 【0094】 Figure 2 shows a schematic of the chemical synthesis of the above compounds. The synthesis of compounds (1) and (2) is disclosed in concurrently pending international application No. 2023 / 102652(A1). Compound (2) can be converted to the corresponding acyl chloride by, for example, thionyl chloride, which is then combined with PMD to obtain ester (3). Ester (3) can be hydrolyzed by gentle heating in an acidic aqueous solution to obtain the target compound (4). 【0095】 As supported by the paper Shah, SI et al, Pharmaceuticals 2021, 13, 403, the ester group linking PMD to the rest of the compound can be expected to be cleaved by skin esterases, and PMD is released into the stratum corneum over time to provide its insect repellent effect. 【0096】 In the experimental section, we demonstrate that the insecticide picaridin can be conjugated to a genipine hydrogenate derivative, and that the resulting conjugate can be conjugated onto the skin. Specifically, the following compounds were synthesized and conjugated onto the skin. 【0097】 [ka] 【0098】 The third example relates to a compound intended to provide a pharmaceutical effect, more specifically, the treatment / prevention of alopecia. 【0099】 Minoxidil and its derivatives, such as copexil, are applied topically to treat alopecia. Minoxidil is typically applied to the scalp twice daily in an alcohol solution (ethanol and propylene glycol). While this compound generally shows good tolerability, common side effects include dandruff and contact dermatitis caused by frequent exposure to ethanol and propylene glycol, which dry out the scalp. Therefore, a topical delivery system requiring less frequent application of minoxidil is desirable to minimize side effects and improve patient compliance. 【0100】 Minoxidil has the following chemical structure. 【0101】 [ka] 【0102】 A paper by Stoica et al. (Bioorganic & Medicinal Chemistry Letters, 2016, 26(4), 1145-1150) provides a convenient method for conjugating minoxidil to alcohol via activation of the compound with N,N-carbonyldiimidazole (CDI). This synthetic route allows for easy access to the following compounds of this disclosure. 【0103】 [ka] 【0104】 A schematic of the chemical synthesis of the above compounds is shown in Figure 3. The synthesis of compound (3) is disclosed in concurrently pending international application No. 2023 / 102652(A1). Minoxidil (1) is activated with CDI to obtain compound (2), which is then reacted with (3) to obtain carbamate (4). (4) is hydrolyzed while being gently heated in an acidic aqueous solution to obtain a target compound (5) to which minoxidil is bonded to the rest of the compound via a monosubstituted carbamate group. 【0105】 Monosubstituted carbamate groups are frequently used in prodrugs and can be cleaved by esterases (see review by Gosh et al., J. Med. Chem., 2015, 58, 7, 2895-2940). Therefore, the above compounds are promising candidates for providing sustained release of minoxidil to the skin. 【0106】 The fourth embodiment also relates to a compound intended to provide a pharmacokinetic effect, more specifically, the treatment of an allergic condition. 【0107】 Desloratadine, or the metabolically active form of loratadine, is a very potent antihistamine, administered orally once daily at a dose of 5 mg. Topical formulations of desloratadine are currently being studied. Mohamed et al., Pharmaceuticals 2023, 16(4), 578, describe desloratadine as having good penetration through the skin when applied as a transdermal gel formulation. The authors found that the gel formulation has higher bioavailability and is excreted more slowly than the tablet formulation. The bioavailability of the gel formulation was 2.4 to 3.2 times that of the tablet formulation. This means that a very low daily dose of desloratadine of about 2 mg may be sufficient to provide adequate anti-allergic effects, which makes desloratadine even more attractive as a pharmacopoeia for the compound of this disclosure, as systemic side effects associated with oral administration of desloratadine may be reduced. 【0108】 Desloratadine has the following chemical structure: 【0109】 [ka] 【0110】 A schematic of the chemical synthesis of the above compounds is shown in Figure 4. The synthesis of compound (2) is disclosed in concurrently pending international application No. 2023 / 102652(A1). Desloratadine (1) is combined with CDI to form compound (2) and obtain carbamate (3). Compound (3) is hydrolyzed while being gently heated in an acidic aqueous solution to obtain target compound (4), to which desloratadine is bonded to the rest of the compound via an N,N-disubstituted carbamate group. This synthetic route provides easy access to the following compounds of this disclosure. 【0111】 [ka] 【0112】 The N,N-disubstituted carbamate group used in the above compound is frequently used in prodrugs (e.g., vanbuterol) and can be cleaved by esterases to exhibit relatively long-term sustained release (see review by Gosh et al., J.Med.Chem., 2015, 58, 7, 2895-2940). Therefore, the above compound is a promising candidate for providing long-term release of desloratadine into the skin. Thus, a long-lasting depot effect can be expected, potentially enabling less frequent administration, especially, for example, once a week. In practice, this can be done by applying a transdermal patch overnight that transfers and fixes the desloratadine-containing compound into the skin. From the transdermal patch, desloratadine is released by enzymatic activity in the skin over a period of, for example, one week. 【0113】 As can be seen from the above examples, the compounds of this disclosure offer broad utility and versatility when applying the active ingredient topically to keratin tissue. 【0114】 Further aspects, features, and embodiments of this disclosure are described below. 【0115】 In some embodiments, b) C1-C 60 The part or polymer part is its C1-C 60 The partial or polymer portion may contain a functional group that is bonded to the corresponding L1, L2, or L3 portion, or, if the corresponding L1, L2, or L3 portion is absent, to the 3,4-dihydro-2H-pyran portion. 【0116】 In some embodiments, the functional group may include a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, or a combination thereof, more specifically, a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof, in particular a carbon atom and / or an oxygen atom. 【0117】 In some embodiments, the functional group may include one or more, two or more, three or more, four or more, or all of the following: 1 to 12 carbon atoms, more specifically 1 to 6 carbon atoms, in particular 1 to 3 carbon atoms; 1 to 12 oxygen atoms, more specifically 1 to 6 oxygen atoms, in particular 1 to 3 oxygen atoms; 1 to 4 nitrogen atoms, more specifically 1 to 3 nitrogen atoms, in particular 1 to 2 nitrogen atoms; 1 to 3 sulfur atoms, more specifically 1 to 2 sulfur atoms, in particular 1 sulfur atom; and 1 to 3 phosphorus atoms, more specifically 1 to 2 phosphorus atoms, in particular 1 phosphorus atom. 【0118】 In some embodiments, the functional group may be cleavable under physiological conditions after the topical composition has been applied to the skin. When “physiological conditions” is referred to in this context, it should be understood that this refers in particular to the pH conditions encountered at sites where the compound of formula (I) is thought to bind, for example, to keratinous tissue in the stratum corneum and / or epidermis of the subject being treated (mammalian, particularly human). In some embodiments, the functional group may be hydrolyzable at the physiological pH of mammalian skin, more specifically human skin, particularly a pH of about 5 to about 6. A preferred in vitro test is to place a 0.1 mol / L compound of formula (I) in an aqueous solution having a pH of about 5 at 37°C for 24 hours, and the group of interest is considered hydrolyzable if a significant amount of the group is hydrolyzed (e.g., more than 5 mol% or more than 10 mol%). 【0119】 In some embodiments, the functional group may be enzymatically cleavable under physiological conditions after application of the topical composition to the skin, particularly by enzymes present in human skin. When “physiological conditions” is referred to in this context, it should be understood that this refers specifically to the conditions encountered at sites where the compound of formula (I) is thought to bind, for example, to keratinous tissue in the stratum corneum and / or epidermis of the subject being treated (mammalian, particularly human). A preferred in vitro test involves placing a 0.1 mol / L solution of the compound of formula (I) in an aqueous solution having a pH of about 5 and further containing 50 U of esterase activity at 37°C for 24 hours, and the group of interest is considered enzymatically cleavable if a significant amount of the group is cleaved (e.g., more than 5 mol% or more than 10 mol%). 【0120】 In some embodiments, the functional group may be configured to be cleaved into a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonate, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefin, an olefin, or an oxime, or a salt thereof. 【0121】 In some embodiments, the functional group is a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonate, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefin, or an oxime, or a salt thereof, from group b) C1-C 60 The system may be configured to provide the 3,4-dihydro-2H-pyran portion after cleavage if the corresponding L1, L2, or L3 portion is not present or bonded to the partial or polymer portion. 【0122】 In some embodiments, the functional group is a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonate, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefin, or an oxime, or a salt thereof, after cleavage, C1-C of group b) 60It may be configured to provide a portion or a polymer portion. 【0123】 In some embodiments, the functional group may include carbon esters, particularly monoesters, 1,1-diesters, carbonates, or carbamates; ethers or thioethers, particularly acetals, hemiacetals, glycoside groups, or thioacetals; carbon amides, particularly peptides or N-Mannich bases; enols; enamines; imines; oximes; sulfate esters; sulfonic acid esters; sulfonic acid amides; phosphate esters; phosphonic acid esters; phosphate amides; or phosphonic acid amides. 【0124】 In some embodiments, the functional group is described in the textbook Prodrug Design Perspectives, Approaches and Applications in Medicinal Chemistry, 1 st These may also be functional groups described in Chapter 6 of ed., 2015, ISBN: 9780128035191, which are incorporated herein by reference (for the purposes described above, and in whole). 【0125】 In some embodiments, A1 is C1-C of group b). 60 It may represent a part or polymer part. Additionally or alternatively, A2 is C1-C of group b). 60 It may represent a part or polymer part. Additionally or alternatively, A3 is C1-C of group b). 60 It may represent a part or polymer part. Additionally or alternatively, the remainder of A1, A2 and A3 may be substituents of group a), more specifically C1-C 30 It may represent a partial, H, hydroxyl, amino, or halogen. 【0126】 In some embodiments, L1 is present and represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optionally chosen substituent. Alternatively or additionally, in some embodiments, L2 may be present and represent an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optionally chosen substituent. Alternatively or additionally, in some embodiments, L3 may be present and represent an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optionally chosen substituent. 【0127】 In some embodiments, L1 may be present and may, in combination with its optional substituent, represent an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms, and the functional group may be bonded to L1. Alternatively or additionally, in some embodiments, L2 may be present and may, in combination with its optional substituent, represent an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms, and the functional group may be bonded to L2. Alternatively or additionally, in some embodiments, L3 may be present and may, in combination with its optional substituent, represent an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms, and the functional group may be bonded to L3. In some embodiments, if any of L1 to L3 are (also) optionally substituted with heteroatoms, each linker group may contain 1 to 8, more specifically 1 to 6, in particular 1 to 4 oxygen atoms; 1 to 8, more specifically 1 to 6, in particular 1 to 4 nitrogen atoms; 1 to 6, more specifically 1 to 4, in particular 1 to 3 sulfur atoms; 1 to 6, more specifically 1 to 4, in particular 1 to 3 phosphorus atoms; and 1 to 10, more specifically 1 to 8, in particular 1 to 6 halogen atoms. In some embodiments, each linker group contains no further atomic species other than carbon, (optionally) the aforementioned atomic species and hydrogen. 【0128】 In some embodiments, L1 and L2 may be present, and A1 and A2 are -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2) 1~4 -,-(CH2) 1~4 -O and -O-(CH2) 1~4 - May be bonded via a group selected from -, forming an optionally substituted five-membered or six-membered ring, particularly cyclopentyl or cyclohexyl. It should be understood that the aforementioned specific groups may also be part of a larger functional group, and are therefore referred to as “combinations thereof.” For example, carbamates can be thought of as either -O and -C(O)-NH or combinations thereof. 【0129】 In some embodiments, L1 and L2 may be present, and A1 and A2 are -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2) 1~4 -,-(CH2) 1~4 -O and -O-(CH2) 1~4 -A cyclopentyl ring, cyclopentenyl ring, cyclohexyl ring, or cyclohexenyl ring may be formed by optionally bonding a group selected from -O, or a combination thereof. It should be understood that the aforementioned specific groups may also be part of a larger functional group, and are therefore referred to as “combinations thereof.” For example, carbamates can be thought of as both -O and -C(O)-NH or a combination thereof. 【0130】 In some embodiments, A1 is C1-C of group b). 60 It may be a part or a polymer part. In some embodiments, A3 is C1-C of group b). 60 It may be a part or a polymer part. In some embodiments, and in particular in the two embodiments described above, A2 is a substituent of group a), more specifically C1-C 30 It may represent a partial, H, hydroxyl, amino, or halogen, especially hydrogen. 【0131】 In some embodiments, A1 is C1-C of group b). 60 They may be a part or a polymer part. In some embodiments, A2 and A3 are substituents of group a), more specifically independently of each other, C1-C 30 It may represent a partial, H, hydroxyl, amino, or halogen, especially hydrogen. 【0132】 In some embodiments, A1 is C1-C of group b). 60 It may be a part, and A2 and A3 are substituents of group a), more specifically, C1~C independently of each other. 30 It may represent a part, H, hydroxyl, amino, or halogen, and especially hydrogen. 【0133】 In some embodiments, a) C1-C 30 The part may contain 1 to 30, more specifically 1 to 16, in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, in particular 0 to 3 phosphorus atoms; and 0 to 10, more specifically 0 to 8, in particular 0 to 6 halogen atoms. 【0134】 In some embodiments, C1~C 30 The part may be selected from saturated or unsaturated, cyclic or acyclic (hetero)alkyl groups containing 1 to 30, more specifically 1 to 16, in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, in particular 0 to 6 halogen atoms, and / or C1 to C 30 The portions may be bonded to L1, L2, and L3, respectively, via carbon atoms, oxygen atoms, nitrogen atoms, or sulfur atoms. 【0135】 In some embodiments, A3 is C1-C of group a) 30 A selection of saturated or unsaturated cyclic or acyclic (hetero)alkyl C1-C2 atoms, comprising a portion, more specifically 1-16, more specifically 1-12, and especially 1-8 carbon atoms; 0-6, more specifically 0-4, and especially 0-3 oxygen atoms; 0-6, more specifically 0-4, and especially 0-3 nitrogen atoms; 0-6, more specifically 0-4, and especially 0-3 sulfur atoms; and 0-6, more specifically 0-4, and especially 0-3 halogen atoms. 16 It may also represent a part. 【0136】 In some embodiments, A3 is C1-C selected from carboxylic acids or their salts; carboxylic acid esters; or ketones. 16 It may also represent a part. 【0137】 In some embodiments, A3 is a C1-C4 alkyl carboxylic acid or its salt; a C1-C4 alkyl carboxylic acid ester; or a C1-C4 alkylcarbonyl selected from C1-C4 alkylcarbonyl. 16 It may also represent a part. 【0138】 In some embodiments, L1 and OR 1 These may combine with the carbon atoms to which they are bonded to form a five-membered or six-membered lactone. 【0139】 In some embodiments, R1 is hydrogen, C 1~6 Acyl or C 1~6 It may represent an alkyl group. In some embodiments, it may be particularly advantageous for R1 to represent H. In some embodiments, it may be particularly advantageous for R1 not to represent a glucoside. 【0140】 In some embodiments, at least one of A1, A2, and A3 is C1-C of group b1). 60 It may represent a part. In some embodiments, at least one of A1 and A2 is C1-C of group b1). 60 It may also represent a part. 【0141】 In some embodiments, at least one of A1, A2, and A3 is C1-C of group b2). 60 It may represent a part or polymer part. In some embodiments, at least one of A1 and A2 is C1-C of group b2). 60 It may represent a portion or a polymer portion. 【0142】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (II), 【0143】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 L3, A1 and A3 are as defined in any prior embodiment, (R 2 ) n Each represents n parts independently selected from H, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, amino, or halogen. n is an integer selected from 1 and 2. L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-, -O-(CH2) 1~4 - or a base selected from a combination thereof, R 4 This is selected from H or C1-C4 alkyl. 【0144】 In some embodiments of formula (II), at least one of A1 and A3 is C1-C of group b) 60 It may represent a part or a polymer part. In some embodiments of formula (II), at least A1 is C1-C of group b). 60It may represent a part or a polymer part. In some embodiments of formula (II), A3 is C1-C of group a) 30 A selection of saturated or unsaturated cyclic or acyclic (hetero)alkyl C1-C2 atoms, comprising a portion, more specifically 1-16, more specifically 1-12, and especially 1-8 carbon atoms; 0-6, more specifically 0-4, and especially 0-3 oxygen atoms; 0-6, more specifically 0-4, and especially 0-3 nitrogen atoms; 0-6, more specifically 0-4, and especially 0-3 sulfur atoms; and 0-6, more specifically 0-4, and especially 0-3 halogen atoms. 16 It may also represent a part. 【0145】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (III), 【0146】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 L3, A1 and A3 are as defined in any prior embodiment, L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-, -O-(CH2) 1~4 - or a base selected from a combination thereof, R 4 This is selected from H or C1-C4 alkyl. 【0147】 In some embodiments of formula (III), at least one of A1 and A3 is C1-C of group b). 60 It may represent a part or a polymer part. In some embodiments of formula (III), at least A1 is C1-C of group b). 60It may represent a part or a polymer part. In some embodiments of formula (III), A3 is C1-C of group a) 30 A selection of saturated or unsaturated cyclic or acyclic (hetero)alkyl C1-C2 atoms, comprising a portion, more specifically 1-16, more specifically 1-12, and especially 1-8 carbon atoms; 0-6, more specifically 0-4, and especially 0-3 oxygen atoms; 0-6, more specifically 0-4, and especially 0-3 nitrogen atoms; 0-6, more specifically 0-4, and especially 0-3 sulfur atoms; and 0-6, more specifically 0-4, and especially 0-3 halogen atoms. 16 It may also represent a part. 