Compound, method for producing the compound, and method for producing a sugar amide compound

Abstract

A novel production method of a compound having a structure in which a saccharide skeleton is introduced into an amino acid derivative. When producing a glycoprotein as the compound, solid-phase synthesis of a peptide is unnecessary, formation of a non-natural structure is unnecessary, and a production method with a low degree of limitation of applicable saccharides is provided. 【Solution means】A compound represented by the following formula (where R 1 is an acetylamino group or a hydroxyl group; R 2 , R 3 , R 4 and R 5 are an alkyl group, an aryl group or an aralkyl group; G 1 is a hydrogen atom, a methyl group, or a group represented by the general formula -CH2-OX 3 ; X 1 , X 2 and X 3 are a hydrogen atom, a monovalent group having a structure in which the anomeric hydroxyl group in a saccharide is removed, etc.). TIFF2026084686000104.tif46170

Description

[Technical Field]

[0001] The present invention relates to compounds, methods for producing compounds, and methods for producing sugar amide compounds. [Background technology]

[0002] Post-translational protein modification (sometimes referred to as "post-translational modification" in this specification) is an important factor in regulating protein activity. Recent research has revealed that a wide range of biological processes are controlled by post-translational modification, and for example, post-translational modification is being actively studied to elucidate the causes of diseases such as Alzheimer's syndrome and Parkinson's syndrome.

[0003] Among post-translational modified proteins, glycoproteins, which have a structure in which sugar chains are attached to the protein, are among the most widespread, and it is thought that more than half of cell surface proteins and secreted proteins are glycoproteins. Examples of glycoprotein types include N-type glycoproteins, which have a structure in which sugar chains are attached to the amino group (-NH2) of an asparagine (Asn) residue in the protein, and O-type glycoproteins, which have a structure in which sugar chains are attached to the hydroxyl group (-OH) of a serine (Ser) or threonine (Thr) residue in the protein. However, because these sugar chains form a wide variety of structures in living organisms, it is usually difficult to identify which sugar chain structures are biochemically important.

[0004] In response to this, many researchers have performed chemical synthesis of glycoproteins with uniform glycan structures to evaluate the effect of glycan structure on glycoprotein activity. Representative chemical synthesis methods for peptides include, for example, native chemical ligation (see Non-Patent Literature 1) and solid-phase synthesis (see Non-Patent Literature 2), and methods for synthesizing glycoproteins using these methods are known.

[0005] As a method for synthesizing a natural N-type glycoprotein, a sugar chain containing an asparagine thioacid residue, a peptide (p1) having a mercapto carbonyl group (-C(=O)-SH), and a peptide (p2) having an amino group (-NH2) are prepared. The amino group in the asparagine thioacid residue contained in the sugar chain is reacted with the mercapto carbonyl group in the peptide (p1), and the mercapto carbonyl group in the asparagine thioacid residue contained in the sugar chain is reacted with the amino group in the peptide (p2) to condense the sugar chain with the peptide (p1) and the peptide (p2), thereby synthesizing a glycoprotein (see Non-Patent Document 3).

[0006] As a method for synthesizing an unnatural glycoprotein, a method for obtaining a glycoprotein by binding an N-linked sugar chain having a mercapto group and an antibody protein via a reactive artificial linker is disclosed (see Non-Patent Document 4). By using the glycoprotein thus obtained and comparing the effects of the protein with or without a sugar chain, it may be possible to analyze the function of the sugar chain.

[0007] Naturally, glycosyltransferases exist, and a method for synthesizing glycoproteins using them is also known. For example, as a method for synthesizing a natural N-type glycoprotein, a method of excising the sugar chain in a glycoprotein and then adding another sugar chain using a glycosyltransferase is disclosed. This method is utilized for the sugar chain editing of cell surface proteins (see Non-Patent Document 5).

Prior Art Documents

Non-Patent Documents

[0008]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

[0009] However, the peptide synthesis methods disclosed in Non-Patent Documents 1 and 2 require many steps, including the protection and deprotection of functional groups that are not targeted by the reaction. As a result, the synthesis of glycoproteins is time-consuming and costly. Furthermore, it is difficult to increase the size of the peptides, and the types of glycoproteins that can be synthesized are limited. In other words, these methods have problems specific to solid-phase peptide synthesis. The method for synthesizing glycoproteins disclosed in Non-Patent Document 3 also had the same problems as described above because it involved solid-phase synthesis of peptides. The glycoproteins obtained by the method disclosed in Non-Patent Document 4 are non-natural products, which presents a problem in that it is difficult to accurately understand the function of natural glycoproteins. The method disclosed in Non-Patent Document 5 requires the preparation of an enzyme to bind the target glycan to the target site on the cell surface protein, which has the problem of limiting the types of glycans that can be applied.

[0010] Up to this point, we have described the problems in the production of glycoproteins. However, the problems with the method disclosed in Non-Patent Document 4 can also occur with low-molecular-weight compounds that have a structure in which monosaccharides or oligosaccharides are attached, rather than polysaccharides with a large number of monosaccharide bonds, and with amino acid derivatives having only one amino acid residue, rather than peptides or proteins. Therefore, there is a need for the development of new production methods, including novel methods for all compounds that have a structure in which a sugar backbone is introduced into an amino acid derivative, regardless of the number of amino acid residues.

[0011] The present invention is a novel production method for a compound having a structure in which a saccharide skeleton is introduced into an amino acid derivative. When producing a glycoprotein as the compound, solid-phase synthesis of a peptide is unnecessary, formation of a non-natural structure is unnecessary, and it is an object of the present invention to provide a production method with a low degree of limitation on applicable saccharides.

Means for Solving the Problems

[0012] To solve the above problems, the present invention adopts the following configuration. [1] The following general formula (1)

[0013]

Chemical formula

[0014] [2] The compound according to [1], wherein the saccharide is a monosaccharide, or an oligosaccharide or polysaccharide having a structure in which 2 to 15 monosaccharides are bonded. [3] The compound according to [2], wherein the monosaccharide is glucose, and the oligosaccharide has no structure in which a monosaccharide other than glucose is bonded, or has a structure in which galactose or sialic acid is bonded. [4] The above R 2 , R3 , R 4 and R 5 The compound is one of any one of the following [1] to [3], wherein each is independently an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms. [5] The R 2 and R 5 However, each is independently an alkyl group having 1 to 5 carbon atoms, or an aralkyl group having 7 to 11 carbon atoms. The aforementioned R 3 and R 4 However, each is independently an alkyl group having 1 to 5 carbon atoms, as described in [4]. [6] The following general formula (11)

[0015] [ka] (In the formula, R 1 is an acetylamino group or a hydroxyl group; G 1 This is a hydrogen atom, a methyl group, or the general formula -CH2-OX 3 It is a base represented by X 1 , X 2 and X 3 Each of these is independently a monovalent group having a structure in which a hydrogen atom, a hydroxyl group at the anomeric position in a sugar, or a monovalent group having a structure in which one or more hydrogen atoms in the sugar are replaced by substituents, and the hydroxyl group at the anomeric position in a substituted sugar, respectively. Compounds represented by the following general formula (12)

[0016] [ka] (In the formula, R 2 , R 3 , R 4 and R 5 Each of these is independently an alkyl group, an aryl group, or an aralkyl group; Q 1 (This is either a hydroxyl group or a leaving group.) By reacting a compound represented by the following general formula (1) with , the following compound is obtained

[0017] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X 1 , X 2 and G 1 (This is the same as above.) A method for producing a compound represented by [the given formula].

[0018] [7] The following general formula (1)

[0019] [ka] (In the formula, R 1 R is an acetylamino group or a hydroxyl group; 2 , R 3 , R 4 and R 5 Each of these is independently an alkyl group, an aryl group, or an aralkyl group; G 1 This is a hydrogen atom, a methyl group, or the general formula -CH2-OX 3 It is a base represented by X 1 , X 2 and X 3 Each of these is independently a monovalent group having a structure in which a hydrogen atom, a hydroxyl group at the anomeric position in a sugar, or a monovalent group having a structure in which one or more hydrogen atoms in the sugar are replaced by substituents, and the hydroxyl group at the anomeric position in a substituted sugar, respectively. By irradiating the compound represented by with light, the compound is activated, The activated product of the above compound and the following general formula (2)

[0020] [ka] (In the formula, R 9 is a hydrogen atom or an alkyl group; Z 1 and Z 2Each of these is independently a hydrogen atom; a protecting group; a monovalent group having a structure in which a hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein, provided that Z 1 and Z 2 It is not the case that both are monovalent groups; Z 3 Z is a monovalent group having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide or protein; or a monovalent group having a structure in which a carboxyl group or substituted carboxyl group has been removed from a peptide or protein; and is not a hydrogen atom. 1 or Z 2 And, Z 3 These elements may be joined to each other to form a ring. By reacting a compound represented by the following general formula (3) with , the compound represented by is obtained.

[0021] [ka] (In the formula, R 1 , X 1 , X 2 , G 1 , R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) A method for producing a sugar amide compound, which is represented by [the formula shown]. [8] A method for producing a sugar amide compound according to [7], wherein the compound represented by the general formula (1) is activated by irradiating it with light in the presence of a photocatalyst. [9] The photocatalyst is the following formula

[0022] [ka] A method for producing a sugar amide compound according to [8], wherein one or more compounds are selected from the group consisting of compounds represented by [8].

[10] The R 9 However, it is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. Said Z 3 A method for producing a sugar amide compound according to any one of [7] to [9], wherein the compound is an alkoxy group having 1 to 5 carbon atoms; an aryloxy group having 6 to 10 carbon atoms; an aralkyloxy group having 7 to 11 carbon atoms; an amino group; a substituted amino group; a monovalent group having a structure in which a hydrogen atom in an amino group or a substituted amino group has been removed from an amino acid, a substituted amino acid, a peptide or protein; or a monovalent group having a structure in which a carboxyl group or a substituted carboxyl group has been removed from a peptide or protein.

[11] The compound represented by the above general formula (2) is given by the following general formula (21)

[0023] [ka] (In the formula, R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) Dehydration reaction in a compound represented by the following general formula (22)

[0024] [ka] (In the formula, R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) A method for producing a sugar amide compound according to any one of [7] to

[10] , obtained by a hydrogen desulfurization reaction in a compound represented by [1].

[12] The aforementioned R 2 , R 3 , R 4 and R 5 A method for producing a sugar amide compound according to any one of the items [7] to

[11] , wherein each is independently an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms.

[13] A method for producing a sugar amide compound according to any one of [7] to

[12] , wherein the sugars are monosaccharides, or oligosaccharides or polysaccharides having a structure in which 2 to 15 monosaccharides are bonded together.

[14] A method for producing a sugar amide compound according to

[13] , wherein the monosaccharide is glucose, and the oligosaccharide does not have a structure to which a monosaccharide other than glucose is attached, or has a structure to which galactose or sialic acid is attached. [Effects of the Invention]

[0025] According to the present invention, a novel means and method for producing a compound having a structure in which a sugar skeleton is introduced into an amino acid derivative is provided, wherein when producing a glycoprotein as the compound, solid-phase synthesis of peptides is unnecessary, the formation of unnatural structures is unnecessary, and the applicable sugars are less limited. [Modes for carrying out the invention]

[0026] In this specification, the unit of concentration "M" means "mol / L", and "mM" means "mmol / L".