【0148】 In some embodiments of formula (III), L3 represents -C(O)-, -C(O)-O-, -C(O)-NH-, or -C(O)-N(C1~C4-alkyl)-. 【0149】 In some embodiments of formula (III), A3 is R 3 Represents the base, R 3 C1-C12 includes 1-14, more specifically 1-12, and especially 1-8 carbon atoms; 0-12, more specifically 0-8, and especially 0-6 oxygen atoms; 0-8, more specifically 0-6, and especially 0-4 nitrogen atoms; 0-6, more specifically 0-4, and especially 0-3 sulfur atoms; and 0-10, more specifically 0-8, and especially 0-6 halogen atoms. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups is R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0150】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (IV), 【0151】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 And A1 are as defined in any prior embodiment, (R 2 ) nEach represents n parts independently selected from H, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, amino, or halogen. n is an integer selected from 1 and 2. L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O-, -O-(CH2) 1~4 - or a base selected from a combination thereof, R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R 4 This may be selected from H or C1-C4 alkyl groups. 【0152】 In some embodiments of formula (IV), A1 is C1-C of group b). 60 It may represent a part or a polymer part. In some embodiments of formula (IV), A1 is C1-C of group b). 60 It may also represent a part. 【0153】 In some embodiments of equation (IV), R 3 R represents a composition or compound according to any one of the prior claims, comprising 1 to 14, more specifically 1 to 12, particularly 1 to 8 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms, which are optionally substituted phenyl. 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups is R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0154】 In some embodiments of equation (IV), R 3 This may represent a C1-C4 alkyl group or a phenyl group. 【0155】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (V), 【0156】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 And A1 are as defined in any prior embodiment, L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 , -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - or a base selected from a combination thereof, R 3 represents the C1-C4 alkyl portion or phenyl, or R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or any substituent thereof. R 4 This is selected from H or C1-C4 alkyl. 【0157】 In some embodiments of formula (V), A1 is C1-C of group b). 60 It may represent a part or a polymer part. In some embodiments of formula (V), A1 is C1-C of group b). 60 It may also represent a part. 【0158】 In some embodiments of equation (V), R 3R represents a composition or compound according to any one of the prior claims, comprising 1 to 14, more specifically 1 to 12, particularly 1 to 8 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms, which are optionally substituted phenyl. 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0159】 The following discusses the active component bound to the rest of the compound according to the present invention. For simplicity of explanation, the active component will be referred to as if it were an individual compound, rather than a portion bound to the rest of the compound. It should be understood that this should be interpreted as referring to the portion bound to the rest of the compound, for example, the removal of a hydrogen atom from the active component. 【0160】 Furthermore, it should be understood that the following disclosures relating to the active ingredients can be freely combined with the above disclosures relating to the compounds of formulas (I) to (V). In fact, these combinations represent preferred embodiments of the present disclosure, but it should be understood that the present disclosure is not limited to them. 【0161】 Compounds that act as skin moisturizers In some embodiments, at least one of A1, A2, and A3 is configured to act as a skin moisturizer and / or to act as a skin moisturizer after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 It may be a part or a polymer part. 【0162】 In some embodiments, C1~C 60 The partial or polymer portion may contain a plurality of hydrogen bonding groups selected from the group consisting of hydroxyl groups, ether groups, carboxylic acids, amines and amides, and salts thereof. 【0163】 In some embodiments, the hydrogen bonding groups may include three or more, more specifically four or more, and particularly six or more hydrogen bonding groups. 【0164】 In some embodiments, C1~C 60 The ratio of the total number of hydrogen bonding groups in the portion to the total number of hydrogen bonding groups may be approximately 4:1 to 1:1, more specifically approximately 3:1 to 1:1, and especially approximately 2:1 to 1:1. 【0165】 In some embodiments, C1~C 60 The portion may have a molecular weight of at least 60 g / mol, more specifically at least 90 g / mol, and in particular at least 120 g / mol. 【0166】 In some embodiments, the polymer portion may have a molecular weight in the range of 200 to 50,000 g / mol. 【0167】 In some embodiments, C1~C 60 The ratio of heteroatoms in the part to the total number of heteroatoms may be approximately 4:1 to 1:2, more specifically approximately 3:1 to 1:1.5, and especially approximately 2:1 to 1:1, with the heteroatoms being selected from nitrogen and oxygen. 【0168】 In some embodiments, C1~C 60 The part or polymer part is Polyols, more specifically, polyols having n hydroxyl groups where n is 2 or greater, 3 or greater, 4 or greater, 5 or greater, 6 or greater, 8 or greater, 10 or greater, 12 or greater, or 16 or greater; Monovalent or polyvalent carboxylic acids containing one or more hydroxyl groups, more specifically, glycolic acid, lactic acid, malic acid, tartaric acid, or citric acid; Sugars, more specifically trioses, tetroses, pentoses, hexoses, monosaccharides, disaccharides, trisaccharides, oligosaccharides, or polysaccharides, especially glucose, mannose, galactose, glucosamine, N-acetyl-D-glucosamine, myo-inositol, rhamnose, lyxose, fucose, allose, ribose, arabinose, hyaluronic acid, especially hyaluronic acid having a molecular weight of less than 50,000 daltons; Sugar alcohols, more specifically sugar alcohols containing 2 to 24 carbon atoms, in particular ethylene glycol, propylene glycol, glycerol, erythritol, treitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, boremitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; or The material may include sugar acids, more specifically aldonic acid, urosonic acid, uronic acid, or aldaric acid; or salts thereof; or esters thereof, especially C1-C4 alkyl esters thereof; or amides thereof. 【0169】 In some embodiments, C1~C 60 The portion may include urea derivatives; panthenol; or diuretics, particularly allantoin. 【0170】 In some embodiments, C1~C 60 The partial or polymer portion may contain an amino acid or an amino acid derivative, more specifically, serine, glycine, alanine, histidine, ornithine, arginine, or pyroglutamic acid. In some embodiments, the amino acid may be present in its L-enantiomer. In some embodiments, C1-C 60 The partial or polymer portion may contain multiple amino acids or amino acid derivatives. 【0171】 In some embodiments, C1~C 60 The portion may have a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and particularly 120 g / mol to 1200 g / mol. 【0172】 In some embodiments, b) C1-C 60 The partial or polymer portion is aliphatic C 10 ~C 60 Part, more specifically C 15 ~C 60 aliphatic portion, especially C 20 ~C60 The aliphatic portion may also be included; or it may contain an oligosiloxane or polysiloxane, particularly a poly(di-C1~C4-alkyl)siloxane. 【0173】 In some embodiments, the polymer portion is an oligosiloxane or polysiloxane, particularly a poly(di-C1~C4-alkyl)siloxane. In some embodiments, the poly(di-C1~C4-alkyl)siloxane may have 20 to 200 repeating units. In some embodiments, the poly(di-C1~C4-alkyl)siloxane is polydimethylsiloxane (dimethicone). 【0174】 In some embodiments, the polymer portion is a polyether, particularly a polyether containing ethylene oxide repeating units, propylene oxide repeating units, or mixtures thereof. Examples include polyethylene glycol (PEG) and polypropylene glycol (PPG). 【0175】 In some embodiments, the polymer portion is a polyamine, or a polymer containing a polyamine such as PEG-15 taluamine. 【0176】 In some embodiments, the polymer portion is polyquaternium, particularly polyquaternium-16, polyquaternium-46, polyquaternium-11, polyquaternium-28, polyquaternium-6, polyquaternium-7, polyquaternium-22, polyquaternium-39, polyquaternium-2, polyquaternium-17, or polyquaternium-18. 【0177】 In some embodiments, C1~C 60 The portion may have a molecular weight of 140 g / mol to 2000 g / mol, more specifically 160 g / mol to 1600 g / mol, and particularly 180 g / mol to 1200 g / mol. 【0178】 In some embodiments, C1~C 60 The portion may have 31 or more carbon atoms. 【0179】 In some embodiments, C1~C 60 The portion is saturated or unsaturated C. 10 ~C 60 The aliphatic portion, more specifically C 15 ~C 60 aliphatic portion, especially C 20 ~C 60 It may include aliphatic parts. 【0180】 In some embodiments, C1~C 60 The ratio of heteroatoms in the part to the total heteroatoms may be approximately 60:1 to 5:1, more specifically approximately 50:1 to 10:1, and especially approximately 40:1 to 20:1, and the heteroatoms are selected from nitrogen and oxygen. 【0181】 In some embodiments, C1~C 60 This may be fatty acids, fatty alcohols or their derivatives, more specifically saturated or unsaturated fatty acids, fatty alcohols or their derivatives, particularly caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, linoleic acid, decyl alcohol, dodecyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, or fatty acid mono-, di-, or triglycerides, particularly caprylic acid glyceride, capric acid glyceride, or stearate glyceryl. 【0182】 In some embodiments, C1~C 60 The portion may be sphingosine or its derivatives, particularly ceramide or sphingomyelin. 【0183】 In some embodiments, b) C1-C 60 The portion or polymer portion may be configured to act as a skin moisturizer. 【0184】 In some embodiments, b) C1-C60 The portion or polymer portion may be configured to act as a skin moisturizer after cleavage from the 3,4-dihydro-2H-pyran portion. 【0185】 b) C1~C 60 In some embodiments in which a portion or polymer portion is configured to act as a skin moisturizer and / or to act as a skin moisturizer after cleavage from the 3,4-dihydro-2H-pyran portion, it may be particularly advantageous that the compound of formula (I) is one of the compounds of formulas (II), (III), (IV), or (V) defined above. 1 It can also be particularly advantageous that represents H. 【0186】 Compounds that act as insecticides In some embodiments, at least one of A1, A2, and A3 is configured to act as an insecticide and / or to act as an insecticide after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C 60 Partial is also acceptable. 【0187】 In some embodiments, the insecticide may be an insecticide. For the purposes of this disclosure, an insecticide is a chemical used to incapacitate insects without killing or rendering them incapacitated, in particular by making the host (i.e., the object to which the insecticide is applied) less attractive to insects. 【0188】 In some embodiments, the insecticide may be an insecticide. For the purposes of this disclosure, an insecticide is a chemical substance used to control insects by killing or incapacitating them. 【0189】 In some embodiments, insecticides or insecticides may act against ectoparasites and / or blood-sucking insects, particularly blood-sucking insects selected from the group consisting of mosquitoes, ticks, mites, gnats, fleas, chiggers, leeches, and other insects. Ectoparasites are organisms that live on the skin of a host and obtain their nutrients from the skin. 【0190】 In some embodiments, the insecticide may be an insecticide that can be selected from isoprenoids, tertiary amides, and phenylpropanoids. 【0191】 In some embodiments, the insecticide may be an isoprenoid, more specifically a monoterpenoid, diterpenoid, or triterpenoid, in particular terpineol or its derivatives, monoterpenoid aldehyde or its derivatives, limonoid or its derivatives; or pyrethrin or its derivatives. In some embodiments, the isoprenoid may be selected from citronellal, hydroxycitronellal, citronellol, citral A, citral B, or their derivatives; necrodan, in particular α-necrodol, or its derivatives; limonoid, in particular azathilactin, or its derivatives; or pyrethrin, in particular jasmolin, synerin, or their derivatives. 【0192】 In some embodiments, the insecticide may include a tertiary amide. In some embodiments, the tertiary amide may be selected from picaridin, N,N-di(C1-C6-alkyl)-toluamide, particularly N,N-diethyl-meth-toluamide, ethyl 3-(N-butylacetamide)propanoate, and derivatives thereof. 【0193】 In some embodiments, the insect repellent may be selected from one of the following compounds and their part / derivatives: N,N-diethyl-meth-toluamide, diethylphenylacetamide, N-butylacetanilide, ethyl butylacetylaminopropionate, picaridin, N-(2-methylpiperidine-1-yl)cyclohexa-3-ene-1-carboxyamide, and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine or 1-[3-cyclohexen-1-ylcarbonyl]piperidine. 【0194】 In some embodiments, the insecticide may be a phenylpropanoid, particularly eugenol or a derivative thereof. 【0195】 In some embodiments, at least one of A1, A2, or A3 may be selected from the part of formula (VIa) or formula (VIb). 【0196】 [ka] 【0197】 b) C1~C 60 In some embodiments in which a portion or polymer portion is configured to act as an insecticide and / or to act as an insecticide after cleavage from the 3,4-dihydro-2H-pyran portion, it may be particularly advantageous that the compound of formula (I) is one of the compounds of formulas (II), (III), (IV), or (V) defined above. 1 It can also be particularly advantageous that represents H. 【0198】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (VII), 【0199】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L5 either does not exist, or is -C(O)-, -C(O)-O-, -C(O)-O-(CH2). 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, -S(O)2-, -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - may be any of the following: R 4 This may be selected from H or C1-C4 alkyl groups. 【0200】 In some embodiments, R 3 C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0201】 In some embodiments, R 1 It may be particularly advantageous that represents H. In some embodiments, it may be even more particularly advantageous that L5 exists and is selected from -C(O)-, -C(O)-O-, -C(O)-NHC(O)-, or -C(O)-NHC(O)-O-. 【0202】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (VIII), 【0203】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally chosen substituent. 【0204】 In some embodiments, R 3 C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0205】 In some embodiments, R 3 R may represent H or methyl, 1 This can also represent H. 【0206】 In some embodiments, the compounds of the present invention are derived from picaridin, in particular. 【0207】 In some embodiments, one of A1, A2, or A3 may be part of formula (IX). 【0208】 [ka] 【0209】 In some embodiments, one of A1, A2, or A3 may be part of formula (X). 【0210】 [ka] 【0211】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (XI), 【0212】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L6 is either non-existent or -(CH2) 1~4 , -C(O)-, -C(O)-O-, -C(O)-O-(CH2) 1~4 -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, -S(O)2-, -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - or a group selected from a combination thereof R 4 This may be selected from H or C1-C4 alkyl groups. 【0213】 In some embodiments, R 3 It may be particularly advantageous to include 1 to 14 atoms, more specifically 1 to 12, especially 1 to 8 carbon atoms; 0 to 12 atoms, more specifically 0 to 8, especially 0 to 6 oxygen atoms; 0 to 8 atoms, more specifically 0 to 6, especially 0 to 4 nitrogen atoms; 0 to 6 atoms, more specifically 0 to 4, especially 0 to 3 sulfur atoms; and 0 to 10 atoms, more specifically 0 to 8, especially 0 to 6 halogen atoms. 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0214】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (XII), 【0215】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally chosen substituent. 【0216】 In some embodiments, R 3 C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0217】 In some embodiments, R 3 R may represent H or methyl, 1 This can also represent H. 【0218】 In some embodiments, the insecticide may be an insecticide selected from or derived from insecticides, particularly permethrin; cypermethrin; deltamethrin; ivermectin; amidine, particularly amitraz; benziocarb; malathion; carbaryl; diazinon; dichlorodiphenyltrichloroethane (DDT); fenthion; fipronil; imidacloprid; nitenpyram; and propoxur. 【0219】 In some embodiments, C1~C 60 The portion may be configured to act as an insecticide, particularly as an insect repellent. 【0220】 In some embodiments, C1~C 60 The portion may be composed of an insecticide, particularly an insect repellent, after being cleaved from the 3,4-dihydro-2H-pyran portion. 【0221】 Compounds that act as skin whitening agents In some embodiments, at least one of A1, A2, and A3 is configured to act as a skin whitening agent and / or to act as a skin whitening agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 It may be a part or a polymer part. 【0222】 In some embodiments, the skin whitening agent may act by chemically or metabolically whitening the skin, particularly by providing a fading effect or reducing melanin production. 【0223】 In some embodiments, the skin whitening agent may be selected from corticosteroids, particularly clobetasol derivatives, fluocinolone derivatives, or betamethasone; vitamin A derivatives, particularly tretinoin, isotretinoin, alitretinoin, retinol, or retinal; hydroxyphenol derivatives, particularly hydroquinone; aliphatic dicarboxylic acids, particularly acelaic acid; α-hydroxy acids, particularly lactic acid and glycolic acid; and vitamin C and its derivatives. 【0224】 In some embodiments, b) C1-C 60 The portion or polymer portion may be configured to act as a skin whitening agent. 【0225】 In some embodiments, b) C1-C 60 The partial or polymer portion may be configured as a skin whitening agent after cleavage from the 3,4-dihydro-2H-pyran portion. 【0226】 b) C1~C 60 In some embodiments in which a portion or polymer portion is configured to act as a skin whitening agent and / or to act as a skin whitening agent after cleavage from the 3,4-dihydro-2H-pyran portion, it may be particularly advantageous that the compound of formula (I) is one of the compounds of formulas (II), (III), (IV), or (V) defined above. 1It can also be particularly advantageous that represents H. 【0227】 Compounds that act as fragrances In some embodiments, at least one of A1, A2, and A3 is configured to act as an air freshener after cleavage from the 3,4-dihydro-2H-pyran moiety of group C1-C 60 Partial is also acceptable. 【0228】 In some embodiments, C1~C 60 The section is C1~C 60 The portion may contain a functional group that bonds to the corresponding L1, L2, or L3 portion, or, if the corresponding L1, L2, or L3 portion is absent, to the 3,4-dihydro-2H-pyran portion. In some embodiments, the functional group is configured to be cleaved into an aldehyde, ketone, thiol, hydroxyl, or amine. 【0229】 In some embodiments, the functional group may be an imine, acetal, 1,1-diester, enol ether, ester, amide, thioester, or thioacetal. 【0230】 In some embodiments, C1~C 60 The portion may have a molecular weight after cleavage of less than 400 g / mol, more specifically less than 300 g / mol, and particularly less than 200 g / mol. 【0231】 In some embodiments, the fragrance is selected from the group consisting of esters, aldehydes, ketones, thiols, lactones, alcohols, linear terpenes, cyclic terpenes, aromatics, and amines. 【0232】 In some embodiments, the fragrance is not benzyl alcohol or hexanol. 【0233】 b) C1~C 60In some embodiments in which the portion is configured to act as an aromatherapy agent after cleavage from the 3,4-dihydro-2H-pyran moiety, it may be particularly advantageous that the compound of formula (I) is one of the compounds of formulas (II), (III), (IV), or (V) defined above. 1 It can also be particularly advantageous that represents H. 【0234】 Compounds that act as pharmaceuticals In some embodiments, at least one of A1, A2, and A3 is configured to act as a pharmaceutical agent and / or to act as a pharmaceutical agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 It may be a part or a polymer part. 【0235】 In some embodiments, the pharmaceutical product may be suitable for treating skin-related diseases. In some embodiments, skin-related conditions may be selected from acneiform rash, autoinflammatory syndrome, chronic blistering, mucosal membrane conditions, skin appendage conditions, subcutaneous fat conditions, congenital anomalies, connective tissue disorders, fibrous and elastic tissue abnormalities, skin growth and subcutaneous growth, dermatitis, eczema, seborrheic dermatitis, pigment disorders, endocrine-related skin conditions, eosinophilic skin conditions, skin lesions, skin cancer, erythema, hereditary dermatology, infection-related skin conditions, lichenoid rash, lymphatic system-related skin conditions, melanocyte nevi and neoplasms, monocyte-related and macrophage-related skin conditions, mucinosis, neurocutaneous conditions, non-infectious immunodeficiency-related skin conditions, nutrition-related skin conditions, papular desquamation keratosis, palmoplantar keratoderma, pruritus, psoriasis, reactive neutrophilic skin conditions, skin conditions due to metabolic disorders, skin conditions due to physical factors, urticaria, dandruff, desquamation disorders, and vascular-related skin conditions. 【0236】 In some embodiments, the pharmaceutical product may be suitable for treating an allergic condition. In some embodiments, the pharmaceutical product may be an antihistamine. 【0237】 In some embodiments, the pharmaceutical(s) may not be a compound(s) for the prevention of sunburn, skin cancer, and / or other skin conditions associated with UV-A / UV-B exposure. 【0238】 In some embodiments, at least one of A1 and A2 is configured to act as a pharmaceutical agent and / or to act as a pharmaceutical agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 It may be a part or a polymer part. 【0239】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (XIII), 【0240】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L7 is -C(O)-, -C(O)-(CH2) 1~4 -, -C(O)-O-, -C(O)-O-(CH2) 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, or -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - is a group selected from R 4 This is selected from H or C1-C4 alkyl. 【0241】 In some embodiments, R 3C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0242】 In some embodiments, R 3 R may represent H or methyl, 1 This can also represent H. 【0243】 In some embodiments, L7 is -C(O)-, -C(O)-O-(CH2) 1~4 -, or -C(O)-NHC(O)-C(O)-O-(CH2) 1~4 - Choosing from this option may be even more particularly advantageous. 【0244】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (XIV), 【0245】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally chosen substituent. 【0246】 In some embodiments, R 3 It may be particularly advantageous to include 1 to 14 atoms, more specifically 1 to 12, especially 1 to 8 carbon atoms; 0 to 12 atoms, more specifically 0 to 8, especially 0 to 6 oxygen atoms; 0 to 8 atoms, more specifically 0 to 6, especially 0 to 4 nitrogen atoms; 0 to 6 atoms, more specifically 0 to 4, especially 0 to 3 sulfur atoms; and 0 to 10 atoms, more specifically 0 to 8, especially 0 to 6 halogen atoms. 3 C 1~14Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4 Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0247】 In some embodiments, R 3 R may represent H or methyl, 1This can also represent H. 【0248】 In some embodiments, the pharmaceutical product may be suitable for treating alopecia. 【0249】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (XV), 【0250】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R 5 This represents H, OH, C1-C4-alkyl, NH2, N(C1-C4-alkyl)2, N-morpholino-1-yl, or piperidine-1-yl. L8 is -C(O)-, -C(O)-(CH2) 1~4 -, -C(O)-O-, -C(O)-O-(CH2) 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, or -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - is a group selected from R 4 This is selected from H or C1-C4 alkyl. 【0251】 In some embodiments, R 3 R may represent H or methyl, 1 This can also represent H. 【0252】 In some embodiments, R 3C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0253】 In some embodiments, L8 is -C(O)-, -C(O)-O-(CH2) 1~4 -, or -C(O)-NHC(O)-C(O)-O-(CH2) 1~4 - Choosing from this option may be even more particularly advantageous. 【0254】 In some embodiments, R 5 may represent H (i.e., copexyl) or piperidine-1-yl (i.e., minoxidil). 【0255】 In some embodiments, the compound that can covalently bond to the skin is the compound of formula (XVI), 【0256】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R 5 This represents H, OH, C1-C4-alkyl, NH2, N(C1-C4-alkyl)2, N-morpholino-1-yl, or piperidine-1-yl. 【0257】 In some embodiments, R 3C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 Represents a part. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 It may be particularly advantageous for further substitutions to be made at will, provided that the sum of the elements listed above does not exceed the aforementioned total. 3 It may also be advantageous for R to represent a optionally substituted phenyl. 3 R represents an optionally substituted phenyl, and it may be particularly advantageous that the optionally substituted phenyl comprises 6 to 14, more specifically 6 to 12, particularly 6 to 10 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. In some of these embodiments, R 3 is -C 1~4 Alkyl, -OC 1~4 Alkyl, -SC 1~4 Alkyl, -NH-C 1~4 Alkyl, -N(C 1~4 Alkyl)2,-C(O)C 1~4 Alkyl, -CO2C 1~4 Alkyl, -O2C-C 1~4 Alkyl, -C(O)NH-C 1~4 Alkyl, -C(O)N(C 1~4 Alkyl)2,-NH-C(O)C 1~4 Alkyl, -N(C 1~4Alkyl)-C(O)C 1~4 It is substituted with one or more moieties selected from the group consisting of alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogens, especially Cl, Br or F, and -CF3. 【0258】 In some embodiments, R 3 R may represent H or methyl, 1 This can also represent H. 【0259】 In some embodiments, R 5 may represent H (i.e., copexyl) or piperidine-1-yl (i.e., minoxidil). 【0260】 In some embodiments, the pharmaceutical may be suitable for treating pain or inflammation. In some embodiments, the pharmaceutical may be an analgesic or a corticosteroid. In some embodiments, the analgesic is acetaminophen (INN-paracetamol). In some embodiments, the analgesic is acetaminophen bonded to the rest of the compound via its hydroxyl group. 【0261】 In some embodiments, the pharmaceutical may be suitable for inducing a hot or cold skin sensation. In some embodiments, the pharmaceutical formulation may be menthol, camphor; or a derivative thereof. In some embodiments, the pharmaceutical formulation may be an alkaloid, more specifically a capsaicinoid, in particular capsaicin, or a derivative thereof. 【0262】 In some embodiments, the pharmaceutical formulation may be selected from nicotinamide and its derivatives or undecylenic acid and its derivatives. 【0263】 In some embodiments, C1~C 60 The portion may be an agonist of a retinoid receptor, more specifically a retinoic acid receptor, a retinoid X receptor, and / or a RAR-related orphan receptor. 【0264】 In some embodiments, C1~C 60 The portion may include vitamin A vitamers, more specifically retinol, tretinoin, isotretinoin, ali-tretinoin, etretinate, acitretin, adapalene and / or bexarotene, particularly vitamers selected from the group of retinol, retinal and / or adapalene. 【0265】 In some embodiments, b) C1-C 60 The portion or polymer portion may be configured to act as a dermatological drug. 【0266】 In some embodiments, b) C1-C 60 The portion or polymer portion may be configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran portion. 【0267】 In some embodiments, b) C1-C 60 The portion may not contain salicylic acid and its derivatives, nor may it be derived from salicylic acid and its derivatives. In some embodiments, the compound and / or topical composition according to formula (I) does not contain an ester of salicylic acid. This includes both esters formed with the hydroxyl group of salicylic acid and esters formed with the carboxylic acid of salicylic acid. 【0268】 In some embodiments, at least one of A1, A2, and A3 is configured to act as a pharmaceutical agent and / or to act as a pharmaceutical agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 It may be a part or a polymer part. 【0269】 In some embodiments, at least one of A1 and A2 is configured to act as a pharmaceutical agent and / or to act as a pharmaceutical agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60It may be a part or a polymer part. In some embodiments, at least one of A1 and A2 is configured to act as a pharmaceutical and / or to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 A3 may be a part or a polymer part, and A3 may be a part of group a). In some embodiments, A1 is configured to act as a pharmaceutical and / or to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran part, C1-C of group b). 60 They may be parts or polymer parts, and A2 and A3 may be parts of group a). 【0270】 In some embodiments, b) C1-C 60 The portion and / or polymer portion is not a coloring portion, in particular, not a coloring portion having at least one absorption peak in the wavelength range of 380 to 790 nm. 【0271】 In some embodiments, b) C1-C 60 The portion and / or polymer portion is not a UV-absorbing portion, in particular not a UVA-absorbing portion and / or a UVB-absorbing portion, in particular not a UVA-absorbing portion and / or a UVB-absorbing portion having at least one absorbent peak in the wavelength range of 280 to 379 nm. 【0272】 In some embodiments, any of the compounds of formulas (I) to (V) are not compounds disclosed in International Publication No. 2023 / 102652(A1), the contents of which are incorporated herein by reference for this purpose. Specifically, in some embodiments, any of the compounds of formulas (I) to (V) are R in formula (IX) of International Publication No. 2023 / 102652(A1). 3 It is not a compound containing portions A1, A2 and / or A3. 【0273】 In some embodiments, any of the compounds of formulas (I) to (V) are not compounds disclosed in International Publication No. 2014 / 155016(A1), in particular, R''1, R''2 and R''4 are as defined in the table below the formula, and R''3 is C 12 H 25 It is not a compound disclosed in formula (II) representing S-. The contents of International Publication No. 2014 / 155016(A1) are incorporated herein by reference for this purpose. 【0274】 In some embodiments, the C1-C1 group is configured to act as an aromatherapy agent after cleavage from the 3,4-dihydro-2H-pyran moiety. 60 In the case of A3 representing a part or polymer part, A3 does not represent a benzyloxy part or an alkoxy part, in particular a hexyloxy part. 【0275】 In some embodiments, the compounds of formula (I) and formula (II) are not compounds in which L1-A1 represents a portion containing a hydroxyl group bonded to the carbon atom in the alpha position relative to the carbon atom marked "a" in formula (I). 【0276】 In some embodiments, any of the compounds of formulas (I) to (V) are not compounds disclosed in U.S. Patent No. 6,022,888, which is incorporated herein by reference for this purpose. 【0277】 In some embodiments, the compounds of the present disclosure do not contain epoxy groups. 【0278】 While certain embodiments of this disclosure have often been discussed in relation to hydrogenated genipine derivatives, it should be understood that this disclosure is not limited to these derivatives. Rather, many alternative 3,4-dihydro-2H-pyran derivatives are available to those skilled in the art, equally suitable for and included in this disclosure. Alternative examples based on hydrogenated versions of deglycosylated oleuropein are described below. 【0279】 Therefore, in some embodiments, the compound of formula (I) that can be covalently bonded to the skin is the compound of formula (XVII), 【0280】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 , L1, L3, A 1, A2 and A3 are as defined in any prior embodiment, and L1 is selected from the group consisting of -CH2-, -C(O)-, C(O)-O-, -C(O)-NH-, -C(O)-N(C1~C4-alkyl)-, and combinations thereof. 【0281】 formulation Topical compositions include, but are not limited to, any such compositions for topical administration. Topical administration as understood in this disclosure means any topical (i.e., not systemic) administration of the compounds or compositions of this disclosure, whether via ointments, gels, creams, lotions, or other similar formulations, and includes direct administration to the external epidermis or dermis of a subject, including administration to skin appendages such as hair, but not oral, rectal, intrapulmonary, or intranasal administration. 【0282】 As one form of topical composition, the Disclosure further relates, in some embodiments, to compounds or compositions of the Disclosure for use as cosmetic. In this application, cosmetic or aesthetic use means that the composition is suitable for external use (i.e., extracorporeal use, e.g., non-ingestion), and in particular suitable for application to the skin or hair. 【0283】 In general, the compositions described above can be formulated in any form known in the art for cosmetic (topical) administration. Therefore, the compositions can be applied in any topical form, such as aerosol sprays, creams, emulsions, solids, liquids, dispersions, foams, oils, gels, hydrogels, lotions, mousses, ointments, powders, patches, pomades, solutions, pump sprays, sticks, towels, soaps, or other forms commonly used in the field of topical administration and / or cosmetic / sunscreen and skincare formulations. The compositions may also be water-resistant (e.g., waterproof). 【0284】 Topical compositions may also exist in the form of patches or carriers containing the topical composition. Examples of patches include adhesive labels or thin foils coated or printed with the composition. Examples of carriers include nonwoven materials or hydrogels impregnated with the composition. 【0285】 The compositions of this disclosure may contain any one of the compounds described herein in an amount ranging from 0.005% to 99% by weight, with the remainder consisting of a suitable excipient. The compositions to be considered may contain any one of the compounds provided herein in an amount ranging from 0.01% to 99% by weight, 0.1 to 95% by weight in one embodiment, 75 to 85% by weight in another embodiment, and 20 to 80% by weight in a further embodiment, with the remainder consisting of any excipient described herein, or any combination thereof. 【0286】 The topical compositions according to this disclosure further comprise excipients suitable for topical administration. The excipients are not particularly limited. In some embodiments, the excipients suitable for topical administration comprise one or more excipients selected from water, ethanol, isopropanol, n-propanol, ethylene glycol, diethylene glycol, propylene glycol, diethylene glycol monoethyl ether, DMSO, and glycerol. 【0287】 In some embodiments, topical compositions may also be pre-dispersed compositions comprising the compounds and liquid carriers of the Disclosure. These compositions may be solutions (e.g., free from any undissolved solid particles), dispersions (e.g., containing a liquid phase and a solid precipitating agent phase), or emulsions. 【0288】 In some embodiments, the topical composition may contain water and / or an organic solvent as a suitable carrier and excipient. In one example, the liquid composition may be sterile and / or prepared from a sterile aqueous solution for injection. 【0289】 In some embodiments, the composition may also contain surfactants such as alkylbenzene sulfonates, alkyl sulfates, alkyl ether sulfates, soaps, ethoxylates, alkyl alcohols, lignosulfonates, or triglycerides. The composition may also contain a solid matrix. Suitable examples of matrix components include sugars, sugar alcohols (e.g., sorbitol, mannitol, xylitol, isomalt, hydrolyzed starch hydrolysates), polymers, or combinations of two or more thereof. 【0290】 In some embodiments, the composition may also contain a skin penetration enhancer. As used herein, “skin penetration enhancer” refers to a substance (penetrator) that penetrates the skin and reversibly reduces barrier resistance. In some embodiments, the skin penetration enhancer can also increase the load by promoting the solubility of the penetrator, which can, for example, promote the flux of the penetrator across the skin. Non-limiting examples of skin penetration enhancers include alcohols, amides, esters, ether alcohols, fatty acids, glycols, pyrrolidones, sulfoxides, surfactants, and terpenes. 【0291】 In some embodiments, the composition may also contain preservatives, thickeners, film-forming agents and / or wetting agents. Non-limiting examples of thickeners include starch, gum (e.g., natural and synthetic gum), cellulose, and arabinogalactan. Non-limiting examples of wetting agents include polyhydric alcohols, e.g., polyalkylene glycols (e.g., alkylene polyols and their derivatives), alpha hydroxy acids, sugars, aloe vera gel, vegetable oils, lithium chloride, allantoin, urea, and dicyanamide. Non-limiting examples of film-forming agents include volatile silicone resins, polyvinylpyrrolidone, acrylates, acrylamides, copolymers, and isododecane resins. 【0292】 The composition can be applied to the target skin using inkjet printing directly onto a skin transfer substrate such as a patch. In this case, the composition is applied to the transfer substrate using a printer nozzle. In some embodiments, the composition may also be contained in a pen-like applicator, as this may allow for more selective local delivery. 【0293】 In some embodiments, topical formulations containing the compound of formula (I) are storage stable for more than one month, more specifically more than three months, and especially more than six months, when stored at 21°C and 25% RH (i.e., the compound of formula (I) retains its original chemical structure in greater than 95 mol%). In some embodiments, the water solubility of the compound of formula (I) is about 1 g / L to about 100 g / L, about 5 g / L to about 50 g / L, or about 10 g / L to about 100 g / L. 【0294】 In some embodiments, it may be particularly advantageous that the topical composition is not too "flowy" in order to facilitate local retention of the topical formulation on the skin at the administration site. Therefore, it may be particularly advantageous that the topical composition has a dynamic viscosity, measured at 37°C, greater than 2 mPa·s, more specifically greater than 10 mPa·s, and especially greater than 50 mPa·s, for example, in the range of 2 mPa·s to 50,000 mPa·s, more specifically in the range of 10 mPa·s to 20,000 mPa·s, and especially in the range of 50 mPa·s to 10,000 mPa·s. Suitable measurement methods are well known in the art and include ASTM D-2196-20 using test method A at 30 rpm, or DIN EN ISO 2555:2018-09 at 30 rpm, using a rotational viscometer, for example, the ViscoQC 100, available from Anton Paar GmbH (Germany), optionally equipped with a PTD 100 cone plate for smaller sample sizes. 【0295】 In some embodiments, the hair care formulation is enclosed in a container. In some embodiments, the container is sealed and / or dispensed after opening. In some embodiments, the container includes a label and / or packaging is provided. 