[0027] <<Compound>> A compound according to one embodiment of the present invention is given by the following general formula (1)

[0028] [ka] (In the formula, R 1 R is an acetylamino group or a hydroxyl group; 2 , R 3 , R 4 and R 5 Each of these is independently an alkyl group, an aryl group, or an aralkyl group; G 1 This is a hydrogen atom, a methyl group, or the general formula -CH2-OX 3 It is a base represented by X 1 , X 2 and X 3is, independently of each other, a hydrogen atom, a monovalent group having a structure in which the anomeric hydroxyl group in a saccharide is removed, or a monovalent group having a structure in which the anomeric hydroxyl group in a substituted saccharide in which one or more hydrogen atoms in the saccharide are substituted with a substituent is removed.) is represented by In the present specification, the compound represented by the general formula (1) may be referred to as "compound (1)". A monovalent group having a structure in which the anomeric hydroxyl group in a saccharide is removed may be referred to as a "group derived from a saccharide". A monovalent group having a structure in which the anomeric hydroxyl group in a substituted saccharide in which one or more hydrogen atoms in the saccharide are substituted with a substituent is removed may be referred to as a "group derived from a substituted saccharide".

[0029] Compound (1) is, for example, the following general formula (1 09 ) the compound represented by (compound (1 09 )) may be.

[0030]

Chemical formula

[0031] Compound (1) has, as a saccharide, a backbone of a monosaccharide or an oligosaccharide or polysaccharide having a structure in which two or more monosaccharides are bonded.

[0032] Among compound (1 09 ), G 1 is a group represented by the general formula -CH2-OX 3 , X 1 , X 2 and X 3 (In the present specification, these groups are collectively referred to as "X 1 ~X 3A derivative of glucose or N-acetylglucosamine (sometimes abbreviated as ") in which all atoms are hydrogen atoms is a derivative of glucose or N-acetylglucosamine having a structure in which the hydroxyl group at the anomeric position of glucose or N-acetylglucosamine is replaced by a group having a 1,4-dihydropyridine skeleton and represented by the following general formula (1β).

[0033] [ka] (In the formula, R 2 , R 3 , R 4 and R 5 The same applies as described above; the bond marked with an asterisk (*) is formed with respect to the carbon atom at position 1 of the monosaccharide skeleton in the general formula (1).

[0034] In this specification, unless otherwise specified, when a particular compound is assumed to have a structure in which one or more hydrogen atoms are replaced by a group other than a hydrogen atom, or a structure in which one or more hydroxyl groups are replaced by a group other than a hydroxyl group, or in other cases where a group bonded to a carbon atom is replaced by another group, a compound having such a substituted structure will be referred to as a "derivative" of the particular compound described above. In this specification, unless otherwise specified, the term "group" includes not only atomic groups formed by the bonding of multiple atoms, but also single atoms.

[0035] On the other hand, compound (1 09 ) of which G 1 The above general formula -CH2-OX 3 It is a base represented by X 1 ~X 3 If one or more of the groups are derived from the aforementioned sugars or substituted sugars, then the oligosaccharide or polysaccharide derivative has a structure in which the hydroxyl group at the anomeric position of the glucose residue or N-acetylglucosamine residue in the oligosaccharide or polysaccharide having a glucose residue or an N-acetylglucosamine residue is substituted with the group represented by the general formula (1β). The oligosaccharide or polysaccharide may be of natural origin or may be synthesized by known methods.

[0036] X 1 ~X 3 If either of the above is a group derived from a sugar or a group derived from a substituted sugar, then in compound (1), the carbon atom to which the hydroxyl group in the sugar-derived group or the group derived from a substituted sugar was attached is attached to the nitrogen atom in the amide bond.

[0037] It is presumed that compound (1), in any case, is activated by irradiation with light, causing the 1,4-dihydropyridine skeleton to be eliminated and a compound represented by the following general formula (10) having a carbamoyl radical to be produced. This reaction, in which the 1,4-dihydropyridine skeleton is eliminated and a carbamoyl radical is produced, is well known (see, for example, "Angew. Chem. Int. Ed. 2020, 59, 5248"). In other words, it is presumed that compound (1) is a sugar-derived carbamoyl radical precursor. It is then presumed that compound (10) immediately reacts with a compound having a carbon-carbon double bond (C=C) at the site of the double bond. In other words, compound (1) can introduce a sugar skeleton into the compound having the double bond, and for example, by using a peptide or protein as the compound having the double bond, a glycopeptide or glycoprotein can be produced. For example, by using compound (2), described later, as the compound having the double bond, a sugar amide compound (compound (3), described later) can be produced. And, for example, by using a peptide or protein as compound (2), a glycopeptide or glycoprotein can be produced. In this case, naturally derived peptides or proteins can be used, in which case solid-phase synthesis of the peptide is unnecessary. On the other hand, peptides or proteins synthesized by known methods such as solid-phase synthesis can also be used. Thus, by using compound (1), glycopeptides or glycoproteins can be efficiently produced in a short process without using enzymatic reactions. Furthermore, it enables the general-purpose analysis of the correlation between the structure and function of glycopeptides or glycoproteins.

[0038] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X 1 , X 2 and G 1 (This is the same as above.)

[0039] In this specification, not only in the case of compound (1), when a compound is represented by a general formula or another formula (a non-generalized formula; in this specification, sometimes simply referred to as "formula"), a symbol may be assigned to these general formulas or other formulas. In such cases, as with compound (1), a name with that symbol may be assigned to the compound.

[0040] In general formula (1), R 1 R is either an acetylamino group (-NH-C(=O)-CH3) or a hydroxyl group (-OH). 1 Regardless of which of these compounds it is, compound (1) is excellent at introducing a sugar skeleton into a compound having the double bond (for example, compound (2) described later; the same applies hereinafter).

[0041] In general formula (1), G 1 This is a hydrogen atom (-H), a methyl group (-CH3), or the general formula -CH2-OX. 3 It is a base represented by .

[0042] In general formula (1), X 1 , X 2 and X 3 Each of these is independently a monovalent group having a structure in which a hydrogen atom (-H) and a hydroxyl group at the anomeric position in a sugar (in other words, a hydroxyl group bonded to the carbon atom at position 1 in the monosaccharide skeleton; the same applies hereinafter) have been removed (i.e., a group derived from the sugar), or a monovalent group having a structure in which the hydroxyl group at the anomeric position in a substituted sugar, in which one or more hydrogen atoms in the sugar are replaced by substituents, has been removed (i.e., a group derived from the substituted sugar). X 1 ~X 3 For example, they may all be identical, all be different, or only partially identical.

[0043] In other words, in compound (1), the structure represented by the following general formula (1α) on the opposite side of the amide bond (-NH-(C=O)-) from the 1,4-dihydropyridine skeleton is a monosaccharide, or an oligosaccharide or polysaccharide having a structure in which two or more monosaccharides are bonded, in which the hydroxyl group at the anomeric position has been removed.

[0044] [ka] (In the formula, R 1 , X 1 , X 2 and G 1 The same applies as described above; the bond marked with an asterisk (*) is formed with respect to the imino group in general formula (1).

[0045] X 1 ~X 3 The sugars in this embodiment may be monosaccharides, oligosaccharides, or polysaccharides, and may be either naturally derived sugars (monosaccharides, oligosaccharides, or polysaccharides) or non-naturally derived sugars. In other words, in this embodiment, when introducing a sugar skeleton into the compound having the double bond, the applicable sugars are not particularly limited, and the degree of limitation on sugars is low. Among the aforementioned sugars, the oligosaccharides and polysaccharides may consist of only one monosaccharide or two or more monosaccharides. If they consist of two or more monosaccharides, the combination and ratio of these two or more monosaccharides can be arbitrarily selected according to the purpose. In other words, X 1 ~X 3 The polysaccharides in this context may be either simple polysaccharides (homoglycans) or complex polysaccharides (heteroglycans).

[0046] In this specification, sugars composed of 2 to 9 monosaccharides are referred to as oligosaccharides, and sugars composed of 10 or more monosaccharides are referred to as polysaccharides.

[0047] X 1 ~X 3 Among the sugars in the above, the monosaccharide may be, for example, either the D-form or the L-form, either the furanose type or the pyranose type, or either the α-type or the β-type. The monosaccharide preferably has 4 or more carbon atoms, and may be any of 4 to 7, for example. Examples of the aforementioned monosaccharides include hexoses (six-unit sugars) such as glucose, galactose, fructose, and mannose; pentoses (five-unit sugars) such as ribose, arabinose, xylose, lyxose, ribulose, and xylulose; tetroses (tetra-unit sugars) such as erythrose and threose; heptoses (seven-unit sugars) such as sedoheptulose; and sialic acid.

[0048] X 1 ~X 3 Among the aforementioned sugars, disaccharides include, for example, maltose, lactose, cellobiose, sucrose, trehalose, xylobiose, and isomaltulose (also known as palatinose). X 1 ~X 3 Among the sugars mentioned above, examples of trisaccharides include maltotriose, cerototriose, fucosyl lactose, sialyl lactose, gentianose, raffinose, and meletitose. X 1 ~X 3 Among the aforementioned sugars, examples of tetrasaccharides include stachyose, acarbose, and sialyl Lewis X.

[0049] X 1 ~X 3 Among the sugars in the above, examples of oligosaccharides include those composed of one or more selected from the group consisting of monosaccharides, disaccharides, trisaccharides, and tetrasaccharides mentioned above. X 1 ~X3 Among the sugars mentioned above, polysaccharides include, for example, starch, glycogen, cellulose, dextrin, and inulin, and also include those composed of one or more selected from the group consisting of monosaccharides, disaccharides, trisaccharides, and tetrasaccharides.

[0050] In the substituted sugars, examples of hydrogen atoms in the substituted sugars include hydrogen atoms in an amino group (-NH2), an imino group (-NH-), a hydroxyl group (-OH), and so on. Examples of substituents that substitute one or more hydrogen atoms in the sugars include acyl groups such as acetyl groups (-C(=O)-CH3).

[0051] X 1 ~X 3 If at least one of the groups is a group derived from the sugars or a group derived from a substituted sugar, then compound (1) is a derivative of an oligosaccharide or polysaccharide. Such compound (1) can react with the compound having the double bond to form a compound containing an oligosaccharide or polysaccharide structure (for example, the glycopeptide or glycoprotein), which is useful for analyzing the function of the oligosaccharide or polysaccharide structure in the compound containing the oligosaccharide or polysaccharide structure. Furthermore, X 1 ~X 3 If all of these are hydrogen atoms or groups derived from the aforementioned sugars or substituted sugars with a small number of monosaccharide bonds, then compound (1) is a derivative of a monosaccharide or oligosaccharide, and not a derivative of a polysaccharide. However, the characteristics of the reaction of compound (1) with the compound having the double bond are X 1 ~X 3 It is less susceptible to the influence of the type of compound. Therefore, such a compound (1) is useful not only because the reactant obtained using it may be useful itself, but also because it allows for the evaluation of the ability to form the sugar amide compound (e.g., the glycopeptide or glycoprotein) containing a polysaccharide structure that partially has a monosaccharide or oligosaccharide structure in compound (1).