【0296】 Further uses and methods In a second aspect, the present disclosure relates to a compound of formula (I), 【0297】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. This relates to compounds of formula (I), or their tautomers and / or pharmaceutically acceptable salts, for use in medicine. 【0298】 Any of the specific compounds disclosed in the first aspect of this disclosure, which pertain to the pharmaceutical portion, also represent specific embodiments of this aspect of the disclosure. 【0299】 In a third aspect, the present disclosure relates to a compound of formula (I), 【0300】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. The present invention relates to a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, for use in the treatment of skin-related diseases, allergic conditions, pain, or inflammation. 【0301】 In some embodiments, skin-related conditions may be selected from acneiform rash, autoinflammatory syndrome, chronic blister formation, mucosal conditions, skin appendage conditions, subcutaneous fat conditions, congenital anomalies, connective tissue disorders, abnormalities of skin fibers and elastic tissue, skin growth and subcutaneous growth, dermatitis, eczema, seborrheic dermatitis, pigment disorders, endocrine-related skin conditions, eosinophilic skin conditions, skin lesions, skin cancer, erythema, hereditary dermatology, infection-related skin conditions, lichenoid rash, lymphatic system-related skin conditions, melanocyte nevi and neoplasms, monocyte-related and macrophage-related skin conditions, mucinosis, neurocutaneous conditions, non-infectious immunodeficiency-related skin conditions, nutrition-related skin conditions, papular desquamation keratosis, palmoplantar keratoderma, pruritus, psoriasis, reactive neutrophilic skin conditions, skin conditions due to metabolic disorders, skin conditions due to physical factors, urticaria, dandruff, desquamation disorders, and vascular-related skin conditions. 【0302】 In some embodiments, the skin-related disorder is selected from alopecia, psoriasis, desquamation disorder, and seborrheic dermatitis. 【0303】 Any of the specific compounds disclosed in the first aspect of this disclosure, which pertain to the pharmaceutical portion, also represent specific embodiments of this aspect of the disclosure. 【0304】 In a fourth aspect, the present disclosure relates to a compound of formula (I), 【0305】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety C1-C 60 It is a part or a polymer part, L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. For medical use, particularly in skin-related disorders, allergic conditions, pain, or inflammation, the pharmaceutical product relates to a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, which are released over a period of hours or days. 【0306】 In some embodiments, the multiple hours are 8 hours or more, more specifically 12 hours or more, and especially 24 hours or more. 【0307】 In some embodiments, multiple days means two or more days, more specifically three or more days, and especially seven or more days. 【0308】 Any of the specific compounds disclosed in the first aspect of this disclosure, which pertain to the pharmaceutical portion, also represent specific embodiments of this aspect of the disclosure. 【0309】 In a fifth aspect, the disclosure relates to the use of the topical composition according to the first aspect as a skin moisturizer, insecticide, particularly insect repellent, skin whitening agent, or fragrance agent. 【0310】 Any particular compound disclosed in the first aspect of this disclosure, which targets one (or more) parts used as a skin moisturizer, insecticide, particularly insect repellent, skin whitening agent, or fragrance agent, also represents a particular embodiment of this aspect of the disclosure. 【0311】 In a sixth aspect, the disclosure relates to a method of using a topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound that can covalently bond to the skin is a compound of formula (I), 【0312】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Consistently configured to act as a skin moisturizer, insecticide, or skin whitening agent, and / or b2) After cleavage from the 3,4-dihydro-2H-pyran moiety, it is configured to act as a skin moisturizer, insecticide, skin whitening agent, or fragrance. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. The method relates to a method that includes applying a topical composition to the skin. 【0313】 In some embodiments, the method may include leaving the topical composition on the skin for at least 30 minutes. 【0314】 In some embodiments, the method may include chemically exfoliating the skin before applying the topical composition to the skin. 【0315】 Any of the specific compounds that are part of portion a disclosed in the first aspect of this disclosure and used as a skin moisturizer, insecticide, skin whitening agent, or fragrance also represent specific embodiments of this aspect of the disclosure. 【0316】 In a seventh aspect, the Disclosure relates to a method for treating a domesticated animal or livestock, the method comprising applying a topical composition to the skin and / or coat of the domesticated animal or livestock, the topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, the compound that can covalently bond to the skin being a compound of formula (I), 【0317】 [ka] or its tautomers and / or pharmaceutically acceptable salts, in which, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as an insecticide and / or b2) It is configured to act as an insecticide after cleavage from the 3,4-dihydro-2H-pyran moiety. The method relates to a method in which L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. 【0318】 Any particular compound disclosed in the first aspect of this disclosure, which targets one (or more) parts used as an insecticide, also represents a particular embodiment of this aspect of the disclosure. 【0319】 In the eighth aspect, the disclosure is specifically independent of the compounds of the disclosure themselves, i.e., the topical compositions. 【0320】 Any of the compounds disclosed in the first aspect of this disclosure also represent a specific embodiment of this aspect of the disclosure. 【0321】 definition As used herein, the term “hair” refers to hair, as well as other fibrous keratinous substances such as eyebrows and eyelashes. 【0322】 As used herein, the term “about” means “approximately” (for example, plus or minus approximately 10% of the indicated value). For example, “about 20” means a quantity including or including 18 to 22 and 22. 【0323】 In various parts of this specification, substituents of the compounds of the present invention are disclosed in groups or ranges. The present invention is specifically intended to include all individual subcombinations of members of such groups and ranges. For example, "C 1~6 The term "alkyl" is specifically intended to disclose methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl individually. 【0324】 As used herein, the term "carboxy" refers to the -C(O)OH group. 【0325】 Throughout the definition, "C n~m The term "range" indicates a range including the endpoints, where n and m are integers representing the number of carbon atoms. For example, C 1~4 , C 1~6 These are some examples. 【0326】 As used herein, "C" is used alone or in combination with other terms. n~m The term "alkyl" refers to a saturated hydrocarbon group having n to m carbon atoms, which may be linear or branched. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, and sec-butyl; and higher homologs, such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, and 1,2,2-trimethylpropyl, but are not limited to these. In some embodiments, the alkyl group contains 1 to 6 carbon atoms, more specifically 1 to 4 carbon atoms, even more specifically 1 to 3 carbon atoms, and especially 1 to 2 carbon atoms. 【0327】 As used herein, "C" is used alone or in combination with other terms. n~mThe term "acyl" refers to a saturated hydrocarbon group that has n to m carbon atoms and can be linear or branched. 【0328】 As used herein, "C" is used alone or in combination with other terms. n~m The term "haloalkyl" refers to an alkyl group having one halogen atom ~2s+1 halogen atoms, which may be the same or different, where "s" is the number of carbon atoms in the alkyl group, and the alkyl group has n ~ m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group has 1 ~ 6, 1 ~ 4, or 1 ~ 3 carbon atoms. 【0329】 When used herein, "C n~m An "alkenyl" refers to an alkyl group having one or more carbon-carbon double bonds and containing n to m carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, and sec-butenyl. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. 【0330】 When used herein, "C n~m "Alkynyl" refers to an alkyl group having one or more carbon-carbon triple bonds and containing n to m carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl, propyne-1-yl, and propyne-2-yl. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. 【0331】 As used herein, "C" is used alone or in combination with other terms. n~mThe term "alkylene" refers to a divalent alkyl linking group having n to m carbon atoms. Examples of alkylene groups, but not limited to these, include ethane-1,1-diyl, ethane-1,2-diyl, propane-1,1-diyl, propane-1,3-diyl, propane-1,2-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl, and 2-methylpropane-1,3-diyl. In some embodiments, the alkylene portion contains 2 to 6, 2 to 4, 2 to 3, 1 to 6, 1 to 4, or 1 to 2 carbon atoms. 【0332】 As used herein, the term "amino" refers to the group of formula -NH2. 【0333】 As used herein, the term “fat” in fatty acids or fatty alcohols refers to a linear or branched saturated, monounsaturated, or polyunsaturated hydrocarbon portion having 8 to 34 carbon atoms. Examples of fatty acids include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid; linolenic acid, arachidonic acid, oleic acid, and meadic acid. Examples of fatty alcohols include decanol, undecanol, cetyl alcohol, stearyl alcohol, oleyl alcohol, myricyl alcohol, and gezyl alcohol. 【0334】 As used herein, the term "halogen" refers in particular to F, Cl, Br, and I. 【0335】 As used herein, the term “compound” includes all stereoisomers, geometric isomers, tautomers, and isotopes of the structure shown. A compound identified herein by name or structure as a specific tautomer is intended to include other tautomers unless otherwise specified. 【0336】 The compounds described herein may be asymmetric (e.g., having one or more stereocenters). All stereoisomers (e.g., enantiomers and diastereomers) are intended unless otherwise indicated. Compounds of the present invention containing asymmetrically substituted carbon atoms can be isolated as optically active or racemic forms. Methods for preparing optically active forms from optically inert starting materials are known in the art, for example, by the resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers, such as olefins, C=N double bonds, and N=N double bonds, can also be present in the compounds described herein, and all such stable isomers are intended in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and can be isolated as mixtures of isomers or as separated isomeric forms. In some embodiments, the compounds have an (R)-configuration. In some embodiments, the compounds have an (S)-configuration. 【0337】 The compounds provided herein also include tautomers. Tautomers arise from the exchange of a single bond with an adjacent double bond along with the simultaneous transfer of a proton. Tautomers include prototropic tautomers, which are isomeric protonated states having the same empirical formula and total charge. Examples of prototropic tautomers include ketone-enol pairs, amide-imoid acid pairs, lactam-lactim pairs, enamine-imine pairs, and cyclic forms in which protons can occupy two or more positions in a heterocyclic system, such as 1H- and 3H-imidazoles, 1H-, 2H- and 4H-1,2,4-triazoles, 1H- and 2H-isoindoles, and 1H- and 2H-pyrazoles. Tautomers may exist in equilibrium or may be sterically fixed into one form by appropriate substitution. 【0338】 When used herein, a “salt” or “pharmaceutically acceptable salt” of any one of the compounds of the formulas disclosed herein is formed between an acidic group and a basic group of the compound, such as an amino functional group, or between a basic group and an acidic group of the compound, such as a carboxyl functional group. According to another embodiment, the compound is a pharmaceutically acceptable acid addition salt. In some embodiments, acids commonly used to form a pharmaceutically acceptable salt of any one of the compounds of the formulas include inorganic acids such as hydrogen sulfide, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid and phosphoric acid, as well as organic acids such as p-toluenesulfonic acid, salicylic acid, tartaric acid, bitartaric acid, ascorbic acid, maleic acid, besylic acid, fumaric acid, gluconic acid, glucuronic acid, formic acid, glutamic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, lactic acid, oxalic acid, p-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid and acetic acid, as well as related inorganic and organic acids. Therefore, these pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caprinates, heptanoates, propioates, oxalates, malons, succinates, suberates, sebacinates, fumarates, maleates, butin-1,4-dioate, hexin-1,6- Examples of salts include dioates, benzoates, chlorobenzoates, methyl benzoate, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, terephthalates, sulfonates, xylene sulfonates, phenyl acetates, phenylpropionates, phenyl butyrates, citrates, lactates, β-hydroxybutyrates, glycolates, maleates, tartrates, methanesulfonates, propanesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, mandelates, and other salts. In one embodiment, examples of pharmaceutically acceptable acid addition salts include those formed with mineral acids such as hydrochloric acid and hydrobromic acid, and in particular those formed with organic acids such as maleic acid.In some embodiments, bases commonly used to form pharmaceutically acceptable salts of any one of the compounds of the formulas include alkali metal hydroxides, including sodium, potassium, and lithium; alkaline earth metal hydroxides, such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia; organic amines, such as unsubstituted or hydroxyl-substituted mono-, di-, or tri-alkylamines and dicyclohexylamine; mono-, bis-, or tris-(2-OH-(C1-C6)-alkylamines), such as tributylamine, pyridine, N-methyl, N-ethylamine, diethylamine, triethylamine, N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; morpholine; thiomorpholine; piperidine; pyrrolidine; and amino acids, such as arginine and lysine. In some embodiments, any one of the compounds of the formulas disclosed herein or a salt thereof is substantially isolated. 【0339】 As used herein, the terms “individual” and “subject” are interchangeable and refer to any selected animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates, most preferably humans. 【0340】 The terms “protecting group” and “protective group” refer to a moiety that reversibly chemically modifies a functional group in order to obtain chemoselectivity or to reduce decomposition in one or more subsequent chemical reactions. Suitable protecting groups are well known in the art (see, for example, Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, NY, 1999, which is incorporated herein by reference in its entirety). 【0341】 As used herein, "color" refers to wavelengths of electromagnetic radiation visible to the human eye, and "colorless" refers to the absence of wavelengths of electromagnetic radiation visible to the human eye. [Examples] 【0342】 All starting materials / reagents / solvents were obtained from Sigma Aldrich, Thermo Fisher, VWR, TCI Chemicals, or Oakwood Chemicals and used without purification. Genipine was supplied by Herb-Sun Biotechnology. 【0343】 The following examples describe the synthesis of hydrogenated genipine derivatives and demonstrate the versatility and robustness of the 3,4-dihydro-2H-pyran moiety in binding to keratin tissue in in vitro tests utilizing lysine. The examples also demonstrate that the lysine conjugate is colorless. Some of the examples do not have the group b) moiety and therefore do not conform to the present invention. These examples help demonstrate that the 3,4-dihydro-2H-pyran moiety can be broadly substituted while retaining the described effects (ability to bind to skin and colorless in the bound state). 【0344】 Example 1 - Preparation of genipine derivative compound 1-hydroxy-7-methyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl (compound 1) 【0345】 [ka] 【0346】 Genipine (1-hydroxy-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate methyl) (1 equivalent) was added to a Schlenk flask with 10% Pd / C (10 wt%). The flask was changed between vacuum and nitrogen gas three times. In another flask, nitrogen was bubbled into methanol for 15 minutes. Once complete, methanol was slowly added to the Schlenk flask under a stream of nitrogen (0.05 M). The Schlenk flask was placed under vacuum and backpacked with H2 via a balloon. The reaction mixture was heated to 50°C and monitored by TLC until the starting materials were completely converted. The crude reaction mixture was filtered through a Celite pad and flushed with dichloromethane. The filtered solution was concentrated and isolated as a mixture of diastereomers by flash column chromatography. 【0347】 1 H NMR(300MHz,CDCl3)δ7.42(d,J=1.3Hz,1H),4.91(t,J=6.3Hz,1H),3.71(s,3H),2.89(m,1H),2.35-2.1 4(m,1H),2.11-1.94(m,1H),1.94-1.78(m,1H),1.64(m,1H),1.35-1.15(m,2H),1.11(d,J=6.7Hz,3H). HRMS(DART+):C 11 H 17 Calculated value for O4[M+H+]: 213.1121 m / z, measured value: 213.1124 m / z. 【0348】 Example 2 - Preparation of the hydrogenated genipine derivative compound 1-hydroxy-7-(hydroxymethyl)-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl (compound 2) 【0349】 [ka] 【0350】 Step 1-1-((tert-butyldimethylsilyl)oxy)-7-(((tert-butyldimethylsilyl)oxy)methyl)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate methyl 【0351】 [ka] Genipine (1 equivalent) was added to an oven-dried round-bottom flask along with tert-butyldimethylsilyl chloride (2.4 equivalents) and imidazole (5 equivalents). The reagents were then dissolved in dimethylformamide (0.3 M) and stirred at room temperature for 4 days. After completion, the crude reaction mixture was added to a separatory funnel along with ethyl acetate and brine. The organic phase was washed three times with brine. The combined aqueous layer was extracted twice with ethyl acetate. The combined organic phase was dried over magnesium sulfate and concentrated using a rotary evaporator. The title compound was isolated by flash column chromatography using a gradient of ethyl acetate and hexane. 【0352】 Step 2-1 Synthesis of ((tert-butyldimethylsilyl)oxy)-7-(((tert-butyldimethylsilyl)oxy)methyl)-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl 【0353】 [ka] The product from Step 1 (1 equivalent) was added to a Schlenk flask along with 10% Pd / C (10 wt%). The flask was changed between vacuum and nitrogen gas three times. In another flask, nitrogen was bubbled into methanol for 15 minutes. Once complete, methanol was slowly added to the Schlenk flask under a stream of nitrogen (0.05 M). The Schlenk flask was placed under vacuum and backpacked with H2 via a balloon. The reaction mixture was heated to 50°C and monitored by TLC until the starting materials were completely converted. The crude reaction mixture was filtered through a Celite pad and flushed with dichloromethane. The filtered solution was concentrated and isolated as a mixture of diastereomers by flash column chromatography. 