[0052] In compound (1), X1 ~X 3 All of them are hydrogen atoms, or X 1 ~X 3 Preferably, only one of the two is a group derived from the aforementioned sugar or a group derived from a substituted sugar, and the remaining two are both hydrogen atoms. More specifically, compound (1) is, for example, the following general formula (1 01 )-A, (1 01 )-B, (1 01 )-C, or (1 01 )-D

[0053] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 and R 5 The same as above; X 11 , X 21 and X 31 This refers to a monovalent group having a structure in which the hydroxyl group at the anomeric position of a sugar is removed, or a monovalent group having a structure in which the hydroxyl group at the anomeric position of a substituted sugar, in which one or more hydrogen atoms in the sugar are replaced by substituents, is removed. It is preferable that the compound is represented by [formula].

[0054] General formula (1 01 )-A, (1 01 )-B, (1 01 )-C, or (1 01 )-D, X 11 , X 21 or X 31 X is a group derived from the aforementioned sugars or a group derived from substituted sugars, and is not a hydrogen atom. 1 , X 2 or X 3 It is the same as this. These compounds (1 01 )-A, compound (1 01 )-B, compound (1 01 )-C, or compound (1 01By using )-D, a more useful product can be obtained as a reaction product with the compound having the double bond.

[0055] Compound (1) is, for example, the following general formula (1 09 )-A, (1 09 )-B, (1 09 )-C, or (1 09 )-D

[0056] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X 11 , X 21 and X 31 (This is the same as above.) It may also be a compound represented by .

[0057] Compound (1) is, for example, the following general formula (1 02 )-A, (1 02 )-B, or (1 02 )-C

[0058] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X 11 and X 21 (This is the same as above.) It is preferable that the compound is represented by [formula]. These compounds (1 02 )-A, compound (1 02 )-B, compound (1 02 )-C, or compound (1 02 By using )-D, a more useful product can be obtained as a reaction product with the compound having the double bond.

[0059] Compound (1) is, for example, the following general formula (1 03 )-A, (1 03 )-B, or (1 03 )-C

[0060] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X 11 and X 21 (This is the same as above.) It is preferable that the compound is represented by [formula]. These compounds (1 03 )-A, compound (1 03 )-B, compound (1 03 )-C, or compound (1 03 By using )-D, a more useful product can be obtained as a reaction product with the compound having the double bond.

[0061] As described above, in order to better evaluate the ability of the sugar amide compound containing a polysaccharide structure, it is preferable that the sugars are monosaccharides, or oligosaccharides or polysaccharides having a structure in which 2 to 15 monosaccharides are linked together. Furthermore, in terms of the existence of many useful evaluation targets, it is preferable that the monosaccharide is glucose, and that the oligosaccharide does not have a structure to which monosaccharides other than glucose are attached, or has a structure to which galactose or sialic acid is attached. The polysaccharide may or may not have a structure to which monosaccharides other than glucose are attached.

[0062] In general formula (1), R 2 , R 3 , R 4 and R 5 (In this specification, these groups are collectively referred to as "R 2 ~R 5 These are sometimes abbreviated as '', and are independently an alkyl group, an aryl group, or an aralkyl group. R 2~R 5 For example, they may all be identical, all be different, or only partially identical.

[0063] R 2 ~R 5 The alkyl group in may be linear, branched, or cyclic, and may have both a linear structure (linear or branched) and a cyclic structure. If the alkyl group is cyclic, including the case where it is cyclic, the cyclic structure may be monocyclic or polycyclic. The number of carbon atoms in the alkyl group is preferably 1 to 10.

[0064] The linear or branched alkyl group preferably has 1 to 10 carbon atoms. Examples of such chain-like alkyl groups include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, n-hexyl group, 2-methylpentyl group, 3-methylpentyl group, 2,2-dimethylbutyl group, 2,3-dimethylbutyl group, n-heptyl group, 2-methylhexyl group, 3-methylhexyl group, 2,2-dimethylpentyl group, 2,3-dimethylpentyl group, 2,4-dimethylpentyl group, 3,3-dimethylpentyl group, 3-ethylpentyl group, 2,2,3-trimethylbutyl group, n-octyl group, isooctyl group, 2-ethylhexyl group, nonyl group, decyl group, and the like. The number of carbon atoms in the chain-like alkyl group is more preferably 1 to 7, even more preferably 1 to 5, and may be any of 1 to 4, 1 to 3, or 1 to 2.

[0065] The number of carbon atoms in the alkyl group having a cyclic structure, such as the cyclic alkyl group (cycloalkyl group), is preferably 3 to 10. Examples of such cyclic alkyl groups include monocyclic or polycyclic alkyl groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, norbornyl group, isobornyl group, 1-adamantyl group, 2-adamantyl group, and tricyclodecyl group. Examples of alkyl groups having both a linear and a cyclic structure include monovalent groups having a structure in which one or more hydrogen atoms (-H) in the linear or branched alkyl group are substituted with the cyclic alkyl group. The number of carbon atoms in the alkyl group having the cyclic structure is more preferably 3 to 7, and may be, for example, 3 to 5 and 5 to 7.

[0066] R 2 ~R 5 The aryl group in the above-mentioned compound may be monocyclic or polycyclic. The number of carbon atoms in the aryl group is preferably 6 to 15.

[0067] Examples of the aryl group include phenyl group, 1-naphthyl group, 2-naphthyl group, 4-methylphenyl group (p-tolyl group), 3-methylphenyl group (m-tolyl group), 2-methylphenyl group (o-tolyl group), 2,3-dimethylphenyl group (2,3-xylyl group), 2,4-dimethylphenyl group (2,4-xylyl group), 2,5-dimethylphenyl group (2,5-xylyl group), 2,6-dimethylphenyl group (2,6-xylyl group), 3,4-dimethylphenyl group (3,4-xylyl group), 3,5-dimethylphenyl group (3,5-xylyl group), and 2,4,6-trimethylphenyl group (mesityl group). The aforementioned aryl group may also include a monovalent group having a structure in which one or more hydrogen atoms in the aforementioned aryl group are further substituted with the alkyl group or aryl group.

[0068] The number of carbon atoms in the aryl group is more preferably 6 to 12, and may be, for example, 6 to 10 and 6 to 8.

[0069] R 2 ~R 5 The aralkyl group in this context is a monovalent group having a structure in which one hydrogen atom in the alkyl group is substituted with the aryl group. For example, the aromatic ring in the aralkyl group may be monocyclic or polycyclic. The number of carbon atoms in the aralkyl group is preferably 7 to 16.

[0070] The number of carbon atoms in the aralkyl group is more preferably 7 to 13, and may be, for example, 7 to 11 and 7 to 9. Preferred aralkyl groups include, for example, benzyl groups (phenylmethyl groups) and phenethyl groups (2-phenylethyl groups).

[0071] R 2 ~R 5 Each of these is preferably an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms. Among them, R 2 ~R 5 Each of these is more preferably independently a chain-like alkyl group having 1 to 7 carbon atoms, a cyclic alkyl group having 3 to 7 carbon atoms, an aryl group having 6 to 12 carbon atoms, or an aralkyl group having 7 to 13 carbon atoms. For example, each may independently be a chain-like alkyl group having 1 to 5 carbon atoms, a cyclic alkyl group having 5 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, or an aralkyl group having 7 to 11 carbon atoms.

[0072] In compound (1), R 2 and R 5 If they are identical to each other, or R 3 and R 4 It is preferable that they are the same as each other, R 2 and R 5 They are identical to each other, and R 3 and R 4It is more preferable that they are identical to each other. Such a compound (1) not only excels in its ability to introduce a sugar skeleton into the compound having the double bond, but is also easier to produce.

[0073] In compound (1), R 2 and R 5 However, each is independently an alkyl group or an aralkyl group, R 3 and R 4 However, each is more preferably an alkyl group, R 2 and R 5 However, each is independently an alkyl group having 1 to 5 carbon atoms, or an aralkyl group having 7 to 11 carbon atoms, R 3 and R 4 However, it is particularly preferable that each of them be an alkyl group having 1 to 5 carbon atoms. Such a compound (1) is particularly excellent in its ability to introduce a sugar skeleton into the compound having the double bond, and is also easier to produce.

[0074] In other words, compound (1) is given by the following general formula (1)-1

[0075] [ka] (In the formula, R 1 The same as above; R 21 , R 31 , R 41 and R 51 Each of these is independently an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms; X 1 , X 2 and G 1 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0076] R in general formula (1)-1 21 , R 31 , R 41 and R 51In this, the alkyl group having 1 to 10 carbon atoms, the aryl group having 6 to 15 carbon atoms, and the aralkyl group having 7 to 16 carbon atoms are, respectively, R 2 ~R 5 Among the alkyl, aryl, and aralkyl groups in the above, those with a limited number of carbon atoms are those described above.

[0077] Compound (1) is, for example, the following general formula (1 09 )-1

[0078] [ka] (In the formula, R 1 , R 21 , R 31 , R 41 , R 51 , X 1 , X 2 and G 1 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0079] Compound (1)-1 is, for example, the following general formula (1 01 )-1A, (1 01 )-1B, (1 01 )-1C, or (1 01 )-1D

[0080] [ka] (In the formula, R 1 , R 21 , R 31 , R 41 , R 51 , X 11 , X 21 and X 31 (This is the same as above.) It is preferable that the compound is represented by [formula]. These compounds (1 01 )-1A, compound (1 01 )-1B, compound (1 01 )-1C, and compound (1 01)-1D can be manufactured even more easily, and by using these, a more useful product can be obtained as a reaction product with the compound having the double bond.

[0081] Compound (1)-1 is, for example, the following general formula (1 09 )-1A, (1 09 )-1B, (1 09 )-1C, or (1 09 )-1D

[0082] [ka] (In the formula, R 1 , R 21 , R 31 , R 41 , R 51 , X 11 , X 21 and X 31 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0083] Compound (1)-1 is, for example, the following general formula (1 02 )-1A, (1 02 )-1B, or (1 02 )-1C

[0084] [ka] (In the formula, R 1 , R 21 , R 31 , R 41 , R 51 , X 11 and X 21 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0085] Compound (1)-1 is, for example, the following general formula (1 03 )-1A, (1 03 )-1B, or (1 03 )-1C

[0086] [ka] (In the formula, R 1 , R 21 , R 31 , R 41 , R 51 , X 11 and X 21 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0087] Compound (1) is given by the following general formula (1)-2

[0088] [ka] (In the formula, R 1 The same as above; R 22 and R 52 Each of these is independently an alkyl group having 1 to 5 carbon atoms, or an aralkyl group having 7 to 11 carbon atoms; R 32 and R 42 Each of these is an alkyl group having 1 to 5 carbon atoms; X 1 , X 2 and G 1 (This is the same as above.) It is particularly preferable that the compound is represented by [formula]. Compound (1)-2 is particularly excellent in its ability to introduce a sugar skeleton into the compound having the double bond, and is also easier to produce.

[0089] R in general formula (1)-2 22 ~R 52 In this context, alkyl groups with 1 to 5 carbon atoms are R 2 ~R 5 Among the alkyl groups in the above, those with a further limited number of carbon atoms are those described above. R in general formula (1)-2 22 and R 52 In this, the aralkyl group with 7 to 11 carbon atoms is R 2 ~R 5 Among the aralkyl groups in the above, those with a further limited number of carbon atoms are those described above.

[0090] Compound (1) is, for example, the following general formula (1 09 )-2

[0091] [ka] (In the formula, R 1 , R 22 , R 32 , R 42 , R 52 , X 1 , X 2 and G 1 (This is the same as above.) It is particularly preferable that the compound be represented by [formula].

[0092] Compound (1)-2 is, for example, the following general formula (1 01 )-2A, (1 01 )-2B, (1 01 )-2C, or (1 01 )-2D

[0093] [ka] (In the formula, R 1 , R 22 , R 32 , R 42 , R 52 , X 11 , X 21 and X 31 (This is the same as above.) It is preferable that the compound is represented by [formula]. These compounds (1 01 )-2A, compound (1 01 )-2B, compound (1 01 )-2C, and compound (1 01 )-2D can be produced particularly easily, and by using these, a more useful product can be obtained as a reaction product with the compound having the double bond.

[0094] Compound (1)-2 is, for example, the following general formula (1 09 )-2A, (1 09 )-2B, (109 )-2C, or (1 09 )-2D

[0095] [ka] (In the formula, R 1 , R 22 , R 32 , R 42 , R 52 , X 11 , X 21 and X 31 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0096] Compound (1)-2 is, for example, the following general formula (1 02 )-2A, (1 02 )-2B, or (1 02 )-2C

[0097] [ka] (In the formula, R 1 , R 22 , R 32 , R 42 , R 52 , X 11 and X 21 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0098] Compound (1)-2 is, for example, the following general formula (1 03 )-2A, (1 03 )-2B, or (1 03 )-2C

[0099] [ka] (In the formula, R 1 , R 22 , R 32 , R 42 , R 52 , X 11 and X 21 (This is the same as above.) It is preferable that the compound is represented by [formula].

[0100] <<Method for producing compounds>> Compound (1) is given by the following general formula (11)

[0101] [ka] (In the formula, R 1 is an acetylamino group or a hydroxyl group; G 1 This is a hydrogen atom, a methyl group, or the general formula -CH2-OX 3 It is a base represented by X 1 , X 2 and X 3 Each of these is independently a monovalent group having a structure in which a hydrogen atom, a hydroxyl group at the anomeric position in a sugar, or a monovalent group having a structure in which one or more hydrogen atoms in the sugar are replaced by substituents, and the hydroxyl group at the anomeric position in a substituted sugar, respectively. Compounds represented by the following general formula (12)

[0102] [ka] (In the formula, R 2 , R 3 , R 4 and R 5 Each of these is independently an alkyl group, an aryl group, or an aralkyl group; Q 1 (This is either a hydroxyl group or a leaving group.) It can be obtained by reacting a compound represented by with .

[0103] In other words, compound (1) can be produced by reacting compound (11) and compound (12) by a known amidation reaction.

[0104] R in general formula (11) 1 , X 1 , X 2 and G 1 These are R in general formula (1), respectively. 1 , X 1, X 2 and G 1 It is the same as this.

[0105] R in general formula (12) 2 , R 3 , R 4 and R 5 These are R in general formula (1), respectively. 2 , R 3 , R 4 and R 5 It is the same as this. In general formula (12), Q 1 This is a hydroxyl group or a leaving group. Q 1 The leaving group in the above may be a known one. Examples of the leaving group include halogen atoms such as chlorine (-Cl), bromine (-Br), and iodine (-I).

[0106] Of compound (1), compound (1 09 ) is given by the following general formula (11 09 )

[0107] [ka] (In the formula, R 1 , G 1 , X 1 and X 2 (This is the same as above.) Compounds represented by (compound (11 09 )) and the following general formula (12)

[0108] [ka] (In the formula, R 2 , R 3 , R 4 , R 5 and Q 1 (This is the same as above.) It can be obtained by reacting a compound represented by with .

[0109] The amount of compound (12) used is preferably 0.5 to 9.5 times the molar amount of compound (11), for example, it may be 0.5 to 4 times the molar amount and 4 to 9.5 times the molar amount, or 0.5 to 2 times the molar amount, 0.5 to 1.7 times the molar amount and 0.5 to 1.4 times the molar amount, or 0.59 to 2 times the molar amount and 0.71 to 2 times the molar amount, or 0.59 to 1.7 times the molar amount and 0.71 to 1.4 times the molar amount. If the amount of compound (12) used is above the lower limit, the amount of compound (1) produced will be greater. If the amount of compound (12) used is below the upper limit, the overuse of compound (12) will be suppressed.

[0110] Q 1 If is a hydroxyl group and compound (12) is a carboxylic acid, compound (1) can be obtained, for example, by reacting compound (11) and compound (12) using a condensing agent. Q 1 If is a hydroxyl group and compound (12) is a carboxylic acid, compound (1) can be obtained, for example, by activating compound (12) using an additive and the activated ester method, or by forming an acid anhydride using an acid halide and then reacting it with compound (11). When using the aforementioned additives or acid halides, a base may also be used.

[0111] The condensing agent, additive, and acid halide used in the reaction between compound (11) and compound (12) may be one or more, and if there are two or more, their combination and ratio can be arbitrarily selected according to the purpose.

[0112] Examples of the condensing agent include carbodiimide-based condensing agents such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl), N,N'-dicyclohexylcarbodiimide (DCC), and N,N'-diisopropylcarbodiimide (DIC); Carbonyldiimidazole-based condensing agents such as 1,1'-carbonyldiimidazole (CDI) and 1,1'-carbonyldi(1,2,4-triazole) (CDI); Triazine-based coupling agents such as 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholinium chloride (DMT-MM); Phosphonium-based condensing agents such as 1H-benzotriazol-1-yl-1-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1H-benzotriazol-1-yl-1-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP); Examples of uronium-based condensing agents include {{[(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy}-4-morpholinomethylene}dimethylammonium hexafluorophosphate (COMU), O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).

[0113] When the aforementioned condensing agent is used, the amount of condensing agent used is preferably 1 to 13 times the molar amount of compound (12), for example, it may be 1 to 7 times the molar amount, 1 to 5 times the molar amount, or 2 to 3.5 times the molar amount. If the amount of condensing agent used is above the lower limit, the amount of compound (1) produced will be greater. If the amount of condensing agent used is below the upper limit, excessive use of the condensing agent will be suppressed.

[0114] Examples of the aforementioned additives include 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), N-hydroxysuccinimide (HOSu), N,N'-disuccinimidyl carbonate (DSC), 4-nitrophenol (ONp), pentafluorophenol (OPfp), and isobutyl chloroformate.

[0115] When using the aforementioned additive or acid halide, the amount of the additive or acid halide used is preferably 0.67 to 1.5 times the molar amount of compound (12), and may be, for example, 0.83 to 1.2 times the molar amount. If the amount of the additive or acid halide used is above the lower limit, the amount of compound (1) produced will be greater. If the amount of the additive or acid halide used is below the upper limit, the excessive use of the additive or acid halide will be suppressed.

[0116] Examples of the aforementioned bases include N-methylmorpholine and N,N-diisopropylethylamine. The amount of base used is preferably 1.5 to 3 times the molar amount of the additive or acid halide used, and may be, for example, 1.8 to 2.7 times the molar amount. The effect of using the base is enhanced when the amount of base used is above the lower limit. Excessive use of the base is suppressed when the amount of base used is below the upper limit.

[0117] The reaction between compound (11) and compound (12) is preferably carried out in the presence of a solvent. Doing so improves the reaction rate between compound (11) and compound (12). The solvent used in the reaction between compound (11) and compound (12) may be one type or two or more types, and if there are two or more types, their combination and ratio can be arbitrarily selected according to the purpose.

[0118] In this specification, unless otherwise specified, the term "solvent" encompasses both a component that is liquid at room temperature for dissolving a solute and a component that is liquid at room temperature for dispersing a dispersed phase.

[0119] In this specification, "room temperature" means a temperature that is neither cooled nor heated, i.e., a normal temperature, such as 15-25°C.

[0120] The solvent is preferably capable of dissolving either or both of compound (11) and compound (12), and preferably does not react with either compound (11) or compound (12). Examples of solvents include water and organic solvents.

[0121] Examples of the aforementioned organic solvents include halogenated aliphatic hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; Amides such as 1,3-dimethyl-2-imidazolidinone (DMI), N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), and N-methyl-2-pyrrolidone (NMP); Aromatic hydrocarbons such as toluene, o-xylene, m-xylene, and p-xylene; Aliphatic hydrocarbons such as hexane; Halogenated aromatic hydrocarbons such as chlorobenzene, 1,2-dichlorobenzene (o-dichlorobenzene), 1,3-dichlorobenzene (m-dichlorobenzene), and 1,4-dichlorobenzene (p-dichlorobenzene); Examples include tetrahydrofuran (THF), ethers such as 1,4-dioxane (cyclic ethers), and others.

[0122] When using two or more solvents in combination, it is preferable to use, for example, a mixed solvent of pyridine and water. In a mixed solvent of pyridine and water, the volume ratio of pyridine to water is preferably 1 / 1 to 7 / 1, for example, it may be 3 / 1 to 7 / 1, 4 / 1 to 7 / 1, 1 / 1 to 5 / 1, 1 / 1 to 4 / 1, or 3 / 1 to 5 / 1. Having the volume ratio within this range enhances the effects obtained by using pyridine and water together.

[0123] When using the aforementioned solvent, the amount of solvent used is preferably such that the concentration of compound (11) in the reaction solution is 0.001 to 1 M, more preferably 0.005 to 0.5 M, and may be, for example, 0.005 to 0.01 M or 0.01 to 0.2 M. A solvent usage amount greater than or equal to the lower limit allows for a more pronounced solvent effect. A solvent usage amount less than or equal to the upper limit prevents excessive solvent use.

[0124] During the reaction between compound (11) and compound (12), other components not belonging to compound (11), compound (12), the condensing agent, the additive, the acid halide, the base, or the solvent may be used, or they may not be used.

[0125] The reaction temperature when compound (11) and compound (12) are reacted is preferably -3 to 35°C, and may be any of -3 to 5°C, 5 to 15°C, 15 to 35°C, or 15 to 25°C, or the reaction may be carried out at room temperature or other normal temperatures.

[0126] The time for reacting compound (11) and compound (12) (reaction time) is not particularly limited as long as the reaction proceeds well, but is preferably 10 to 60 hours, and may be, for example, 15 to 50 hours.

[0127] Compound (11) can be obtained, for example, by known methods, from the following general formula (13)

[0128] [ka] (In the formula, R 1 , X 1 , X 2 and G 1 (This is the same as above.) It can be obtained by reacting the compound represented by with ammonium carbamate (see, for example, "Russ. Chem. Bull. 2004, 53, 709"). However, the method for producing compound (11) is not limited thereto.