【0354】 Step 3-1 Synthesis of 1-hydroxy-7-(hydroxymethyl)-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl The product from Step 2 (1 equivalent) was added to an oven-dried flask and dissolved in THF (0.04 M). TBAF (1 equivalent from a 1 M solution in THF) was added, and the reaction mixture was stirred for 1 hour. The crude reaction mixture was concentrated, and the desired compound (3) was isolated by flash column chromatography. 【0355】 1 H NMR(400MHz,MeOD)δ7.48(s,1H),3.70(s,3H),3.64-3.56(m,1H),3.51(m,1H) ,2.80-2.70(m,1H),2.27-2.07(m,2H),2.00-1.64(m,3H),1.50-1.19(m,3H). HRMS(DART+):C 11 H 17 Calculated value for O5[M+H+]: 229.1070 m / z, measured value: 229.1066 m / z. 【0356】 Example 3 - Preparation of genipine derivative compound 7-formyl-1-hydroxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl (compound 6) and genipine derivative compound 3-hydroxy-1,2a,2a1,3,4a,7a-hexahydro-2H-4,5-dioxacyclopenta[cd]indene-7-carboxylate methyl (compound 7) 【0357】 [ka] 【0358】 Step 1-7-(hydroxymethyl)-1-methoxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate methyl 【0359】 [ka] Genipine (1 equivalent) was added to a round-bottom flask and dissolved in methanol (0.05 M). Para-toluenesulfonic acid (0.3 equivalents) was added to the stirred genipine solution and reacted at room temperature until the starting materials were completely converted. Once complete, the crude product was concentrated using rotary evaporation and filtered through a silica plug. The crude product was flushed with dichloromethane and concentrated. The title compound was isolated by flash column chromatography. 【0360】 Step 2-7-Formyl-1-methoxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate methyl 【0361】 [ka] Dess-Martin periodinane (DMP) (1.2 equivalents) was added to a stirred solution of the product from Step 1 (1 equivalent) in dichloromethane. The reaction mixture was stirred for 24 hours. Once complete, saturated solutions of NaHCO3 and Na2S2O3 were sequentially added to the reaction mixture and stirred for 30 minutes. The two-phase mixture was added to a separatory funnel and extracted with dichloromethane / water (3×), followed by brine. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The crude material was dried and packed onto silica and purified by flash chromatography (hexane:ethyl acetate) to obtain the title compound. 【0362】 Step 3-7-Formyl-1-methoxy-1,4a,5,6,7,7a-Hexahydrocyclopenta[c]pyran-4-carboxylate methyl 【0363】 [ka] The product from Step 2 (1 equivalent) was added to a Schlenk flask along with 10% Pd / C (10 wt%). The flask was changed between vacuum and nitrogen gas three times. In another flask, nitrogen was bubbled into methanol for 15 minutes. Once complete, methanol was slowly added to the Schlenk flask under a stream of nitrogen (0.05 M). The Schlenk flask was placed under vacuum and backpacked with H2 via a balloon. The reaction mixture was heated to 50°C and monitored by TLC until the starting materials were completely converted. The crude reaction mixture was filtered through a Celite pad and flushed with dichloromethane. The filtered solution was concentrated and isolated as a mixture of diastereomers (title compound) by flash column chromatography. 【0364】 Step 4 - Synthesis of Compounds 6 and 7 The product from Step 3 was dissolved in acetic acid / 1M HCl / THF in a ratio of 3:2:5 to a total concentration of 0.07 M. The solution was stirred overnight at 60°C. Once complete, the solution was poured into a separatory funnel with water and ethyl acetate. The combined ethyl acetate extract was dried over sodium sulfate and concentrated under reduced pressure. The desired compound (as a 15:85 mixture of aldehyde compound 6 / acetal compound 7) was isolated by flash column chromatography (hexane:ethyl acetate). 【0365】 1 H NMR(400MHz,CDCl3)δ9.79(s,0.05H),9.97(s,0.11H)7.56-7.44(m,1H),6.07(d,J=5.9Hz,0.05H),5.90-5.82(m,0.55H),5 .74(d,J=5.0Hz,0.11H),5.36(d,J=4.9Hz,0.05H),5.11(d,J=1.6Hz,0.55H),5.03(d,J=1.5Hz,0.11H),4.91(d,J=7.5Hz,0. 15H),3.74(m,3H),3.61-3.55(m,0.05H),3.38(t,J=7.4Hz,0.05H),3.02(m,0.75H),2.94-2.78(m,1H),2.76-2.58(m,1.4H) ,2.56-2.43(m,0.20H),2.39-2.22(m,1H),2.06(m,0.25H),1.93-1.80(m,1H),1.72(m,1H),1.44(m,0.11H),1.15(m,0.8H). HRMS(DART+):C 11 H 15 Calculated value for O5[M+H+]: 227.0914 m / z, measured value: 227.0913 m / z. 【0366】 Example 4 - Synthesis of 1-hydroxy-4-(methoxycarbonyl)-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-7-carboxylic acid (compound 8) and 3-oxo-1,2a,2a1,3,4a,7a-hexahydro-2H-4,5-dioxacyclopenta[cd]indene-7-carboxylate methyl (compound 9) 【0367】 [ka] 【0368】 Step 1-1 Synthesis of methoxy-4-(methoxycarbonyl)-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-7-carboxylic acid 【0369】 [ka] The product from step 3 of Example 3 was dissolved in dimethylformamide (0.2 M) and stirred with 4 equivalents of potassium peroxymonosulfate for 48 hours. The crude product was added to a separatory funnel with ethyl acetate and brine. The combined ethyl acetate was dried over sodium sulfate, concentrated, and then isolated by flash column chromatography to obtain the title compound. 【0370】 Step 2 - Synthesis of Compound 8 and Compound 9 The product from Step 1 was dissolved in acetic acid / 1M HCl / THF in a ratio of 3:2:5 to a total concentration of 0.07M. The solution was stirred overnight at 60°C. Once complete, the solution was poured into a separatory funnel with water and ethyl acetate. The combined ethyl acetate extract was dried over sodium sulfate and concentrated. The title compound was isolated by flash column chromatography (hexane:ethyl acetate) to obtain the following desired compound. 【0371】 1 H NMR(400MHz,CDCl3)δ7.47(d,J=1.2Hz,1H),6.05(d,J=5.9Hz,1H),3.75(s,3H),3.41-3.32(m,1H),2.97(ddd,J=10.6,7.7,5.9Hz,1H),2. 93-2.81(m,1H),2.54-2.43(m,1H),2.26(dd,J=12.9,6.0Hz,1H),1.76(tdd,J=13.2,7.1,6.2Hz,1H),1.10(tdd,J=13.2,11.4,6.0Hz,1H). 13C NMR (101MHz, CDCl3) δ175.9,167.1,148.5,110.0,96.9,51.7,48.8,37.5,33.4,31.7,29.0. HRMS(DART+):C 11 H 13 Calculated value for O5[M+H+]: 225.0758 m / z, measured value: 225.0751 m / z. 【0372】 Example 5-(E)-1-hydroxy-7-(((4-(phenyldiazenyl)benzoyl)oxy)methyl)-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl (Compound 10) 【0373】 [ka] 【0374】 Step 1-7 Synthesis of methyl (hydroxymethyl)-1-methoxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate 【0375】 [ka] The compound obtained in step 3 of Example 3 (1 equivalent) was dissolved in methanol (0.27 M) and stirred at 0°C. Sodium borohydride (1.5 equivalents) was added. The reaction mixture was stirred for 30 minutes while warming to room temperature. Once complete, the crude reaction mixture was diluted with saturated NH4Cl and extracted with ethyl acetate (3×) in a separatory funnel. The combined organic phase was dried over sodium sulfate and concentrated under reduced pressure. The title compound was isolated by flash column chromatography. 【0376】 Step 2-(E)-1-Methoxy-7-(((4-(phenyldiazenyl)benzoyl)oxy)methyl)-1,4a,5,6,7,7a-Hexahydrocyclopenta[c]pyran-4-carboxylate methyl 【0377】 [ka] The compound obtained in Step 1 (1 equivalent) was dissolved in dichloromethane / pyridine (1:1 v / v) (0.2 M) and cooled to 0°C. 4-(phenylazo)benzoyl chloride (1.2 equivalents) was added dropwise at 0°C, and the mixture was reacted overnight while warming to room temperature. The crude reaction mixture was quenched with saturated sodium bicarbonate and extracted with dichloromethane and water in a separatory funnel. The combined DCM layers were dried over sodium sulfate, concentrated under reduced pressure, and isolated by flash column chromatography to obtain the title compound. 【0378】 Step 3 - Synthesis of the title compound of this embodiment The product from Step 2 was dissolved in a 3:2:5 ratio of k-acetic acid / 1M HCl / THF at a total concentration of 0.07 M. The solution was stirred overnight at 60°C. Once complete, the solution was poured into a separatory funnel with water and ethyl acetate. The combined ethyl acetate extract was dried over sodium sulfate and concentrated under reduced pressure. The title compound was isolated by flash column chromatography (hexane:ethyl acetate) to obtain the desired compound (10). 【0379】 1 H NMR(300MHz,CDCl3)δ8.22-8.15(m,2H),7.99-7.91(m,4H),7.59-7.50(m,3H),7.45(m,1H),5.66(t,J=3. 7Hz,0.3H),5.19-5.09(m,0.65H),4.69(dd,J=11.2,7.3Hz,0.65H),4.56(d,J=8.0Hz,0.6H),4.46(dd,J= 11.3,7.4Hz,0.6H),3.74(s,3H),3.69(m,1H),3.63-3.55(m,2H),3.08(m,0.3H),2.98(m,0.7H),2.79(m, 1H),2.45-2.18(m,2H),2.12-2.03(m,0.6H),1.95-1.81(m,2H),1.79-1.59(m,3H),1.55-1.41(m,0.6H). HRMS(DART+):C 24 H 25Calculated value for N2O6[M+H+]: 437.1707 m / z, measured value: 437.1714 m / z. 【0380】 Example 6 - Conjugation of lysine and color properties of genipine hydride A genipine hydride derivative (compound 1) was conjugated with lysine to obtain compound 1-lysine conjugate. 【0381】 [ka] 【0382】 As shown in Figure 5, when anchor compound 1 is reacted with an amino acid to mimic skin binding, the compound's strong UV absorption (absorption at wavelengths below 410 nm) shifts slightly, but there is no visible color (no absorption at wavelengths above 410 nm). 【0383】 Figure 6A shows that reacting anchor compound 2 with lysine to mimic skin binding results in strong UV light absorption and no visible color. 【0384】 Figure 6B shows that reacting anchor compounds 6 / 7 with lysine to mimic skin binding results in UV light absorption and does not produce visible color. 【0385】 Figure 6C shows that reacting anchor compounds 8 / 9 with lysine to mimic skin binding results in UV light absorption and does not produce visible color. 【0386】 The azo dye compound (compound 10) from Example 5 was conjugated with lysine to obtain a conjugate. 【0387】 [ka] 【0388】 As shown in Figure 6D, the pigment conjugate of the anchor compound reacts with amino acids to mimic skin binding, resulting in color due to the presence of the azo pigment moiety. However, the conjugation process does not alter the absorbance properties of the compound before conjugation with lysine. 【0389】 All of the above examples are C1-C of group b). 60 This disclosure is inconsistent with the present disclosure due to the absence of certain parts. 【0390】 Example 7-1-Hydroxy-7-(((2-hydroxybenzoyl)oxy)methyl)-1,4a,5,6,7,7a-Hexahydrocyclopenta[c]pyran-4-carboxylate methyl 【0391】 [ka] 【0392】 Step 1-7 Synthesis of methyl (hydroxymethyl)-1-methoxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate 【0393】 [ka] The compound obtained in step 3 of Example 3 (1 equivalent) was dissolved in methanol (0.27 M) and stirred at 0°C. Sodium borohydride (1.5 equivalents) was added. The reaction mixture was stirred for 30 minutes while warming to room temperature. Once complete, the crude reaction mixture was diluted with saturated NH4Cl and extracted with ethyl acetate (3×) in a separatory funnel. The combined organic phase was dried over sodium sulfate and concentrated under reduced pressure. The title compound was isolated by flash column chromatography. 【0394】 Step 2-7 Synthesis of (((2-acetoxybenzoyl)oxy)methyl)-1-methoxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate methyl 【0395】 [ka] The product from Step 1 (1 equivalent) was dissolved in dichloromethane / pyridine (1:1 v / v) (0.2 M) and cooled to 0°C. O-acetylsalicyroyl chloride (1.2 equivalents) was added dropwise at 0°C and the mixture was reacted overnight while warming to room temperature. The crude reaction mixture was quenched with saturated sodium bicarbonate and extracted with dichloromethane and water in a separatory funnel. The combined DCM layers were dried over sodium sulfate, concentrated under reduced pressure, and isolated by flash column chromatography to obtain the title compound. 【0396】 Step 3 - Synthesis of the title compound of this embodiment The product from Step 2 was dissolved in acetic acid / 1M HCl / THF in a ratio of 3:2:5 to a total concentration of 0.07 M. The solution was stirred overnight at 60°C. Once complete, the solution was poured into a separatory funnel with water and ethyl acetate. The combined ethyl acetate extract was dried over sodium sulfate and concentrated under reduced pressure. The title compound was isolated by flash column chromatography (hexane:ethyl acetate) to obtain the desired compound. 【0397】 1 H NMR(400MHz,CDCl3)δ10.79(s,0.25H),10.77(s,0.6H),7.84(m,1H),7.49-7.45(m,2H),7.01(m,1 H),6.91(m,1H),5.65(t,J=3.6Hz,0.25H),5.15(dd,J=8.5,6.5Hz,0.7H),4.67(dd,J=11.1,7.2Hz, 0.7H),4.58(d,J=8.2Hz,0.5H),4.48(dd,J=11.2,7.6Hz,0.7H),3.76(m,3H),3.34(m,0.7H),3.00( m,1H),2.95-2.68(m,1H),2.46-2.30(m,1H),2.26(m,0.7H),2.18-1.89(m,1H),1.83-1.43(m,2H). HRMS(DART+):C 18 H 24Calculated value for NO7[M+NH+]: 366.1547 m / z, measured value: 366.1550 m / z. 【0398】 Example 8 - Conjugation with lysine The compound from Example 7 was conjugated with lysine to obtain a lysine conjugate. 【0399】 [ka] 【0400】 As shown in Figure 7, when the compound from Example 7 (i.e., hydrogenated genipin salicylate, referred to as "genipin salicylate" in Figure 7) is reacted with the amino acid lysine (referred to as "amine" in Figure 7) to mimic skin binding, the UV absorption peak shifts slightly (no visible color is produced). 【0401】 Example 9 - Preparation and conjugation with lysine 【0402】 [ka] 【0403】 The aldehyde obtained as described in International Publication No. 2022 / 036113(A1) was weighed and transferred to a round-bottom flask. MeOH (0.2 M) was added and stirred until completely solubilized. DOWEX® 50WX8 was first washed with methanol and dried under vacuum. After drying, DOWEX® 50WX8 (H+ type) was added to the stirred aldehyde solution. The mixture was heated at 40°C for 65 hours. After completion, methanol was removed by rotary evaporation and the product was precipitated with ether / hexane to obtain a white powder. 【0404】 [ka] 【0405】 The obtained aldehyde was added to a 0.2 M DMF solution of Oxon® (potassium peroxymonosulfate; 4 equivalents), and the reaction mixture was stirred at room temperature for 4 days. The crude mixture was added to a separatory funnel along with ethyl acetate and brine. The aqueous layer was thoroughly washed with ethyl acetate. The combined ethyl acetate layer was then extracted with saturated NHCO3 (3×). The combined aqueous basic layer was re-acidified with concentrated HCl until the pH was less than 7. The acidified solution was then extracted with ethyl acetate (3×). The combined ethyl acetate layer was dried over Na2SO4 and concentrated. 【0406】 [ka] 【0407】 1-chloro-N,N-2-trimethyl-1-propenylamine was added to a 0.25 M MeCN solution of carboxylic acid over 1 hour at 0°C. After the starting material was consumed (confirmed by TLC), the mixture was concentrated to an oily consistency under vacuum. After concentration, dichloromethane was added to the reaction mixture (0.2 M) and stirred at 0°C. 1-decanol and then pyridine (equal volume to dichloromethane) were added. The ice bath was removed and the mixture was warmed to room temperature over 1 hour. After completion, the reaction product was diluted with DCM and transferred to a separatory funnel. Pyridine was removed by washing with 1 M HCl (2×). Unreacted acylchloride was removed by washing with saturated NaHCO3 (1×). The mixture was dried over sodium sulfate and concentrated to dryness. The resulting substance was purified by flash column chromatography using an ethyl acetate and hexane gradient. 【0408】 [ka] 【0409】 10% palladium carbon (10 wt%) was weighed into an oven-dried Schlenk flask. The flask was changed between argon and vacuum three times. Toluene was added to another Erlenmeyer flask equipped with a stirring rod. A needle connected to a hose on the argon line was submerged in the toluene and bubbled through the solvent for 15 minutes. Meanwhile, the ester material was weighed into a vial. After toluene aeration was complete, the ester starting material was dissolved in degassed toluene. This solution was carefully added to the Schlenk flask under an argon stream. After completion, a rubber septum was placed on top of the Schlenk flask, evacuated under vacuum, and then left under static vacuum. H2 was packed into a balloon and an 18G needle was attached. The balloon was added to the reaction flask, warmed to 50°C, and reacted for 24 hours. The crude reaction product was not further purified before proceeding to the next step. 【0410】 [ka] 【0411】 The reduced ester starting material was deprotected over a long period of heating using an HCl / acetic acid mixture in tetrahydrofuran. The crude reaction mixture was added to a separatory funnel and carefully quenched with a saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The combined organic phase was dried over sodium sulfate and concentrated under vacuum. The crude material was isolated by flash column chromatography using an ethyl acetate and hexane gradient. 【0412】 HRMS(DART+):C 21 H 35 O6[M+H + Calculated value for ]: 383.2428 m / z, measured value: 383.2420 m / z 1¹H NMR (400MHz, CDCl3) of the diastereomer mixture: δ 7.45 (m, 1H - integrated with the mixture as 1), 5.51 (d, J=8.0Hz, 0.33H), 5.34-4.72 (m, 1H), 4.18-4.00 (m, 2H), 3.71 (s, 3H), 3.12 (m 0.36H), 3.07-2.87 (m, 1H), 2.80 (m, 1H), 2.69-2.39 (m, 1H), 2.32 (m, 1H), 2.10-1.92 (m, 2H), 1.92-1.76 (m, 1H), 1.63 (m 2H), 1.48-1.18 (m, 15H), 0.94-0.82 (m, 3H). 【0413】 [ka] 【0414】 The deprotected species from the previous step was reacted with L-lysine (2 molar equivalents) in MeOH (0.05 M) containing a few drops of water, and the mixture was stirred at 35°C for 18 hours. 【0415】 HRMS(DART+):C 27 H 45 N2O6[M+H + Calculated value for ]: 493.3272 m / z, measured value: 493.3267 m / z. 【0416】 As shown in Figure 8, the obtained lysine conjugate (B) was almost colorless (very pale yellow). 【0417】 Example 10 - Preparation of genipine hydrogenated derivative linked to glycerol and its conjugation to lysine Synthesis of starting materials: 【0418】 [ka] 【0419】 Equimolar amounts of phenylboronic acid were added to a stirred solution (0.5 M) of glycerol in toluene. The mixture was heated under reflux for 5 hours, and the reaction mixture was concentrated by rotary evaporation. Fresh toluene was added three times, and excess water was removed by evaporation. The resulting glycerolboronic acid ester was a mixture of isomers and was moved to the next step. 【0420】 [ka] 【0421】 Step 1: O-benzyl protection of genipin: 7-(hydroxymethyl)-1-methoxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate benzyl Genipine (1 equivalent) was added to a round-bottom flask and dissolved in benzyl alcohol / dichloromethane (1 / 1 v / v) (0.5 M). Dowex® 50WX8 (20 wt%) was added to the stirred genipine solution and reacted at 40°C until the starting materials were completely converted. After completion, the crude product was filtered to remove the Dowex® resin and then concentrated by rotary evaporation. The title compound was isolated by flash column chromatography. 【0422】 Step 2: Oxidation of o-benzyl-protected genipin: 7-formyl-1-methoxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate benzyl A 0.5 M stirred solution of benzyl-protected genipin in acetonitrile was to which 20 mol% CuBr, 2,2'-bipyridyl, and a TEMPO catalyst species were added. The contents were vigorously stirred in a flask open to air until the starting materials were completely transformed. The title compound was isolated by flash column chromatography. 【0423】 Step 3: Oxidation to carboxylic acid The product from Step 2 was dissolved in dimethylformamide (0.2 M) and stirred with 4 equivalents of potassium peroxymonosulfate for 48 hours. The crude product was added to a separatory funnel with ethyl acetate and washed with brine (3x). The aqueous phase was then back-extracted with ethyl acetate (3x). The combined ethyl acetate was dried over sodium sulfate, concentrated, and isolated by flash column chromatography to obtain the title compound. 