[0129] Of the compounds (12), Q 1 When is a hydroxyl group, the compound represented by the following general formula (12)-1 can be obtained, for example, by reacting the compound represented by the following general formula (14)-1, the compound represented by the following general formula (14)-2, and the compound represented by the following formula (15) (glyoxylic acid) by known methods (see, for example, "Org. Lett. 2024, 26, 660-665"). Of the compounds (12), Q 1 is the leaving group Q 11 In this case, the compound represented by the following general formula (12)-2 can be obtained by converting the "-OH" bonded to the carbonyl group (-C(=O)-) in compound (12)-1 into a leaving group using a known method.

[0130] [ka] (In the formula, R 2 , R 3 , R 4 and R 5 This is the same as above; Q 11 (This is a leaving group.)

[0131] R 2 and R 5 They are identical and R 3 and R 4 When producing compound (12)-1 or compound (12)-2 which are identical, it is sufficient to use the same compound (14)-1 and compound (14)-2.

[0132] In the above manufacturing method, after the reaction between compound (11) and compound (12), compound (1) can be extracted by post-treatment of the reaction solution as necessary using known methods. That is, post-treatment operations such as filtration, washing, extraction, pH adjustment, dehydration, and concentration can be performed individually or in combination of two or more as appropriate, and compound (1) can be extracted by concentration, crystallization, reprecipitation, distillation, column chromatography, recycled preparative gel permeation chromatography, etc. Furthermore, the extracted compound (1) may be purified by performing crystallization, reprecipitation, distillation, column chromatography, recycled preparative gel permeation chromatography, extraction, stirring and washing of crystals with a solvent, one or more times as necessary, individually or in combination of two or more. Alternatively, after the completion of the reaction, compound (1) may be used for the intended purpose without extraction, after post-treatment of the reaction solution as necessary. For example, compound (1) may be subjected to the following intended reaction without extraction.

[0133] The structure of compound (1) can be confirmed by known methods such as nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and infrared spectroscopy (IR).

[0134] <<Method of using the compound (Method for producing sugar amide compounds)>> As explained above, compound (1) is presumed to be activated by light irradiation to produce compound (10), which is a sugar-derived carbamoyl radical precursor. Furthermore, through reaction with the compound having a double bond, a compound is formed in which a sugar skeleton is introduced into the compound having a double bond. A method for producing a compound into which a sugar skeleton has been introduced, that is, a method for producing a sugar amide compound according to one embodiment of the present invention, is as follows: General formula (1)

[0135] [ka] (In the formula, R 1 R is an acetylamino group or a hydroxyl group; 2 , R 3 , R4 and R 5 Each of these is independently an alkyl group, an aryl group, or an aralkyl group; G 1 This is a hydrogen atom, a methyl group, or the general formula -CH2-OX 3 It is a base represented by X 1 , X 2 and X 3 Each of these is independently a monovalent group having a structure in which a hydrogen atom, a hydroxyl group at the anomeric position in a sugar, or a monovalent group having a structure in which one or more hydrogen atoms in the sugar are replaced by substituents, and the hydroxyl group at the anomeric position in a substituted sugar, respectively. By irradiating a compound represented by (i.e., compound (1)) with light, the compound is activated, The activated product of the above compound and the following general formula (2)

[0136] [ka] (In the formula, R 9 is a hydrogen atom or an alkyl group; Z 1 and Z 2 Each of these is independently a hydrogen atom; a protecting group; a monovalent group having a structure in which a hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein, provided that Z 1 and Z 2 It is not the case that both are monovalent groups; Z 3 Z is a monovalent group having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide or protein; or a monovalent group having a structure in which a carboxyl group or substituted carboxyl group has been removed from a peptide or protein; and is not a hydrogen atom. 1 or Z 2 And, Z 3 The two may bond to each other to form a ring. By reacting a compound represented by ) with the two, the following general formula (3) is obtained.

[0137] [ka] (In the formula, R 1 , X 1 , X 2 , G 1 , R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) A method for producing a sugar amide compound is given, which yields a sugar amide compound represented by [formula]. The sugar amide compound (compound (3)) is a compound obtained by modifying the compound having a double bond by introducing a sugar skeleton into the compound having a double bond.

[0138] The method for producing the sugar amide compound of this embodiment is, for example, the following general formula (1 09 )

[0139] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , G 1 , X 1 and X 2 (This is the same as above.) By irradiating the compound represented by with light, the compound is activated, The activated product of the above compound and the following general formula (2)

[0140] [ka] (In the formula, R 9 is a hydrogen atom or an alkyl group; Z 1 and Z 2Each of these is independently a hydrogen atom; a protecting group; a monovalent group having a structure in which a hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein, provided that Z 1 and Z 2 It is not the case that both are monovalent groups; Z 3 Z is a monovalent group having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide or protein; or a monovalent group having a structure in which a carboxyl group or substituted carboxyl group has been removed from a peptide or protein; and is not a hydrogen atom. 1 or Z 2 And, Z 3 These elements may be joined to each other to form a ring. By reacting a compound represented by the following general formula (3 09 )

[0141] [ka] (In the formula, R 1 , X 1 , X 2 , G 1 , R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) This may also be a method for producing sugar amide compounds, which yields a sugar amide compound represented by [the formula shown].

[0142] Compound (2) is the reactant for the activated compound (1). In other words, the sugar amide compound (compound (3)) is a compound obtained by modifying compound (2) by introducing the sugar skeleton from compound (1) into compound (2). On the other hand, compound (2) is an amino acid derivative having one or two or more amino acid residues.

[0143] In general formula (2), R 9 is a hydrogen atom or an alkyl group. R 9 The alkyl group in is R 2 ~R 5 Examples include those similar to the alkyl group in the above example. R 9 The number of carbon atoms in the alkyl group is preferably 1 to 10. R 9 The number of carbon atoms in the chain-like alkyl group is preferably 1 to 10, more preferably 1 to 7, and even more preferably 1 to 5, for example, it may be any of 1 to 4, 1 to 3, and 1 to 2. R 9 The number of carbon atoms in the alkyl group having a cyclic structure, such as a cyclic alkyl group (cycloalkyl group), is preferably 3 to 10, more preferably 3 to 7, and may be, for example, 3 to 5 and 5 to 7.

[0144] In terms of having many useful compounds (2), R 9 It is particularly preferable that the element is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms.

[0145] In general formula (2), Z 1 and Z 2 Each of these is independently a hydrogen atom; a protecting group; a monovalent group having a structure in which a hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein. Z 1 and Z 2 They may be the same as each other, or they may be different.

[0146] Z 1 and Z 2 Examples of the protecting group in this context include those known as protecting groups for amino groups (-NH2). More specifically, examples of the protecting groups include groups that can be deprotected under acidic conditions, such as the tert-butoxycarbonyl group (Boc group); groups that can be deprotected under basic conditions, such as the 9-fluorenylmethyloxycarbonyl group (Fmoc group); and groups that can be deprotected under acidic or basic conditions, such as the acyl group (e.g., the acetyl group).

[0147] Z 1 and Z 2 In this context, the substituted amino group to be removed from the peptide or protein is a monovalent group having a structure in which one or two hydrogen atoms in the amino group are substituted with substituents, and its type is not particularly limited. For example, the substituted amino group is Z, which will be described later. 3 It may be the same as the substituted amino group in [the given expression]. Z 1 and Z 2 In the peptide or protein, the amino group or substituted amino group to be removed may be located at the terminal or non-terminal end of the chain structure.

[0148] Z 1 or Z 2 However, in the case of a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein (which may be referred to as "monovalent group (i)" in this specification), in compound (2), the carbon atom to which the amino group or substituted amino group in the monovalent group was considered to be attached is Z 1 and Z 2 It is bonded to the nitrogen atom to which it is bonded.

[0149] Z 1 and Z 2 In this embodiment, the hydroxyl group (-OH) that is to be removed from the amino acid, substituted amino acid, peptide, or protein is the hydroxyl group in the carboxyl group (-C(=O)-OH). That is, in this embodiment, the carboxyl group is considered to have a structure in which a hydroxyl group is bonded to a carbon atom in the carbonyl group (-C(=O)-). The carboxyl group from which the hydroxyl group is removed may be located at the terminal or non-terminal end of the chain structure in the peptide or protein. Examples of the substituted amino acids include compounds in which one or more hydrogen atoms in an amino acid are replaced by a group other than a hydrogen atom. Examples of the hydrogen atoms to be substituted include hydrogen atoms in an amino group, a substituted amino group, or a hydroxyl group. The substituted amino group here is the same as the substituted amino group described above, for example, Z described later. 3 It may be the same as the substituted amino group in [the given expression].

[0150] Z 1 or Z 2 However, in the case of a monovalent group having a structure in which a hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein (which may be referred to as "monovalent group (ii)" in this specification), in compound (2), the carbon atom in the carbonyl group to which the hydroxyl group in the monovalent group was considered to be attached is Z 1 and Z 2 It is bonded to the nitrogen atom to which it is bonded.

[0151] Z 1 and Z 2 The acyl group in the above is, for example, R 2 ~R 5 Examples of monovalent groups include those having an alkyl group, aryl group, or aralkyl group bonded to a carbon atom in the carbonyl group. The number of carbon atoms in the acyl group is preferably 2 to 17. Of the aforementioned acyl groups, the number of carbon atoms in the group corresponding to an alkylcarbonyl group such as an acetyl group (Ac, -C(=O)-CH3) is preferably 2 to 11. Of the aforementioned acyl groups, the number of carbon atoms in the group corresponding to an arylcarbonyl group such as a benzoyl group (-C(=O)-C6H5) is preferably 7 to 16. Of the aforementioned acyl groups, the group corresponding to the aralkylcarbonyl group preferably has 8 to 17 carbon atoms. The acyl group is more preferably an acetyl group (Ac, -C(=O)-CH3).

[0152] In general formula (2), Z 1 and Z 2 If either of them is a monovalent group (monovalent group (i)) having a structure from which an amino group or a substituted amino group has been removed from a peptide or protein, then the other is a hydrogen atom or a protecting group, Z 1 and Z 2 Neither of them can be the aforementioned monovalent base (monovalent base (i) or monovalent base (ii)). Similarly, in general formula (2), Z 1 and Z 2 If either of them is a monovalent group (monovalent group (ii)) having a structure in which the hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein, then the other is a hydrogen atom or a protecting group, Z 1 and Z 2 Neither of them can be the aforementioned monovalent base (monovalent base (i) or monovalent base (ii)).

[0153] In general formula (2), Z 3 This refers to an alkoxy group; an aryloxy group; an aralkyloxy group; an amino group; a substituted amino group; a monovalent group having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which a carboxyl group (-C(=O)-OH) or a substituted carboxyl group has been removed from a peptide or protein.

[0154] Z 3 The alkoxy group in is R 2 ~R 5 Examples include monovalent groups having a structure in which the alkyl group is bonded to an oxygen atom.

[0155] That is, Z 3The alkoxy group in may be linear, branched, or cyclic, and may have both a linear structure (linear or branched) and a cyclic structure. In the case where the alkoxy group is cyclic, and in the case where it has a cyclic structure, the cyclic structure may be monocyclic or polycyclic. The number of carbon atoms in the alkoxy group is preferably 1 to 10.

[0156] The number of carbon atoms in the linear or branched alkoxy group is preferably 1 to 10. Examples of such chain-like alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, 1-methylbutyloxy, n-hexyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 2,2-dimethylbutyloxy, and 2,3-dimethylbutyloxy. Examples include methylbutyloxy group, n-heptyloxy group, 2-methylhexyloxy group, 3-methylhexyloxy group, 2,2-dimethylpentyloxy group, 2,3-dimethylpentyloxy group, 2,4-dimethylpentyloxy group, 3,3-dimethylpentyloxy group, 3-ethylpentyloxy group, 2,2,3-trimethylbutyloxy group, n-octyloxy group, isooctyloxy group, 2-ethylhexyloxy group, nonyloxy group, decyloxy group, etc. The number of carbon atoms in the chain-like alkoxy group is more preferably 1 to 7, even more preferably 1 to 5, and may be any of 1 to 4, 1 to 3, or 1 to 2.

[0157] The number of carbon atoms in the cyclic alkoxy group, such as the cyclic alkoxy group, is preferably 3 to 10. Examples of such cyclic alkoxy groups include monocyclic or polycyclic alkoxy groups such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, cyclononyloxy, cyclodecyloxy, norbornyloxy, isobornyloxy, 1-adamantyloxy, 2-adamantyloxy, and tricyclodecyloxy. As an alkoxy group having both a chain-like structure and a cyclic structure, one or more hydrogen atoms in the above-mentioned linear or branched alkoxy group are R 2 ~R 5 Examples include monovalent groups having a structure substituted with a cyclic alkyl group. The number of carbon atoms in the alkoxy group having the cyclic structure is more preferably 3 to 7, and may be, for example, 3 to 5 and 5 to 7.

[0158] Z 3 The aryloxy group in is R 2 ~R 5 Examples include monovalent groups having a structure in which the aryl group is bonded to an oxygen atom.

[0159] That is, Z 3 The aryloxy group in the above-mentioned part may be monocyclic or polycyclic. The number of carbon atoms in the aryloxy group is preferably 6 to 15.

[0160] Examples of the aryloxy group include phenoxy group, 1-naphthyloxy group, 2-naphthyloxy group, 4-methylphenoxy group (p-tolyloxy group), 3-methylphenoxy group (m-tolyloxy group), 2-methylphenoxy group (o-tolyloxy group), 2,3-dimethylphenoxy group (2,3-xylyloxy group), 2,4-dimethylphenoxy group (2,4-xylyloxy group), 2,5-dimethylphenoxy group (2,5-xylyloxy group), 2,6-dimethylphenoxy group (2,6-xylyloxy group), 3,4-dimethylphenoxy group (3,4-xylyloxy group), 3,5-dimethylphenoxy group (3,5-xylyloxy group), and 2,4,6-trimethylphenoxy group (mesityloxy group). The aryloxy group is defined as having one or more hydrogen atoms in the aforementioned aryloxy group, further comprising R 2 ~R 5 Examples include monovalent groups having a structure substituted with the alkyl or aryl group mentioned above.

[0161] The number of carbon atoms in the aryloxy group is more preferably 6 to 12, and may be, for example, 6 to 10 and 6 to 8.

[0162] Z 3 The aralkyloxy group in the above is R 2 ~R 5 Examples include monovalent groups having a structure in which the aralkyl group is bonded to an oxygen atom. For example, the aromatic ring in the aralkyloxy group may be monocyclic or polycyclic. The number of carbon atoms in the aralkyloxy group is preferably 7 to 16, more preferably 7 to 13, and may be, for example, 7 to 11 and 7 to 9. Preferred aralkyloxy groups include, for example, benzyloxy group (phenylmethoxy group, -O-CH2C6H5) and phenethyloxy group (2-phenylethoxy group, -O-CH2CH2C6H5).

[0163] Z3 The substituted amino group in this context is a monovalent group having a structure in which one or two hydrogen atoms in the amino group are substituted with substituents. If a substituted amino group has a structure in which two hydrogen atoms in the amino group are substituted with substituents, these two substituents may be the same or different. Examples of substituents in the substituted amino group include the aforementioned Z 1 and Z 2 Examples include protecting groups similar to those in the above; alkyl groups which may have substituents; aryl groups which may have substituents; aralkyl groups which may have substituents, etc.

[0164] The substituted amino group (Z 3 The substituents in ) are the alkyl group, aryl group, and aralkyl group, respectively, R 2 ~R 5 Examples include the same alkyl groups, aryl groups, and aralkyl groups as described above.

[0165] The substituted amino group (Z 3 The substituents in ) the alkyl group, aryl group, and aralkyl group may each have substituents, for example, one or more hydrogen atoms in the alkyl group, aryl group, and aralkyl group may be substituted with a group other than a hydrogen atom. Examples of groups other than the hydrogen atom include hydroxyl groups, halogen atoms such as chlorine, bromine, and iodine atoms. The number of hydrogen atoms substituted in the alkyl, aryl, and aralkyl groups is not particularly limited, but is preferably 1 to 3, and more preferably 1 or 2. When the number of substitutions is 2 or more, these two or more substituents may all be the same, all be different, or only some may be the same.

[0166] Z 3In this context, the substituted carboxyl group to be removed from the peptide or protein is a monovalent group having a structure in which a hydrogen atom in the carboxyl group is replaced by a substituent, and its type is not particularly limited. Examples of substituents in the substituted carboxyl group include R 2 ~R 5 Examples include alkyl groups, aryl groups, and aralkyl groups, similar to those in the context of alkyl groups, aryl groups, and aralkyl groups. Z 3 In the peptide or protein, the carboxyl group or substituted carboxyl group to be removed may be located at the terminal or non-terminal end of the chain structure.

[0167] Z 3 However, in the case of a monovalent group having a structure from which a carboxyl group or a substituted carboxyl group has been removed from a peptide or protein, in compound (2), the carbon atoms to which the carboxyl group or substituted carboxyl group in the monovalent group could be considered to be bonded are bonded to the carbon atoms in the carbonyl group.

[0168] Z 3 In the above, the substituted amino group from which a hydrogen atom is removed in an amino acid, substituted amino acid, peptide, or protein is the Z 3 This is similar to a substituted amino group. Z 3 In the peptide or protein, the amino group or substituted amino group from which the hydrogen atom is removed may be located at the terminal or non-terminal end of its chain structure.

[0169] Z 3 However, in the case of a monovalent group having a structure in which an amino group or a hydrogen atom in a substituted amino group has been removed from an amino acid, substituted amino acid, peptide, or protein, in compound (2), the nitrogen atom in the amino group or substituted amino group, which can be considered to have been bonded to the hydrogen atom in the monovalent group, is bonded to the carbon atom in the carbonyl group.

[0170] In terms of having many useful compounds (2), Z 3 Preferably, the group is an alkoxy group having 1 to 5 carbon atoms; an aryloxy group having 6 to 10 carbon atoms; an aralkyloxy group having 7 to 11 carbon atoms; an amino group; a substituted amino group; a monovalent group having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which a carboxyl group or substituted carboxyl group has been removed from a peptide or protein.

[0171] In compound (2), Z is not a hydrogen atom. 1 And, Z 3 These two components may bond to each other, forming a ring with the -N(-)-C(=)-C(=O)- group to which they are bonded. In compound (2), Z is not a hydrogen atom. 2 And, Z 3 These two components may bond to each other, forming a ring with the -N(-)-C(=)-C(=O)- group to which they are bonded. In other words, compound (2) may be a cyclic compound.

[0172] Z 1 and Z 3 When they are bonded and form a ring, Z 1 and Z 3 The positions of their bonding are not particularly limited, Z 2 and Z 3 When they are bonded and form a ring, Z 2 and Z 3 The positions of their joints are not particularly limited.

[0173] Z 1 and Z 3 The ring formed by the bonding of Z 2 and Z 3 The rings formed by the bonding of these elements may be monocyclic or polycyclic.

[0174] Z 1 and Z 3 The ring formed by the bonding of Z 2 and Z3 Preferably, the rings formed by the bonding of these elements are rings that can be considered to have been formed by the formation of amide bonds.

[0175] Z 1 and Z 3 The ring formed by bonding, and Z 2 and Z 3 Preferably, the rings formed by the bonding are all cyclic peptides. Many of the sugar amide compounds (compound (3)) obtained using such compound (2) have higher utility.

[0176] In compound (2), R 9 and Z 3 It is preferable that all of these are the preferred types mentioned above. An example of such a compound (2) is R 9 However, it is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, Z 3 However, examples include alkoxy groups having 1 to 5 carbon atoms; aryloxy groups having 6 to 10 carbon atoms; aralkyloxy groups having 7 to 11 carbon atoms; amino groups; substituted amino groups; monovalent groups having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide, or protein; or monovalent groups having a structure in which a carboxyl group or substituted carboxyl group has been removed from a peptide or protein. However, this is only one example of preferred compounds (2).

[0177] Compound (2) is, for example, the following general formula (21)

[0178] [ka] (In the formula, R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) Dehydration reaction in a compound represented by the following general formula (22)

[0179] [ka] (In the formula, R 9 , Z 1 , Z 2 and Z 3 (This is the same as above.) It is obtained by a hydrogen desulfurization reaction in the compound represented by .

[0180] The dehydration reaction in compound (21) and the hydrogen desulfurization reaction in compound (22) can both be carried out by known methods, and the conditions for dehydration or hydrogen desulfurization may be adjusted depending on the type of compound (21) or compound (22).

[0181] Z 1 or Z 2 However, a monovalent group having a structure in which a hydroxyl group in a carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein, Z 3 However, compound (2) in the case of a monovalent group having a structure from which an amino group or a hydrogen atom in a substituted amino group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure from which a carboxyl group or a substituted carboxyl group has been removed from a peptide or protein, is given by the following general formula (2α)

[0182] [ka] (In the formula, R 9 The same as above; Z 01 is a hydrogen atom or a protecting group; the bond marked with the sign * is Z in general formula (2) above. 2 Bonds formed with respect to the corresponding group; the bond denoted by ** is Z in the general formula (2). 3 (It is formed for the corresponding group.) It is a peptide or protein having a group represented by . Furthermore, the aforementioned Z 01 The following general formula (2α)-1 when is a hydrogen atom

[0183] [ka] (In the formula, R 9 The same as above; the combination with the sign * is Z in the general formula (2) above. 2 Bonds formed with respect to the corresponding group; the bond denoted by ** is Z in the general formula (2). 3 (It is formed for the corresponding group.) The group represented by is a dehydroalanine (Dha) residue, or a substituted dehydroalanine residue having a structure in which one hydrogen atom bonded to a carbon atom in the dehydroalanine residue is replaced by the alkyl group. In other words, in this case, compound (2) is a peptide or protein having a dehydroalanine residue or the substituted dehydroalanine residue. Furthermore, dehydroalanine residues are known to be produced by the dehydration reaction of serine (Ser) residues or the desulfurization reaction of cysteine ​​(Cys) residues, as shown in the following formula. 9 It is known that substituted dehydroalanine residues, when the residue is a methyl group, are produced by the dehydration reaction of threonine (Thr) residues. For example, the dehydration reaction of serine residues can be carried out using serine dehydrogenase (see, for example, the non-patent document "ACS Chem. Biol. 2009, 4, 379-385."), but is not limited to this. For example, the desulfurization reaction of cysteine ​​residues can be carried out using O-mesitylenesulfonylhydroxylamine (see, for example, the non-patent document "J. Am. Chem. Soc. 2008, 130, 5052-5053."), but is not limited to this.