【0424】 [ka] 【0425】 Step 1: Acylation of genipine carboxylate derivative To a dry MeCN solution of carboxylic acid (0.25 M), 1-chloro-N,N-2-trimethyl-1-propenylamine (1.2 equivalents) was added at 0°C and the mixture was stirred for 1 hour while warming to room temperature. After the starting material was consumed (confirmed by TLC), the mixture was concentrated to an oily state under vacuum. After concentration, dry dichloromethane was added to the reaction mixture (0.2 M) and stirred at 0°C. Glycerol-phenylboronic acid ester was added, followed by pyridine (equal volume to dichloromethane). The ice bath was removed and the mixture was warmed to room temperature over 1 hour. After completion, the reaction product was diluted with DCM and transferred to a separatory funnel. Pyridine was removed by washing with 1 M HCl (2×). The DCM was concentrated, resuspended in ethyl acetate, and then washed with 1 M D-sorbitol / 1 M Na2CO3 (3×) to cleave the boronic acid ester and remove phenylboronic acid. The combined aqueous phase was back-extracted with ethyl acetate, dried with sodium sulfate, and concentrated to dryness. The resulting crude substance was purified by flash column chromatography using an ethyl acetate and pentane gradient. 【0426】 Step 2: Reduction and deprotection of acylated genipine derivatives 10% palladium carbon (10 wt%) was weighed into an oven-dried Schlenk flask. The flask was changed between argon and vacuum three times. Methanol was added to another Erlenmeyer flask equipped with a stirring rod. A needle connected to a hose on the argon line was submerged in the methanol and bubbled through the solvent for 15 minutes. Meanwhile, the ester material was weighed into a vial. After methanol aeration was complete, the ester starting material was dissolved in degassed methanol. This solution was carefully added to the Schlenk flask under an argon stream. After completion, the rubber septum was placed on top of the Schlenk flask, evacuated under vacuum, and then left under static vacuum. The balloon was filled with H2 and fitted with an 18G needle. The balloon was added to the reaction flask, warmed to 50°C, and reacted for 24 hours. The crude reaction product was purified by flash column chromatography using a dichloromethane and methanol gradient. 【0427】 [ka] 【0428】 1H NMR(400MHz,MeOD)Main diastereomer δ7.48(s,1H),4.89(d,J=7.8Hz,1H),4.23-4.06(m,2H),3.84(m,1H),3.70(s,3H),3.69-3.6 2(m,1H),3.56(dd,J=5.5,2.1Hz,2H),2.89(m,2H),2.38(m,1H),2.32-2.18(m,1H),2.05(m,1H),1.84(m,1H),1.41(m,1H). 【0429】 13 ¹³C NMR (101 MHz, MeOD): Major diastereomers δ: 177.0, 169.6, 154.2, 110.9, 96.2, 71.1, 66.8, 64.0, 51.7, 46.8, 46.6, 36.9, 33.9, 29.4. 【0430】 HRMS(DART+):C 14 H 24Calculated value for NO8[M+NH4+]: 334.1496 m / z, measured value: 334.1503 m / z 【0431】 [ka] 【0432】 The deprotected species from the previous step was reacted with L-lysine (2 molar equivalents) in MeOH (0.05 M) containing a few drops of water, and the mixture was stirred at 35°C for 18 hours. 【0433】 HRMS(ESI+):C 20 H 31 N2O8[M+H+]:427.2075m / z 【0434】 As shown in Figure 9, the obtained lysine conjugate was almost colorless (very pale yellow). 【0435】 Examples 11 - Conjugation of the compounds of Example 10 into the skin A 100 mM methanol solution of the genipine hydrogenate derivatives obtained in Examples 9 and 10 was prepared, and 200 μL of each solution was drop-cast onto porcine skin explants. Methanol was applied to the third spot as a control. The genipine hydrogenate derivatives were bound to the skin in a hydration chamber for 2 hours. The porcine skin pieces were then removed from the chamber and thoroughly washed with water to remove any remaining unreacted genipine hydrogenate derivatives. 【0436】 As shown in Figure 10, the pig's skin did not visually change under normal daylight, but exposure to UV light revealed that the genipin hydrogenate derivative bound to the skin. 【0437】 Example 12 - Preparation of a hydrogenated genipine derivative linked to picaridin and its conjugation to lysine 【0438】 [ka] 【0439】 Step 1: Acylation of genipine carboxylate derivative To a dry MeCN solution of carboxylic acid (0.25 M), 1-chloro-N,N-2-trimethyl-1-propenylamine (1.2 equivalents) was added over 1 hour at 0°C. After the starting material was consumed (confirmed by TLC), the mixture was concentrated to an oily state under vacuum. After concentration, dry dichloromethane was added to the reaction mixture (0.2 M) and stirred at 0°C. Icaridin and then pyridine (equal volume to dichloromethane) were added. The ice bath was removed and the mixture was warmed to room temperature over 1 hour. After completion, the reaction product was diluted with DCM and transferred to a separatory funnel. Pyridine was removed by washing with 1 M HCl (2×). Unreacted acylchloride was removed by washing with saturated NaHCO3 (1×). The mixture was dried over sodium sulfate and concentrated to dryness. The resulting substance was purified by flash column chromatography using an ethyl acetate and pentane gradient. 【0440】 Step 2: Reduction and deprotection of acylated genipine derivatives 10% palladium carbon (10 wt%) was weighed into an oven-dried Schlenk flask. The flask was changed between argon and vacuum three times. Methanol was added to another Erlenmeyer flask equipped with a stirring rod. A needle connected to a hose on the argon line was submerged in the methanol and bubbled through the solvent for 15 minutes. During this time, the ester material was weighed into a vial. After methanol aeration was complete, the ester starting material was dissolved in degassed methanol. This solution was carefully added to the Schlenk flask under an argon stream. After completion, a rubber septum was placed on top of the Schlenk flask, evacuated under vacuum, and then left under static vacuum. A balloon was filled with H2 and fitted with an 18G needle. The balloon was added to the reaction flask, warmed to 50°C, and reacted for 24 hours. The crude reaction product was purified by flash column chromatography using an ethyl acetate and pentane gradient. 【0441】 [ka] 【0442】 1 H NMR (400MHz, DMSO) Mixture of diastereomers δ7.50-7.30(m,2H),5.39-4.79(m,1H),4.59(m,1H),4.28(br s,1H),3.98(m,2H),3.86(d,J=13.8Hz,1H),3.62(s,3H),2.87-2.65(m,3H),2.25(m,1H),2.16-1.8 3(m,3H),1.80-1.65(m,2H),1.63-1.42(m,7H),1.42-1.18(m,2H),1.17-1.04(m,3H),0.83(m,3H). 【0443】 13 ¹³C NMR (101MHz, DMSO) Major diastereomers δ: 174.6, 166.9, 154.5, 152.6, 108.9, 94.6, 72.1, 61.9, 50.9, 44.9, 44.7, 38.4, 35.1, 32.2, 28.5, 28.4, 28.1, 27.9, 25.1, 19.5, 19.5, 18.5, 9.5. 【0444】 HRMS(DART+):C 23 H 36 Calculated value for NO8[M+H+]: 454.2435 m / z, measured value: 454.2445 m / z. 【0445】 The deprotected species from the previous step was reacted with L-lysine (2 molar equivalents) in MeOH (0.05 M) containing a few drops of water, and the mixture was stirred at 35°C for 18 hours. 【0446】 [ka] 【0447】 HRMS(ESI+):C 29 H 46 Calculated value for N3O8[M+H+]: 564.3279 m / z, measured value: 564.3290 m / z 【0448】 As shown in Figure 11, the obtained lysine conjugate was almost colorless (very pale yellow). 【0449】 Example 13 - Conjugation of the compound from Example 12 into the skin A 50 mM methanol solution of the genipine hydrogenate derivative from Example 11 was prepared, and 100 μL of the solution (containing 2.2 mg of genipine hydrogenate derivative) was drop-cast onto explanted pig skin. The genipine hydrogenate derivative was allowed to bind to the skin under ambient conditions for 2 hours. The pig skin samples were then cleaned by wiping and scrubbing with a damp paper towel to remove any remaining unreacted genipine hydrogenate derivative. Binding of the compound to the pig skin was confirmed by UV light. After 24 hours, the pig skin was immersed in water, then removed, dried, and scrubbed again. Exposure to UV light reconfirmed that the genipine hydrogenate derivative from Example 11 had stably bound to the skin. 【0450】 As shown in Figure 12, pig skin did not visually change under normal daylight, but exposure to UV light revealed that the genipin hydrogenate derivative was bound to the skin at the aforementioned 2-hour and 24-hour intervals. 【0451】 Example 14 - Preparation of a hydrogenated genipine derivative linked to D-glucose using an ethylene glycol linker and its conjugation to lysine. 【0452】 [ka] 【0453】 Steps 1 and 2: Acylation of genipine carboxylate derivatives: To a dry MeCN solution of carboxylic acid (0.25 M), 1-chloro-N,N-2-trimethyl-1-propenylamine (1.2 equivalents) was added over 1 hour at 0°C. After the starting material was consumed (confirmed by TLC), the mixture was concentrated to an oily state under vacuum. After concentration, dry dichloromethane was added to the reaction mixture (0.2 M) and stirred at 0°C. A glucose derivative (shown above) was added, followed by pyridine (equivalent volume to dichloromethane) (0.2 M). The ice bath was removed, and the mixture was warmed to room temperature over 1 hour. After completion, the reaction product was diluted with DCM and transferred to a separatory funnel. Pyridine was removed by washing with 1 M HCl (2×). Unreacted acylchloride was removed by washing with saturated NaHCO3 (1×). The mixture was dried over sodium sulfate and concentrated to dryness. The resulting substance was purified by flash column chromatography using an ethyl acetate and pentane gradient. 【0454】 Step 3: Selective deprotection of acetyl protecting groups The acetyl-protected product from Step 2 was dissolved in methanol (0.2 M), and then selectively deprotected by adding 4.1 equivalents of n-hexylamine and stirring at 50°C for 2 hours. The resulting deprotected product was isolated by flash column chromatography using a methanol and dichloromethane gradient. 【0455】 Step 4: Reduction and deprotection of acylated genipine derivatives 10% palladium carbon (10 wt%) was weighed into an oven-dried Schlenk flask. The flask was changed between argon and vacuum three times. Methanol was added to another Erlenmeyer flask equipped with a stirring rod. A needle connected to a hose on the argon line was submerged in the methanol and bubbled through the solvent for 15 minutes. Meanwhile, the ester material was weighed into a vial. After methanol aeration was complete, the ester starting material was dissolved in degassed methanol. This solution was carefully added to the Schlenk flask under an argon stream. After completion, the rubber septum was placed on top of the Schlenk flask, evacuated under vacuum, and then left under static vacuum. The balloon was filled with H2 and fitted with an 18G needle. The balloon was added to the reaction flask, warmed to 50°C, and reacted for 24 hours. The crude reaction product was purified by flash column chromatography using a methanol and dichloromethane gradient. 【0456】 [ka] 【0457】 HRMS(ESI+):C 19 H 28 O 12 Calculated value for Na[M+Na+]: 471.1473 m / z, measured value: 471.1470 m / z. 【0458】 [ka] 【0459】 The deprotected species from the previous step was reacted with L-lysine (2 molar equivalents) in MeOH (0.05 M) containing a few drops of water, and the mixture was stirred at 35°C for 18 hours. 【0460】 HRMS(DART+):C 25 H 38 N2O 12 Calculated value for [M+H+]: 559.2498 m / z, Measured value: 559.2508 m / z The resulting lysine conjugate was almost colorless (very pale yellow). 【0461】 Other Embodiments While the present invention has been described along with embodiments for carrying it out, it should be understood that the foregoing description is illustrative and not intended to limit the scope of the invention as defined by the attached claims. Other embodiments, advantages, and modifications are within the scope of the claims below. 【0462】 This disclosure also relates to the following embodiments which supplement the above specification and may be freely combined with it. 1. A topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound suitable for covalent bonding to the skin is a compound of formula (I), 【0463】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Consistent with acting as a skin moisturizer, insecticide, skin whitening agent, or pharmaceutical, and / or b2) After cleavage from the 3,4-dihydro-2H-pyran moiety, it is configured to act as a skin moisturizer, insecticide, skin whitening agent, fragrance, or pharmaceutical. L1-A1 and L2-A2 are topical compositions that do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. 2. Group b) C1-C 60 The part or polymer part is its C1-C 60 The topical composition according to Embodiment 1, comprising a functional group that binds to the corresponding L1, L2, or L3 portion, or, if the corresponding L1, L2, or L3 portion is absent, to the 3,4-dihydro-2H-pyran portion. 3. The topical composition according to Embodiment 2, wherein the functional group comprises a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, or a combination thereof, more specifically, a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof, particularly a carbon atom and / or an oxygen atom. 4. Functional groups are, 1 to 12 carbon atoms, more specifically 1 to 6 carbon atoms, and especially 1 to 3 carbon atoms; 1 to 12 oxygen atoms, more specifically 1 to 6 oxygen atoms, and especially 1 to 3 oxygen atoms; 1 to 4 nitrogen atoms, more specifically 1 to 3 nitrogen atoms, and especially 1 to 2 nitrogen atoms; One to three sulfur atoms, more specifically one to two sulfur atoms, and especially one sulfur atom; The topical composition according to Embodiment 3, comprising one or more, two or more, three or more, four or more, or all of 1 to 3 phosphorus atoms, more specifically 1 to 2 phosphorus atoms, and especially 1 phosphorus atom. 5. The topical composition according to any one of Embodiments 2 to 4, wherein the functional groups are cleavable under physiological conditions after application of the topical composition to the skin. 6. A topical composition according to any one of Embodiments 2 to 5, wherein the functional group is hydrolyzable at the physiological pH of mammalian skin, more specifically human skin, particularly at a pH of about 5 to about 6. 7. The topical composition according to any one of Embodiments 2 to 6, wherein the functional groups are enzymatically cleavable under physiological conditions after application of the topical composition to the skin, and in particular enzymatically cleavable by enzymes present in human skin. 8. A topical composition according to any one of Embodiments 2 to 7, wherein the functional group is configured to be cleaved into a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonate, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefin, an oxime, or a salt thereof. 9. The functional groups are hydroxyl groups, primary or secondary amine groups, carboxylic acids, thiols, aldehydes, ketones, thiocarbonates, sulfonic acids, sulfinic acids, phosphoric acids, phosphonic acids, olefins, olefins, or oximes, or salts thereof, from group b) C1-C 60 A topical composition according to any one of Embodiments 2 to 8, configured to provide a corresponding L1, L2, or L3 portion bound to a partial or polymer portion, or, if no corresponding L1, L2, or L3 portion exists, to a 3,4-dihydro-2H-pyran portion after cleavage. 10. The functional groups are hydroxyl groups, primary or secondary amine groups, carboxylic acids, thiols, aldehydes, ketones, thiocarbonates, sulfonic acids, sulfinic acids, phosphoric acids, phosphonic acids, olefins, or oximes, or salts thereof, after cleavage, C1-C of group b) 60 A topical composition according to any one of embodiments 2 to 8, configured to be provided to a portion or a polymer portion. 11. Functional groups include carbon esters, especially monoesters, 1,1-diesters, carbonates, or carbamates; ethers or thioethers, especially acetals, hemiacetals, glycoside groups, or thioacetals; and carbon amides, especially peptides or N- A topical composition according to any one of Embodiments 2 to 10, comprising a Mannich base; enol; enamine; imine; oxime; sulfate ester; sulfonic acid ester; sulfonic acid amide; phosphate ester; phosphonic acid ester; phosphate amide; or phosphonic acid amide. 12. A1 is C1~C of group b). 60 A topical composition according to any one of Embodiments 1 to 11, representing a portion or polymer portion. 13. A2 is C1~C of group b). 60 A topical composition according to any one of Embodiments 1 to 12, representing a portion or polymer portion. 14. A3 is C1-C of group b). 60 A topical composition according to any one of Embodiments 1 to 13, representing a portion or polymer portion. 15. The remaining parts of A1, A2, and A3 are C1-C 30 A topical composition according to any one of embodiments 12 to 14, representing a partial H, hydroxyl, amino, or halogen. 16. L1 represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optional substituent, and / or L2 represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optional substituent, and / or The topical composition according to any one of Embodiments 1 to 15, wherein L3 is present and represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optionally substituted substituent. 17. L1 represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optionally substituted substituent, and the functional group is bonded to L1 and / or L2 represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optional substituent, and the functional group is bonded to L2 and / or A topical composition according to any one of Embodiments 2 to 15, wherein L3 is present and represents an optionally substituted hydrocarbon moiety containing 1 to 8 carbon atoms in combination with its optionally substituted substituent, and the functional group is bonded to L3. 18. A topical composition according to any one of Embodiments 1 to 17, wherein L1 and L2 are present and form a 5-membered ring, a 6-membered ring, a 7-membered ring, or an 8-membered ring, in particular cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, tetrahydrofuranil, or tetrahydropyranil. 19. L1 and L2 are present and optionally substituted to form a 5-membered or 6-membered ring, particularly cyclopentyl or cyclohexyl, where A1 and A2 are -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - The topical composition according to Embodiment 18, wherein a group selected from a combination thereof is optionally bonded via the group. 20. L1 and L2 are present and form a cyclopentyl ring, cyclopentenyl ring, cyclohexyl ring, or cyclohexenyl ring, and A1 and A2 are -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - The topical composition according to Embodiment 18, wherein a group selected from a combination thereof is optionally bonded via the group. 21. A1 is C1~C of group b). 60 A topical composition according to Embodiment 20, representing a portion or polymer portion. 22. A3 is C1~C of group b). 60 A topical composition according to Embodiment 20 or Embodiment 21, representing a portion of the composition. 23. A2 is C1~C 30 A topical composition according to Embodiment 21 or Embodiment 22, wherein a portion represents H, hydroxyl, amino, or halogen, particularly hydrogen. 24. C1-C of group a)30 A topical composition according to any one of Embodiments 1 to 23, comprising: 1 to 30, more specifically 1 to 16, particularly 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, particularly 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, particularly 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, particularly 0 to 3 phosphorus atoms; and 0 to 10, more specifically 0 to 8, particularly 0 to 6 halogen atoms. 25. C1~C 30 The part is selected from saturated or unsaturated, cyclic or acyclic (hetero)alkyl groups, and / or C1-C1 30 The topical composition according to Embodiment 24, wherein the portions are bonded to L1, L2, and L3, respectively, via carbon atoms, oxygen atoms, nitrogen atoms, or sulfur atoms. 26. A3 is C1~C of group a) 30 A selection of saturated or unsaturated cyclic or acyclic (hetero)alkyl C1-C2 atoms, comprising a portion, more specifically 1-16, more specifically 1-12, and especially 1-8 carbon atoms; 0-6, more specifically 0-4, and especially 0-3 oxygen atoms; 0-6, more specifically 0-4, and especially 0-3 nitrogen atoms; 0-6, more specifically 0-4, and especially 0-3 sulfur atoms; and 0-6, more specifically 0-4, and especially 0-3 halogen atoms. 