[0184] [ka]

[0185] Compound (2) is obtained by reacting a peptide or protein having a dehydroalanine residue, represented by the following general formula (2)-1A, with the activated product of compound (1) (presumably compound (10)), to obtain a glycoamide compound (compound (3)), which is a glycopeptide or glycoprotein represented by the following general formula (3)-3A. On the other hand, compound (2) is represented by the following general formula (2)-1B, R 9 By reacting a peptide or protein having a substituted dehydroalanine residue (where the residue is a methyl group) with compound (10), which is an activated product of compound (1), a glycopeptide or glycoprotein represented by the following general formula (3)-3B is obtained as a sugar amide compound (compound (3)).

[0186] [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X 1 , X 2 and G 1 This is the same as above; Z 02 This refers to a monovalent group having a structure in which a hydroxyl group in a carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein; Z 03 (This refers to a monovalent group having a structure in which an amino group or a hydrogen atom in a substituted amino group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which a carboxyl group or a substituted carboxyl group has been removed from a peptide or protein.)

[0187] In other words, in this embodiment, compound (2)-1A, obtained by dehydrating a serine residue or hydrogen-desulfurizing a cysteine ​​residue using a naturally derived peptide or protein having a serine residue, is reacted with the activated product to obtain compound (3)-3A, which is a glycopeptide or glycoprotein, without forming an asparagine (Asn) residue or any unnatural structure. In this case, the glycoprotein is an N-type glycoprotein. Since no enzymatic reaction is used in this case, the size of the peptide and protein is arbitrary, and their molecular weight is not particularly limited. On the other hand, compound (2)-1B, obtained by dehydrating a threonine residue using a naturally derived peptide or protein containing a threonine residue, is reacted with the activator to obtain compound (3)-3B, which is a glycopeptide or glycoprotein, without forming any unnatural structures, while forming the aforementioned substituted asparagine residue having a structure in which a hydrogen atom is replaced by a methyl group. In this case, the glycoprotein is also an N-type glycoprotein. In this case as well, since no enzymatic reaction is used, the size of the peptide and protein is arbitrary, and their molecular weight is not particularly limited. In this way, by combining compounds (1) and (2) within a specific range, a compound (3) can be obtained in which the overall structure is composed of naturally derived materials.

[0188] Up to this point, we have described the case of obtaining glycopeptides or glycoproteins using naturally derived peptides or proteins. However, regardless of whether they contain serine, cysteine, or threonine residues, artificial peptides or proteins obtained through biochemical processing, such as those obtained through enzymatic reactions or genetic modification, can also be used. In this case, the glycopeptides or glycoproteins obtained are the same as those obtained using naturally derived peptides or proteins, except that they contain artificial peptides or proteins.

[0189] In contrast, Z 1and Z 2 is a hydrogen atom or a protecting group, Z 3 If the compound (1) is an alkoxy group, an aryloxy group, an aralkyloxy group, an amino group, or a substituted amino group, then compound (2) is an amino acid derivative, not a peptide or protein. However, such compound (2) can react with various nucleophiles, and the products are unnatural amino acids or their derivatives. Unnatural peptides obtained using these unnatural amino acids or their derivatives are expected to have various useful functions. In other words, such compound (2) is useful as a raw material for producing peptides as high-performance materials. Furthermore, such compound (2) is also useful in that it allows for the evaluation of the reactivity of compound (1) with compound (2).

[0190] The compound (2) reacted with the activated compound (1) may be just one type or two or more types. If there are two or more types, their combination and ratio can be arbitrarily selected according to the purpose.

[0191] When compound (1) reacts with the activator, the amount of compound (2) used is preferably 0.01 to 4 times the molar amount of compound (1), more preferably 0.01 to 3 times the molar amount, and may also be 0.01 to 2 times the molar amount. For example, it may be 0.01 to 0.1 times, 0.1 to 0.5 times, 0.5 to 1 time, 1 to 1.5 times, 1.5 to 2 times, and 2 to 3 times the molar amount. If the amount of compound (2) used is above the lower limit, the amount of compound (3) produced will be greater. If the amount of compound (2) used is below the upper limit, the overuse of compound (2) will be suppressed.

[0192] To activate compound (1), the light irradiated onto compound (1) is preferably visible light, and more preferably light with a wavelength of 350 to 650 nm (visible light). By irradiating with such light, compound (1) can be activated more easily.

[0193] It is preferable to irradiate compound (1) with light in the presence of either a solvent, a photocatalyst, or both. The solvent and photocatalyst used when irradiating compound (1) with light may be one type each, or two or more types each. If two or more types are used, their combination and ratio can be arbitrarily selected according to the purpose.

[0194] The irradiation time of compound (1) with light is not particularly limited, as long as compound (1) is sufficiently activated. For example, the irradiation time may be 4 to 36 hours, 8 to 24 hours, or 12 to 20 hours. The longer the irradiation time, the more activated compound (1) becomes, and the shorter the irradiation time, the more excessive light irradiation is suppressed.

[0195] The irradiation of compound (1) with light can be carried out using a lamp with an output of 30-50W, but this is just one example.

[0196] When compound (1) is activated by irradiating it with light in the presence of a solvent, compound (1) is activated with greater uniformity.

[0197] Examples of the solvent include water and organic solvents. Examples of the aforementioned organic solvents include ethers (cyclic ethers) such as tetrahydrofuran (THF) and 1,4-dioxane; Nitriles such as acetonitrile; Amides such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), N-methyl-2-pyrrolidone (NMP), and 1,3-dimethyl-2-imidazolidinone (DMI); Esters such as ethyl acetate; Halidean aliphatic hydrocarbons (halogenated hydrocarbons) such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; Ketones such as acetone and methyl ethyl ketone; Aromatic hydrocarbons (hydrocarbons) such as toluene, o-xylene, m-xylene, and p-xylene; Aliphatic hydrocarbons (hydrocarbons) such as hexane; Examples include halogenated aromatic hydrocarbons (halogenated hydrocarbons) such as chlorobenzene, 1,2-dichlorobenzene (o-dichlorobenzene), 1,3-dichlorobenzene (m-dichlorobenzene), and 1,4-dichlorobenzene (p-dichlorobenzene).

[0198] When using two or more solvents in combination, it is preferable to use, for example, a mixed solvent of an organic solvent and water. In a mixed solvent of organic solvent and water, the volume ratio of organic solvent to water is preferably 8 / 2 to 2 / 8, and may be, for example, 7 / 3 to 3 / 7 or 4 / 6 to 6 / 4. Having this volume ratio within this range enhances the effects obtained by using both organic solvent and water.

[0199] When using the aforementioned solvent, the amount of solvent used is preferably such that the concentration of compound (1) in the reaction solution is 0.001 to 1 M. For example, it may be an amount that results in a concentration of 0.001 to 0.01 M, an amount that results in a concentration of 0.005 to 0.5 M, or an amount that results in a concentration of 0.01 to 0.2 M. The effect of using the solvent is more pronounced when the amount of solvent used is above the lower limit. Excessive use of the solvent is suppressed when the amount of solvent used is below the upper limit.

[0200] When compound (1) is activated by irradiating it with light in the presence of a photocatalyst, compound (1) is activated more smoothly.

[0201] The aforementioned photocatalyst is preferably a photo-oxidation-reduction catalyst. Examples of the photo-oxidation-reduction catalyst include those represented by any of the following formulas.

[0202] [ka]

[0203] More specifically, the aforementioned photo-oxidation-reduction catalyst is, for example, 1,2,3,5-tetrakis(carbazole-9-yl)-4,6-dicyanobenzene (also known as 4CzIPN); 2,4,6-Tris(diphenylamino)-5-fluoroisodilonitrile (also known as 3DPAFIPN); Tris(2-phenylpyridinato)iridium(III) (also known as Ir(ppy)3); (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridinyl)phenyl]iridium(III) hexafluorophosphate (also known as Ir(ppy)2(dtbbpy)PF6); [4,4'-bis(1,1-dimethyl)-2,2'-bipyridine-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate (also known as Ir[dF(CF3)ppy]2(dtbbpy)PF6); [5,5'-bis(trifluoromethyl)-2,2'-bipyridine-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate (also known as [Ir(dFCF3ppy)2-(5,5'-dCF3bpy)]PF6); Tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate (also known as Ru(ppy)3); 9-(2,6-dimethylphenyl)-2-ethoxy-6-methoxy-10-methylacridinium tetrafluoroborate (also known as Acr + -diOR); 9-Mesityl-10-methylacridinium perchlorate; Examples include benzophenothiazine, tetrabromofluorescein, and perixanthenoxanthene (also known as PXX).

[0204] The amount of photocatalyst used when irradiating compound (1) with light is preferably 0.5 to 10 mol%, more preferably 1 to 7 mol%, and even more preferably 1.5 to 4 mol%, relative to the amount of compound (1) used. When the amount of photocatalyst used is above the lower limit, the effect obtained by using the photocatalyst is enhanced. When the amount of photocatalyst used is below the upper limit, excessive use of the photocatalyst is suppressed.

[0205] The aforementioned photocatalyst exhibits higher catalytic activity, as shown by the following formula.

[0206] [ka] It is preferable that the compound is selected from the group consisting of compounds represented by [formula], one or more of which are selected from the group consisting of compounds represented by [formula].

[0207] During the reaction between the activated compound (1) and compound (2), for example, the activated compound (1) may be formed first, and then compound (2) may be added to the reaction solution containing the activated compound. However, in this embodiment, it is preferable to activate compound (1) by irradiation with light in the presence of compound (2). In this case, as soon as the activated product is generated from compound (1), the activated product becomes capable of reacting with compound (2), and in this way, the activated product and compound (2) react rapidly, side reactions are suppressed, and the amount of compound (3) produced increases.

[0208] When using the aforementioned photocatalyst, the timing and method of mixing the photocatalyst with other raw materials or reactants are not particularly limited, but it is preferable to add the photocatalyst to compound (1). In particular, in this embodiment, it is preferable to add a photocatalyst to a mixture of compound (1) and compound (2). In this case, as soon as the activated product is generated from compound (1), compound (1) is activated in a state where the activated product can react with compound (2). As a result, the activated product and compound (2) react more rapidly, side reactions are further suppressed, and the amount of compound (3) produced increases even further.

[0209] When using the aforementioned photocatalyst, it is preferable to mix the photocatalyst solution or dispersion with other raw materials or reactants. This ensures that the photocatalyst is dispersed with high uniformity in the reaction solution, thereby enhancing the effects obtained from using the photocatalyst. Examples of solvents used in this case include those described earlier.