16 A topical composition according to any one of embodiments 1 to 25, representing a portion of the composition. 27. A3 is C1-C selected from carboxylic acids or their salts; carboxylic acid esters; or ketones. 16 A topical composition according to embodiment 26, representing a portion of the composition. 28. A3 is a C1-C4 alkyl carboxylic acid or its salt; a C1-C4 alkyl carboxylic acid ester; or a C1-C4 alkyl carbonyl ester selected from C1-C4 alkylcarbonyl. 16 A topical composition according to embodiment 26, representing a portion of the composition. 29. L1 and OR 1 The topical composition according to any one of Embodiments 1 to 28, wherein the carbon atoms to which they are bonded together form a five-membered or six-membered lactone. 30. R 1 is hydrogen, C 1~6 Acyl, or C 1~6 A topical composition according to any one of Embodiments 1 to 29, wherein alkyl, particularly hydrogen, is represented. 31. At least one of A1, A2, and A3 is C1-C of group b1). 60 A topical composition according to any one of Embodiments 1 to 30, representing a portion or polymer portion. 32. At least one of A1, A2, and A3 is C1-C of group b2). 60 A topical composition according to any one of Embodiments 1 to 31, representing a portion or polymer portion. 33. Compounds that can covalently bond to the skin are those of formula (II), 【0464】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 L3, A1, and A3 are as defined in any one of Embodiments 1 to 32, (R 2 ) n Each represents n parts independently selected from H, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, amino, or halogen. n is an integer selected from 1 and 2. L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - is one of the bases selected from R 4 The topical composition according to any one of Embodiments 1 to 32, wherein H or C1-C4 alkyl is selected. 34. Compounds that can covalently bond to the skin are those of formula (III), 【0465】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 L3, A1, and A3 are as defined in any one of Embodiments 1 to 32, L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - is one of the bases selected from R 4 The topical composition is selected from H or C1-C4 alkyl, as described in any one of Embodiments 1 to 33. 35. Compounds that can covalently bond to the skin are those of formula (IV), 【0466】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 And A1 is as defined in any one of Embodiments 1 to 32, (R 2 ) nEach represents n parts independently selected from H, C1-C4 alkyl, C1-C4 alkoxyl, hydroxyl, amino, or halogen. n is an integer selected from 1 and 2. L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - is one of the bases selected from R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R 4 The topical composition is selected from H or C1-C4 alkyl, as described in any one of Embodiments 1 to 33. 36. R 3 The topical composition according to Embodiment 35, wherein is a C1-C4 alkyl moiety or phenyl. 37. Compounds that can covalently bond to the skin are those of formula (V), 【0467】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 And A1 is as defined in any one of Embodiments 1 to 32, L4 is either absent, or -O-, -S-, -C(O)-, -CO2-, -OC(O)-, -NR 4 -, -NR 4 -C(O)-, -C(O)-NR 4 -,-(CH2) 1~4 -,-(CH2) 1~4 -O- and -O-(CH2) 1~4 - is one of the bases selected from R 3This is as defined in Embodiment 35 or Embodiment 36, R 4 The topical composition is selected from H or C1-C4 alkyl, as described in any one of Embodiments 1 to 34. 38. At least one of A1, A2, and A3 is configured to act as a skin moisturizer and / or to act as a skin moisturizer after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 A topical composition according to any one of Embodiments 1 to 37, comprising a portion or a polymer portion. 39. C1~C 60 The topical composition according to Embodiment 38, wherein the partial or polymer portion comprises a plurality of hydrogen bonding groups selected from the group consisting of hydroxyl groups, ether groups, carboxylic acids, amines and amides, and salts thereof. 40. The topical composition according to Embodiment 39, wherein the multiple hydrogen bonding groups include three or more, more specifically four or more, and particularly six or more hydrogen bonding groups. 41. C atom, C1~C 60 The topical composition according to Embodiment 39 or Embodiment 40, wherein the ratio of the total hydrogen bonding groups contained in the portion is about 4:1 to 1:1, more specifically about 3:1 to about 1:1, and particularly about 2:1 to about 1:1. 42. C1~C 60 A topical composition according to any one of embodiments 38 to 41, wherein the portion has a molecular weight of at least 60 g / mol, more specifically at least 90 g / mol, and particularly at least 120 g / mol. 43. C atom, C1~C 60 The ratio of the heteroatoms contained in the portion to the total is about 4:1 to 1:2, more specifically about 3:1 to about 1:1.5, and in particular about 2:1 to about 1:1, and the heteroatoms are selected from nitrogen and oxygen, as described in any one of embodiments 38 to 42 of the topical composition. 44. C1~C 60 The part is, Polyols, more specifically, polyols having n hydroxyl groups where n is 2 or greater, 3 or greater, 4 or greater, 5 or greater, 6 or greater, 8 or greater, 10 or greater, 12 or greater, or 16 or greater; Monovalent or polyvalent carboxylic acids containing one or more hydroxyl groups, more specifically, glycolic acid, lactic acid, malic acid, tartaric acid, or citric acid; Sugars, more specifically trioses, tetroses, pentoses, hexoses, monosaccharides, disaccharides, trisaccharides, or oligosaccharides; Sugar alcohols, more specifically sugar alcohols containing 2 to 24 carbon atoms, in particular ethylene glycol, glycerol, erythritol, treitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, boremitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; or A topical composition according to any one of embodiments 38 to 43, comprising sugar acids, more specifically aldonic acid, urosonic acid, uronic acid, or aldalic acid; or salts thereof; or esters thereof, particularly C1-C4 alkyl esters thereof; or amides thereof. 45. C1~C 60 The topical composition according to Embodiment 44, wherein the portion has a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and particularly 120 g / mol to 1200 g / mol. 46. ​​Group b) C1~C 60 A topical composition according to any one of embodiments 38 to 45, wherein a portion or polymer portion is configured to act as a skin moisturizer. 47. C1-C of group b) 60 A topical composition according to any one of embodiments 38 to 45, wherein the partial or polymer portion is configured to act as a skin moisturizer after cleavage from the 3,4-dihydro-2H-pyran portion. 48. C1-C of group b) 60 The part or polymer part is aliphatic C 10 ~C 60Part, more specifically C 15 ~C 60 aliphatic portion, especially C 20 ~C 60 aliphatic portion, or A topical composition according to Embodiment 38, comprising an oligosiloxane or polysiloxane, particularly a poly(di-C1-C4-alkyl)siloxane. 49. C1~C 60 The topical composition according to Embodiment 48, wherein the portion has a molecular weight of 140 g / mol to 2000 g / mol, more specifically 160 g / mol to 1600 g / mol, and particularly 180 g / mol to 1200 g / mol. 50. C1~C 60 The portion is a topical composition according to Embodiment 48 or Embodiment 49, having 31 or more carbon atoms. 51. C1~C 60 The portion is saturated or unsaturated C 10 ~C 60 The aliphatic portion, more specifically C 15 ~C 60 aliphatic portion, especially C 20 ~C 60 A topical composition according to any one of embodiments 48 to 50, comprising an aliphatic moiety. 52. C atom, C1~C 60 The ratio of the heteroatoms contained in the portion to the total is about 60:1 to 5:1, more specifically about 50:1 to 10:1, and in particular about 40:1 to 20:1, and the heteroatoms are selected from nitrogen and oxygen, as described in any one of embodiments 48 to 51 of the topical composition. 53. C1~C 60 A topical composition according to any one of embodiments 48 to 52, wherein the portion is sphingosine or a derivative thereof, particularly ceramide or sphingomyelin. 54. C1~C 60 A topical composition according to any one of embodiments 48 to 53, wherein a portion is configured to act as a skin moisturizer, more specifically as an emollient, and as an evaporation inhibitor. 55. At least one of A1, A2, and A3 is configured to act as an insecticide and / or to act as an insecticide after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C 60 A topical composition according to any one of embodiments 1 to 37, which is a part of the composition. 56. The topical composition according to Embodiment 55, wherein the insecticide is an insect repellent. 57. The topical composition according to Embodiment 55, wherein the insecticide is an insecticide. 58. A topical composition according to Embodiment 56 or Embodiment 57, wherein the insecticide or insecticide acts against external parasites and / or blood-sucking insects, particularly blood-sucking insects selected from the group consisting of mosquitoes, ticks, mites, gnats, fleas, chiggers, leeches and insects. 59. The topical composition according to Embodiment 56 or Embodiment 58, wherein the insecticide is an insect repellent selected from isoprenoids, tertiary amides, and phenylpropanoids. 60. The topical composition according to Embodiment 59, wherein the insect repellent is an isoprenoid, more specifically a monoterpenoid, diterpenoid, or triperpenoid, in particular terpineol or its derivatives, monoterpenoid aldehyde or its derivatives, limonoid or its derivatives; or pyrethrin or its derivatives. 61. The topical composition according to Embodiment 60, wherein the isoprenoid is selected from citronellal, hydroxycitronellal, citronellol, citral A, citral B, or derivatives thereof; necrodan, in particular α-necrodol, or derivatives thereof; limonoid, in particular azathilactin, or derivatives thereof; or pyrethrin, in particular jasmolin, synerin, or derivatives thereof. 62. The topical composition according to Embodiment 60, wherein one of A1, A2, or A3 is selected from the part of formula (VIa) or formula (VIb). 【0468】 [ka] 63. Compounds that can covalently bond to the skin are those of formula (VII), 【0469】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L5 either does not exist, or is -C(O)-, -C(O)-O-, -C(O)-O-(CH2). 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, -S(O)2-, -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - is one of the bases selected from R 4 The topical composition according to Embodiment 60, wherein H or C1-C4 alkyl is selected. 64. Compounds that can covalently bond to the skin are compounds of formula (VIII), 【0470】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 The topical composition according to Embodiment 63, wherein is an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. 65. R 3 represents H or methyl, and R 1The topical composition according to Embodiment 63 or Embodiment 64, wherein H represents the topical composition. 66. The topical composition according to Embodiment 59, wherein the insect repellent is a phenylpropanoid, particularly eugenol or a derivative thereof. 67. The topical composition according to Embodiment 59, wherein the insect repellent comprises a tertiary amide. 68. The topical composition according to Embodiment 67, wherein the tertiary amide is selected from picaridin, N,N-di(C1-C6-alkyl)-toluamide, particularly N,N-diethyl-meth-toluamide, p-menthane-3,8-diol, ethyl 3-(N-butylacetamide)propanoate, and derivatives thereof. 69. The topical composition according to Embodiment 67, wherein the insect repellent is selected from one of the following compounds: N,N-diethyl-methatoluamide, diethylphenylacetamide, N-butylacetanilide, ethyl butylacetylaminopropionate, picaridin, N-(2-methylpiperidine-1-yl)cyclohexa-3-en-1-carboxamide, and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine or 1-[3-cyclohexen-1-ylcarbonyl]piperidine, and one of their parts / derivatives. 70. The topical composition according to Embodiment 67, wherein one of A1, A2, or A3 is a part of formula (IX). 【0471】 [ka] 71. The topical composition according to Embodiment 67, wherein one of A1, A2, or A3 is a part of formula (X). 【0472】 [ka] 72. Compounds that can covalently bond to the skin are compounds of formula (XI), 【0473】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L6 is either non-existent or -(CH2) 1~4 , -C(O)-, -C(O)-O-, -C(O)-O-(CH2) 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, -S(O)2-, -S(O)2-O-, -S(O)2-O-(CH2) 1~4 It is one of the following groups: R 4 The topical composition according to Embodiment 67, wherein H or C1-C4 alkyl is selected. 73. Compounds that can covalently bond to the skin are compounds of formula (XII), 【0474】 [ka] or its tautomers and / or pharmaceutically acceptable salts, where R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 The topical composition according to Embodiment 67, wherein is a hydrogen atom or an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with an optionally substituted substituent. 74. R 3 represents H or methyl, and R 1 The topical composition according to Embodiment 72 or Embodiment 73, wherein H represents the topical composition. 75. The topical composition according to Embodiment 57, wherein the insecticide is a topical insecticide, particularly selected from permethrin; cypermethrin; deltamethrin; ivermectin; amidine, particularly amitraz; benziocarb; malathion; carbaryl; diazinon; DDT; fenthion; fipronil; imidacloprid; nitenpyram; and propoxul. 76. C1~C 60 A topical composition according to any one of embodiments 55 to 75, wherein a portion is configured to act as an insecticide, particularly as an insect repellent. 77. C1~C 60 A topical composition according to any one of embodiments 55 to 75, wherein the portion consists of an insecticide, particularly an insect repellent, after cleavage from the 3,4-dihydro-2H-pyran portion. 78. At least one of A1, A2, and A3 is configured to act as a skin whitening agent and / or to act as a skin whitening agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 A topical composition according to any one of Embodiments 1 to 37, comprising a portion or a polymer portion. 79. The topical composition according to Embodiment 78, wherein the skin whitening agent acts by chemically or metabolically whitening the skin, particularly by providing a fading effect or reducing melanin production. 80. A topical composition according to Embodiment 78 or Embodiment 79, wherein the skin whitening agent is selected from corticosteroids, particularly clobetasol derivatives, fluocinolone derivatives, or betamethasone; vitamin A derivatives, particularly tretinoin, isotretinoin, alitretinoin, retinol, or retinal; hydroxyphenol derivatives, particularly hydroquinone; aliphatic dicarboxylic acids, particularly azelaine; α-hydroxy acids, particularly lactic acid and glycolic acid; and vitamin C. 81. Group b) C1~C 60 A topical composition according to any one of embodiments 78 to 80, wherein a portion or polymer portion is configured to act as a skin whitening agent. 82. Group b) C1~C 60A topical composition according to any one of embodiments 78 to 80, wherein the partial or polymer portion is configured as a skin whitening agent after cleavage from the 3,4-dihydro-2H-pyran portion. 83. At least one of A1, A2, and A3 is configured to act as an aromatherapy agent after being cleaved from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 A topical composition according to any one of embodiments 1 to 37, which is a part of the composition. 84. C1~C 60 The part is C1~C 60 The topical composition according to Embodiment 83, comprising a functional group configured to bond to the corresponding L1, L2, or L3 portion, or, if the corresponding L1, L2, or L3 portion is absent, to the 3,4-dihydro-2H-pyran portion and be cleaved into an aldehyde, ketone, thiol, hydroxyl, or amine. 85. The topical composition according to Embodiment 84, wherein the functional group is an imine, acetal, 1,1-diester, enol ether, ester, amide, thioester, or thioacetal. 86. C1~C 60 The topical composition according to Embodiment 84, wherein the portion has a post-cleavage molecular weight of less than 400 g / mol, more specifically less than 300 g / mol, and particularly less than 200 g / mol. 87. At least one of A1, A2, and A3 is configured to act as a pharmaceutical agent and / or to act as a pharmaceutical agent after cleavage from the 3,4-dihydro-2H-pyran moiety, C1-C of group b) 60 A topical composition according to any one of Embodiments 1 to 37, comprising a portion or a polymer portion. 88. The topical composition according to Embodiment 87, wherein the pharmaceutical is suitable for treating skin-related diseases. 89. The topical composition according to Embodiment 88, wherein skin-related diseases are selected from acneiform rash, autoinflammatory syndrome, chronic vesicular formation, mucosal conditions, skin appendage conditions, subcutaneous fat conditions, congenital anomalies, connective tissue diseases, abnormalities of skin fibers and elastic tissue, skin growth and subcutaneous growth, dermatitis, eczema, seborrheic dermatitis, pigment disorders, endocrine-related skin conditions, eosinophilic skin conditions, skin lesions, skin cancer, erythema, hereditary dermatopathy, infection-related skin conditions, lichenoid rash, lymphatic system-related skin conditions, melanocyte nevi and neoplasms, monocyte-related and macrophage-related skin conditions, mucinosis, neurocutaneous conditions, noninfectious immunodeficiency-related skin conditions, nutrition-related skin conditions, papular desquamation keratosis, palmoplantar keratoderma, pruritus, psoriasis, reactive neutrophilic skin conditions, skin conditions resulting from metabolic disorders, skin conditions resulting from physical factors, urticaria, dandruff, desquamation disorders, and vascular-related skin conditions. 90. C1~C 60 A topical composition according to any one of embodiments 87 to 89, wherein the portion is an agonist of a retinoid receptor, more specifically a retinoic acid receptor, a retinoid X receptor, and / or a RAR-related orphan receptor. 91. C1~C 60 A topical composition according to any one of embodiments 87 to 89, wherein the portion comprises a vitamin A vitamer, more specifically retinol, tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, adapalene and / or bexarotene, particularly a vitamer selected from the group consisting of retinol, retinal and / or adapalene. 92. Group b) C1~C 60 A topical composition according to any one of embodiments 87 to 92, wherein a portion or polymer portion is configured to act as a dermatological pharmaceutical. 93. Group b) C1-C 60 A topical composition according to any one of embodiments 87 to 92, wherein the partial or polymer portion is configured as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran portion. 94. Compound of formula (I), 【0475】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. Compounds of formula (I), or their tautomers and / or pharmaceutically acceptable salts, intended for medical use. 95. Compound of formula (I), 【0476】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. Compounds of formula (I), or their tautomers and / or pharmaceutically acceptable salts thereof, for use in the treatment of skin-related disorders, allergic conditions, pain, or inflammation. 96. Compound of formula (I), 【0477】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 It represents a part, At least one of A1, A2, and A3 is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety C1-C 60 It is a part, L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. For medical use, the pharmaceutical is a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, released over a period of time or days. 97. Compound of formula (I), 【0478】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as a pharmaceutical product, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. Compounds of formula (I), or their tautomers and / or pharmaceutically acceptable salts thereof, for use in the treatment of acneiform rash, autoinflammatory syndrome, chronic vesicular formation, mucosal conditions, skin appendage conditions, subcutaneous fat conditions, congenital abnormalities, connective tissue disorders, abnormalities of skin fibers and elastic tissue, skin growth and subcutaneous growth, dermatitis, eczema, seborrheic dermatitis, pigment disorders, endocrine-related skin conditions, eosinophilic skin conditions, skin lesions, skin cancer, erythema, hereditary dermatopathy, infection-related skin conditions, lichenoid rash, lymphatic system-related skin conditions, melanocyte nevi and neoplasms, monocyte-related and macrophage-related skin conditions, mucinosis, neurocutaneous conditions, non-infectious immunodeficiency-related skin conditions, nutrition-related skin conditions, papular desquamation keratosis, palmoplantar keratoderma, pruritus, psoriasis, reactive neutrophilic skin conditions, skin conditions due to metabolic disorders, skin conditions due to physical factors, urticaria, dandruff, desquamation disorders, or vascular-related skin conditions. 98. Use of any one of the topical compositions described in Embodiments 1 to 93 as a skin moisturizer, insecticide, especially insect repellent, skin whitening agent, or fragrance. 99. A method of using a topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound that can covalently bond to the skin is a compound of formula (I), 【0479】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Consistently configured to act as a skin moisturizer, insecticide, or skin whitening agent, and / or b2) After cleavage from the 3,4-dihydro-2H-pyran moiety, it is configured to act as a skin moisturizer, insecticide, skin whitening agent, or fragrance. L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position of the carbon atoms marked "a" and "b," respectively. The method comprises applying a topical composition to the skin. 100. The method according to Embodiment 99, comprising leaving a topical composition on the skin for at least 30 minutes. 101. The method according to Embodiment 100, comprising peeling the skin before applying the topical composition to the skin. 102. A method for treating a domesticated animal or livestock, the method comprising applying a topical composition to the skin and / or coat of the domesticated animal or livestock, the topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, the compound that can covalently bond to the skin being a compound of formula (I), 【0480】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L1, L2, and L3 independently represent linker groups, or are absent. A1, A2, and A3 are independent of each other. a) C1~C 30 Partial, H, hydroxyl, amino, or halogen, b) C1~C 60 Represents a part or polymer part, At least one of A1, A2, and A3 is C1-C of group b). 60 It is a part or a polymer part, b) C1~C 60 The part or polymer part is b1) Construed to act as an insecticide and / or b2) It is configured to act as an insecticide after cleavage from the 3,4-dihydro-2H-pyran moiety. A method in which L1-A1 and L2-A2 do not represent a portion containing an unsaturated CC bond or CN bond at the alpha position of the carbon atom marked "a" and "b", respectively. 103. A compound disclosed in any one of Embodiments 1 to 102. 104. Compound of formula (XIII), 【0481】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L7 is -C(O)-, -C(O)-(CH2) 1~4 -, -C(O)-O-, -C(O)-O-(CH2) 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, or -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - is a group selected from R 4 is a compound of formula (XIII), selected from H or C1-C4 alkyl, or its tautomers and / or pharmaceutically acceptable salts. 105. R 3 represents H or methyl, and R1 This is the compound described in Embodiment 104, where H is represented. 106. L7 is -C(O)-, -C(O)-O-(CH2) 1~4 -, or -C(O)-NHC(O)-C(O)-O-(CH2) 1~4 - A compound selected from Embodiment 104 or Embodiment 105. 107. Compound of formula (XIV), 【0482】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 A compound of formula (XIV), or its tautomers and / or pharmaceutically acceptable salts, where is an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. 108. R 3 represents H or methyl, and R 1 This is the compound described in Embodiment 107, where H is represented. 109. Compound of formula (XV), 【0483】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R 5 This represents H, OH, C1-C4-alkyl, NH2, N(C1-C4-alkyl)2, N-morpholino-1-yl, or piperidine-1-yl. L8 is -C(O)-, -C(O)-(CH2) 1~4 -, -C(O)-O-, -C(O)-O-(CH2) 1~4 -, -C(O)-NR 4 C(O)-, -C(O)-NR 4 C(O)-(CH2) 1~4 -, or -S(O)2-O-, -S(O)2-O-(CH2) 1~4 - is a group selected from R 4 is a compound of formula (XV), selected from H or C1-C4 alkyl, or its tautomers and / or pharmaceutically acceptable salts. 110. R 3 represents H or methyl, and R 1 This is the compound described in Embodiment 109, where H is represented. 111. L8 is -C(O)-, -C(O)-O-(CH2) 1~4 -, or -C(O)-NHC(O)-C(O)-O-(CH2) 1~4 - A compound selected from Embodiment 109 or Embodiment 110. 112. R 5 The compound according to any one of embodiments 109 to 111, wherein is H or piperidine-1-yl. 113. Compound of formula (XVI), 【0484】 [ka] or its tautomers and / or pharmaceutically acceptable salts, wherein, R 1 This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R 3 This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R 5A compound of formula (XVI), or a tautomer and / or pharmaceutically acceptable salt thereof, where is H, OH, C1-C4-alkyl, NH2, N(C1-C4-alkyl)2, N-morpholino-1-yl, or piperidine-1-yl. 114. R 3 represents H or methyl, and R 1 This is the compound described in Embodiment 113, where H is represented. 115. R 5 The compound according to Embodiment 113 or Embodiment 114, wherein H represents or piperidine-1-yl. 116. R 3 C1-C12 includes 1-14 carbon atoms, more specifically 1-12, especially 1-8; 0-12 oxygen atoms, more specifically 0-8, especially 0-6; 0-8 nitrogen atoms, more specifically 0-6, especially 0-4; 0-6 sulfur atoms, more specifically 0-4, especially 0-3; and 0-10 halogen atoms, more specifically 0-8, especially 0-6. 14 A composition or compound according to any one of embodiments 1 to 115, representing a portion of the composition or compound. 117. R 3 C 1~14 Alkyl, C 2~14 Alkenylene, C 2~14 Alkinylene, C 6~14 C containing aryl, 1 to 4 nitrogen atoms, 1 to 3 oxygen atoms and / or 1 to 2 sulfur atoms. 4~14 Represents a heteroaryl group, and any of the aforementioned groups, R 3 A composition or compound according to any one of Embodiments 1 to 116, further optionally substituted, provided that the sum of the elements listed above does not exceed the sum of the elements listed above. 118. R 3is a composition or compound according to any one of Embodiments 1 to 117, which is phenyl optionally substituted, particularly phenyl optionally substituted, particularly having 6 to 14, more particularly 6 to 12, especially 6 to 10 carbon atoms; 0 to 12, more particularly 0 to 8, especially 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, especially 0 to 6 halogen atoms. 119. R 3 is -C 1~4 alkyl, -O-C 1~4 alkyl, -S-C 1~4 alkyl, -NH-C 1~4 alkyl, -N(C 1~4 alkyl)2, -C(O)C 1~4 alkyl, -CO2C 1~4 alkyl, -O2C-C 1~4 alkyl, -C(O)NH-C 1~4 alkyl, -C(O)N(C 1~4 alkyl)2, -NH-C(O)C 1~4 alkyl, -N(C 1~4 alkyl)-C(O)C 1~4 alkyl, -SO3H, -NO2, -NH2, -OH, -SH, -COOH, -C(O)H, halogen, particularly Cl, Br or F, and -CF3, and is substituted with one or more moieties selected from the group consisting of, a composition or compound according to any one of Embodiments 116 to 118.

Claims

[Claim 1] A topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound that can covalently bond to the skin is a compound of formula (I), or a tautomer thereof and / or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 In the formula, R １ This represents a protecting group that is hydrolyzable under physiological conditions after application of hydrogen or the topical composition to the skin. L １ , L ２ and L ３ These independently represent a linker group, or are absent. A １ A ２ and A ３ They are independent of each other, a) C １ ~C ３０ moiety, H, hydroxyl, amino, or halogen, or b) C １ ~C ６０ Represents a part or polymer part, A １ A ２ and A ３ At least one of them is C of group b) １ ~C ６０ It is a part or a polymer part, b) C of group １ ~C ６０ The portion or the polymer portion is b1) Consistent with acting as a skin moisturizer, insecticide, skin whitening agent, or pharmaceutical, and / or b2) After cleavage from the 3,4-dihydro-2H-pyran moiety, it is configured to act as a skin moisturizer, insecticide, skin whitening agent, fragrance, or pharmaceutical. L １ -A １ and L ２ -A ２ This refers to a topical composition that does not represent a portion containing an unsaturated C-C bond or C-N bond at the alpha position of the carbon atoms marked "a" and "b," respectively. [Claim 2] b) C of group １ ~C ６０ The portion or the polymer portion is C １ ~C ６０ The part corresponds to L １ , L ２ Or L ３ In the portion, or the corresponding L １ , L ２ Or L ３ The topical composition according to claim 1, wherein if the portion is absent, it comprises a functional group that binds to the 3,4-dihydro-2H-pyran portion. [Claim 3] The topical composition according to claim 2, wherein the functional group is cleavable under physiological conditions after application of the topical composition to the skin. [Claim 4] The topical composition according to claim 2 or 3, wherein the functional group is hydrolyzable at the physiological pH of mammalian skin, more specifically human skin, particularly at a pH of about 5 to about 6, and / or the functional group is enzymatically cleaved under physiological conditions after application of the topical composition to the skin, particularly by enzymes present in human skin. [Claim 5] The topical composition according to any one of claims 2 to 4, wherein the functional group comprises carbon esters, particularly monoesters, 1,1-diesters, carbonates, or carbamates; ethers or thioethers, particularly acetals, hemiacetals, glycoside groups, or thioacetals; carbon amides, particularly peptides or N-Mannich bases; enols; enamines; imines; oximes; sulfate esters; sulfonic acid esters; sulfonic acid amides; phosphate esters; phosphonic acid esters; phosphate amides; or phosphonic acid amides. [Claim 6] A １ b) The C １ ~C ６０ A represents a portion or the polymer portion, ２ and A ３ They are independent of each other, C １ ~C ３０ A topical composition according to any one of claims 1 to 5, comprising a part, H, hydroxyl, amino, or halogen. [Claim 7] L １ and L ２ It exists and optionally substituted to form a five-membered ring or a six-membered ring, particularly cyclopentyl or cyclohexyl, and A １ and A ２ is -O-, -S-, -C(O)-, -CO ２ -, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, -(CH ２ ) １～４ -, - (CH ２ ) １～４ -O- and -O- (CH ２ ) １～４ - A topical composition according to any one of claims 1 to 6, wherein a group selected from a combination thereof is optionally bonded via the group. [Claim 8] The compound that can be covalently bonded to the skin is the compound of formula (II), or its tautomer and / or pharmaceutically acceptable salt. 【Chemistry 2】 In the formula, R １ , L ３ A １ , and A ３ This is as defined in any one of claims 1 to 7, (R ２ ) ｎ H and C are independent of each other. １ ~C ４ Alkyl, C １ ~C ４ Represents n parts selected from alkoxyl, hydroxyl, amino, or halogen, n is an integer selected from 1 and 2. L ４ It does not exist, or -O-, -S-, -C(O)-, -CO ２ -, -OC(O)-, -NR ４ -, -NR ４ -C(O)-, -C(O)-NR ４ -, - (CH ２ ) １～４ -, - (CH ２ ) １～４ -O-, -O-(CH ２ ) １～４ - or a base selected from a combination thereof, R ４ is H or C １ ~C ４ - A topical composition according to any one of claims 1 to 7, selected from alkyl groups. [Claim 9] The compound that can be covalently bonded to the skin is the compound of formula (III), or its tautomer and / or pharmaceutically acceptable salt. 【Transformation 3】 In the formula, R １ , L ３ A １ , and A ３ This is as defined in any one of claims 1 to 7, L ４ It does not exist, or -O-, -S-, -C(O)-, -CO ２ -, -OC(O)-, -NR ４ -, -NR ４ -C(O)-, -C(O)-NR ４ -, - (CH ２ ) １～４ -, - (CH ２ ) １～４ -O-, -O-(CH ２ ) １～４ - or a base selected from a combination thereof, R ４ is H or C １ to C ４ -alkyl, and is the topical composition according to any one of claims 1 to 8. [Claim 10] The compound that can be covalently bonded to the skin is the compound of formula (IV), or its tautomers and / or pharmaceutically acceptable salts. 【Chemistry 4】 In the formula, R １ and A １ This is as defined in any one of claims 1 to 7, (R ２ ) ｎ represents, independently of each other, n moieties selected from H, C １ - C ４ alkyl, C １ - C ４ alkoxyl, hydroxyl, amino, or halogen, and n is an integer selected from 1 and 2. L ４ It does not exist, or -O-, -S-, -C(O)-, -CO ２ -, -OC(O)-, -NR ４ -, -NR ４ -C(O)-, -C(O)-NR ４ -, - (CH ２ ) １～４ -, - (CH ２ ) １～４ -O- and -O- (CH ２ ) １～４ - is one of the following: R ３ This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R ４ is H or C １ ~C ４ - A topical composition according to any one of claims 1 to 9, selected from alkyl groups. [Claim 11] The compound that can be covalently bonded to the skin is the compound of formula (V), or its tautomer and / or pharmaceutically acceptable salt. 【Transformation 5】 In the formula, R １ and A １ This is as defined in any one of claims 1 to 7, L ４ It does not exist, or -O-, -S-, -C(O)-, -CO ２ -, -OC(O)-, -NR ４ -, -NR ４ -C(O)-, -C(O)-NR ４ -, - (CH ２ ) １～４ -, - (CH ２ ) １～４ -O- and -O- (CH ２ ) １～４ - is one of the following: R ３ This is as defined in claim 10, R ４ is H or C １ ~C ４ - A topical composition according to any one of claims 1 to 10, selected from alkyl groups. [Claim 12] Said C １ ~C ６０ The portion is configured to act as a skin moisturizer. １ ~C ６０ It is a part, Polyols, more specifically, polyols having n hydroxyl groups where n is 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, or 16 or more; Monovalent or polyvalent carboxylic acids containing one or more hydroxyl groups, more specifically, glycolic acid, lactic acid, malic acid, tartaric acid, or citric acid; Sugars, more specifically trioses, tetroses, pentoses, hexoses, monosaccharides, disaccharides, trisaccharides, or oligosaccharides; Sugar alcohols, more specifically sugar alcohols containing 2 to 24 carbon atoms, in particular ethylene glycol, glycerol, erythritol, treitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, boremitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; or Sugar acids, more specifically aldonic acid, urosonic acid, uronic acid or aldaric acid; or salts thereof; or esters thereof, especially their C １ ~C ４ - A topical composition according to any one of claims 1 to 11, comprising an alkyl ester or an amide thereof. [Claim 13] A compound of formula (VII), or its tautomers and / or pharmaceutically acceptable salts, 【Transformation 6】 In the formula, R １ This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R ３ This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L ５ It does not exist, or -C(O)-, -C(O)-O-, -C(O)-O-(CH ２ ) １～４ -, -C(O)-NR ４ C(O)-, -C(O)-NR ４ C(O)-(CH ２ ) １～４ -, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -O-(CH ２ ) １～４ - is one of the following: R ４ is H or C １ ~C ４ - A compound of formula (VII) selected from alkyl groups, or its tautomers and / or pharmaceutically acceptable salts, A compound of formula (XI), or its tautomers and / or pharmaceutically acceptable salts, 【Transformation 7】 In the formula, R １ This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R ３ This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L ６ It does not exist, or -(CH ２ ) １～４ , -C(O)-, -C(O)-O-, -C(O)-O-(CH ２ ) １～４ -, -C(O)-NR ４ C(O)-, -C(O)-NR ４ C(O)-(CH ２ ) １～４ -, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -O-(CH ２ ) １～４ It is one of the following groups, R ４ is H or C １ ~C ４ - A compound of formula (XI) selected from alkyl groups, or its tautomers and / or pharmaceutically acceptable salts, A compound of formula (XIII), or its tautomers and / or pharmaceutically acceptable salts, 【Transformation 8】 In the formula, R １ This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R ３ This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. L ７ is -C(O)-, -C(O)-(CH ２ ) １～４ -, -C(O)-O-, -C(O)-O-(CH ２ ) １～４ -, -C(O)-NR ４ C(O)-, -C(O)-NR ４ C(O)-(CH ２ ) １～４ - or -S(O) ２ -O-, -S(O) ２ -O-(CH ２ ) １～４ - is a base selected from, R ４ is H or C １ ~C ４ - A compound of formula (XIII) selected from alkyl groups, or its tautomers and / or pharmaceutically acceptable salts, A compound of formula (XV), or its tautomers and / or pharmaceutically acceptable salts, 【Chemistry 9】 In the formula, R １ This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. R ３ This represents an optionally substituted hydrocarbon moiety containing 1 to 14 carbon atoms in combination with hydrogen or an optionally substituted substituent. R ５ H, OH, C １ ~C ４ - Alkyl, NH ２ , N(C １ ~C ４ -Alkyl) ２ , represents N-morpholino-1-yl or piperidine-1-yl, L ８ is -C(O)-, -C(O)-(CH ２ ) １～４ -, -C(O)-O-, -C(O)-O-(CH ２ ) １～４ -, -C(O)-NR ４ C(O)-, -C(O)-NR ４ C(O)-(CH ２ ) １～４ -, or -S(O) ２ -O-, -S(O) ２ -O-(CH ２ ) １～４ - is a base selected from, R ４ is H or C １ ~C ４ - Compounds of formula (XV) selected from alkyl groups, or tautomers and / or pharmaceutically acceptable salts thereof. [Claim 14] A method for using a topical composition comprising a compound that can covalently bond to the skin and an excipient suitable for topical administration, wherein the compound that can covalently bond to the skin is a compound of formula (I), or a tautomer thereof and / or a pharmaceutically acceptable salt thereof, 【Chemistry 10】 In the formula, R １ This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L １ , L ２ and L ３ These either represent a linker group independently of each other, or they are absent. A １ A ２ and A ３ They are independent of each other, a) C １ ~C ３０ Partial, H, hydroxyl, amino, or halogen, b) C １ ~C ６０ Represents a part or polymer part, A １ A ２ and A ３ At least one of them is C of group b) １ ~C ６０ It is a part or a polymer part, b) C of group １ ~C ６０ The portion or the polymer portion is b1) Consistent with acting as a skin moisturizer, insecticide or skin whitening agent, and / or b2) After cleavage from the 3,4-dihydro-2H-pyran moiety, it is configured to act as a skin moisturizer, insecticide, skin whitening agent, or fragrance. L １ -A １ and L ２ -A ２ These do not represent the portions containing an unsaturated C-C bond or C-N bond at the alpha position of the carbon atoms marked "a" and "b," respectively. The method comprises applying the topical composition to the skin. [Claim 15] A compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, 【Chemistry 11】 In the formula, R １ This represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a topical composition to the skin. L １ , L ２ and L ３ These either represent a linker group independently of each other, or they are absent. A １ A ２ and A ３ They are independent of each other, a) C １ ~C ３０ Partial, H, hydroxyl, amino, or halogen, b) C １ ~C ６０ It represents a part, A １ A ２ and A ３ At least one of them is C of group b) １ ~C ６０ It is a part, b) C of group １ ~C ６０ The portion or the polymer portion is b1) Construed to act as a pharmaceutical, and / or b2) It is configured to act as a pharmaceutical after cleavage from the 3,4-dihydro-2H-pyran moiety, L １ -A １ and L ２ -A ２ These do not represent the portions containing an unsaturated C-C bond or C-N bond at the alpha position of the carbon atoms marked "a" and "b," respectively. A compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, intended for medical use.

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