[0210] In the aforementioned solution or dispersion of the photocatalyst, the concentration of the photocatalyst is not particularly limited, but is preferably 0.3 to 10 mM, more preferably 0.6 to 6 mM, and even more preferably 0.9 to 3 mM. A concentration of the photocatalyst above the lower limit suppresses excessive solvent use and avoids excessive use of the photocatalyst solution or dispersion. A concentration of the photocatalyst below the upper limit results in higher uniformity of the photocatalyst in the solution or dispersion.

[0211] The temperature of the reaction solution (reaction temperature) when activating compound (1) and reacting the activated compound (1) with compound (2) can be adjusted as appropriate to ensure that the desired reaction proceeds smoothly. For example, the temperature (reaction temperature) is preferably 15 to 40°C, and may be any of 15 to 35°C, 15 to 30°C, or 15 to 25°C, or even room temperature. If the temperature is above the lower limit, the desired reaction will proceed more smoothly. If the temperature is below the upper limit, side reactions will be suppressed, and the amount of compound (3) produced will be greater.

[0212] During the activation of compound (1), and during the reaction between the activated product of compound (1) and compound (2), other components that do not fall under any of the following categories—compound (1), compound (2), solvent, or photocatalyst—may be used, or may not be used. The aforementioned other components may consist of only one type or two or more types, and if there are two or more types, their combination and ratio can be arbitrarily selected according to the purpose.

[0213] The aforementioned other components can be arbitrarily selected depending on the purpose and are not particularly limited. For example, if compound (2) is a peptide or protein, it is preferable to carry out the activation of compound (1) and the reaction between the activated product of compound (1) and compound (2) in a buffer solution. In this case, the other components may include components that exhibit buffering properties.

[0214] If the other component is not a component that exhibits buffering properties, then, during the activation of compound (1) and during the reaction between the activated product of compound (1) and compound (2), the ratio of the amount of the other component used (parts by mass) to the total amount of the components used (parts by mass) ([Amount of other component used (parts by mass)] / [Total amount of components used (parts by mass)] × 100) is preferably 10% by mass or less, for example, 5% by mass or less, 3% by mass or less, or 1% by mass or less. By keeping the ratio below the upper limit, the sugar amide compound can be obtained more efficiently in a simplified process. On the other hand, the aforementioned ratio is 0% by mass or more.

[0215] Here, "total amount of components used" refers to the total amount of compound (1), compound (2), solvent, photocatalyst, and the other components used. Furthermore, when calculating the above proportions, if the solvent, the photocatalyst, or any of the other components is not used, the amount of that component used shall be set to 0 parts by mass. These also apply when the other components mentioned below are components that exhibit the buffering properties.

[0216] If the other component is a component that exhibits buffering properties, the ratio of the amount (parts by mass) of the other component to the total amount (parts by mass) of the components used during the activation of compound (1) and during the reaction between the activated product of compound (1) and compound (2) is preferably 50% by mass or less, for example, 40% by mass or less, 20% by mass or less, and 10% by mass or less. By keeping the ratio below the upper limit, the sugar amide compound can be obtained more efficiently in a simplified process. On the other hand, the aforementioned ratio is 0% by mass or more.

[0217] After the reaction between the activated compound (1) and compound (2), the reaction solution can be post-treated as necessary in the same manner as when compound (1) was produced, and the sugar amide compound (compound (3)) can be isolated. The isolated sugar amide compound may be further purified as necessary in the same manner as when compound (1) was produced. Alternatively, after the reaction is complete, the reaction solution can be post-treated as necessary, and the sugar amide compound can be used for the intended purpose without being isolated. For example, the sugar amide compound can be used for the next intended reaction without being isolated.

[0218] The structure of sugar amide compounds can be confirmed by known methods such as nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and infrared spectroscopy (IR). [Examples]

[0219] The present invention will be described in more detail below with reference to specific examples. However, the present invention is not limited in any way to the examples shown below.

[0220] The main raw materials and reagents used in each example are listed below, specifically those that are commercially available. Glucose: Manufactured by Tokyo Chemical Industry Co., Ltd. N-acetyl-D-glucosamine: Manufactured by Tokyo Chemical Industry Co., Ltd. D-Lactose: Manufactured by Tokyo Chemical Industry Co., Ltd. D-Maltose Monohydrate: Manufactured by Tokyo Chemical Industry Co., Ltd. Maltopentaose: Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. 3'-Sialyl lactose sodium salt: Manufactured by Tokyo Chemical Industry Co., Ltd. Dithialyl octasaccharide: Manufactured by Tokyo Chemical Industry Co., Ltd. D-galactose: Manufactured by Tokyo Chemical Industry Co., Ltd. D-Mannose: Manufactured by Tokyo Chemical Industry Co., Ltd. D-Xylose: Manufactured by Tokyo Chemical Industry Co., Ltd. L-rhamnose monohydrate: Manufactured by Tokyo Chemical Industry Co., Ltd. Ammonium carbamate: Manufactured by Tokyo Chemical Industry Co., Ltd. N,N-Diisopropylethylamine: Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. 3,5-Bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101): Manufactured by Tokyo Chemical Industry Co., Ltd. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl: manufactured by Watanabe Chemical Industry Co., Ltd.) N,N'-Dicyclohexylcarbodiimide (DCC): Manufactured by Tokyo Chemical Industry Co., Ltd. N,N'-Diisopropylcarbodiimide (DIC): Manufactured by Tokyo Chemical Industry Co., Ltd. N-methylmorpholine (NMM): Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Isobutyl chloroformate: Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Glyoxylic acid aqueous solution (50% by mass (9M) aqueous solution): Manufactured by Tokyo Chemical Industry Co., Ltd. 4CzIPN: Manufactured by Angene International 3DPAFIPN: Manufactured by Angene International Ir(ppy)3: Manufactured by Tokyo Chemical Industry Co., Ltd. Ir(ppy)3(dtbbpy)PF6: Manufactured by Tokyo Chemical Industry Co., Ltd. Ir[dF(CF3)ppy]2(dtbbpy)PF6:BLD Manufactured by Pharmatech Ltd. Acr + -diOR: Manufactured by Tokyo Chemical Industry Co., Ltd. Benzophenothiazine: Manufactured by Tokyo Chemical Industry Co., Ltd. Tetrabromofluorescein: Manufactured by Tokyo Chemical Industry Co., Ltd. 28% aqueous ammonia (conc. NH4OH(aq)): Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Ammonium bicarbonate: Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.

[0221] [Manufacturing Example 1] <<Production of benzyl 3-aminocrotonate>> 3-aminocrotonic acid benzyl, represented by the following formula, was prepared using the method described in the reference "Green Chem. 2005, 7, 771-774.". The obtained 3-aminocrotonic acid benzyl 1The 1H NMR data is described in the reference "J. Med. Chem. 2013, 56, 2975-2990." 1 The results matched the 1H NMR data.

[0222] [ka]

[0223] [Manufacturing Example 2] <<Preparation of Compound (11)-101 (Glucosylamine, β-D-Glucopyranosylamine)>> A mixture of glucose (10.0 g, 55.5 mmol) and ammonium carbamate (8.67 g, 111 mmol) was mixed with methanol (280 mL) and stirred at 40°C for 24 hours. Then, ammonium carbamate (8.67 g, 111 mmol) was added to the resulting reaction mixture and stirred at 40°C for 25 hours. Finally, ammonium carbamate (4.33 g, 55.5 mmol) was added to the resulting reaction mixture and stirred at 40°C for 52 hours. Next, the reaction mixture was cooled to 0°C, and the precipitate was filtered. Water (20 mL), methanol (600 mL), and N,N-diisopropylethylamine (4.0 mL) were added to the filtrate, and the resulting mixture was concentrated under reduced pressure at a temperature of 30°C and a pressure of 12 kPa (120 mbar) until the volume was reduced to several mL. 2-propanol (200 mL) was added to the concentrate, and the solvent was removed by reducing the pressure to obtain the target compound (11)-101 as a colorless solid (yield 9.47 g, yield 95%). The spectral data of the obtained compound (11)-101 was consistent with the spectral data of the same compound described in the literature "Eur. J. Med. Chem. 2016, 112, 130-144."

[0224] [ka]

[0225] [Manufacturing Example 3] <<Preparation of Compound (11)-102(N-((2R,3R,4R,5S,6R)-2-amino-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)acetamide)>> A mixture of N-acetyl-D-glucosamine (450 mg, 2.03 mmol) and ammonium carbamate (638 mg, 8.18 mmol) was mixed with methanol (10 mL) and stirred at 40°C for 27 hours. Then, ammonium carbamate (159 mg, 2.04 mmol) was added to the resulting reaction mixture, and the mixture was stirred at 40°C for 22 hours. Next, the reaction mixture was cooled to 0°C, and the precipitate was filtered. To the resulting filtrate, water (1.0 mL), methanol (20 mL), and N,N-diisopropylethylamine (0.30 mL) were added, and the resulting mixture was concentrated under reduced pressure at 30°C and 12 kPa (120 mbar) until the volume was reduced to several mL. 2-propanol was added to the concentrate, and the solvent was removed by reduced pressure concentration to obtain the target compound (11)-102 as a colorless solid (yield 254 mg, yield 57%). The spectral data of the obtained compound (11)-102 matched the spectral data of the same compound described in the literature "Angew. Chem. Int. Ed. 2016, 55, 10363-10367."

[0226] [ka]

[0227] [Manufacturing Example 4] <<Preparation of Compound (11)-103 (Lactosylamine)>> A mixture of D-lactose (731 mg, 2.03 mmol) and ammonium carbamate (636 mg, 8.08 mmol) was mixed with methanol (10 mL) and stirred at 40°C for 27 hours. Then, ammonium carbamate (159 mg, 2.04 mmol) was added to the resulting reaction mixture, and the mixture was stirred at 40°C for 50 hours. Next, the reaction mixture was cooled to 0°C, and the precipitate was filtered. Water (1.6 mL), methanol (33 mL), and N,N-diisopropylethylamine (0.50 mL) were added to the filtrate, and the resulting mixture was concentrated under reduced pressure at 30°C and 12 kPa (120 mbar) until it reached a volume of several mL. 2-propanol was added to the concentrate, and the solvent was removed by reduced pressure concentration to obtain the target compound (11)-103 as a colorless solid (yield 510 mg, yield 74%). The spectral data of the obtained compound (11)-103 matched the spectral data of the same compound described in the literature "J. Am. Chem. Soc. 2014, 136, 8011-8017."

[0228] [ka]

[0229] [Manufacturing Example 5] <<Production of Compound (12)>> <Preparation of compound (12)-102 (3,5-bis(benzyloxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid)> Benzyl 3-aminocrotonate (2.01 g, 4.77 mmol) was dissolved in glacial acetic acid (2.8 mL), the resulting solution was cooled to 0°C, and the aforementioned aqueous glyoxylic acid solution (0.65 mL, 5.85 mmol as glyoxylic acid) was slowly added dropwise to it. After the dropwise addition was complete, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 15 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed by vacuum distillation, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 100 / 0~95 / 5 (volume ratio)) and recycled preparative gel permeation chromatography (GPC) (mobile phase: chloroform). Based on the above, the target compound (12)-102 was obtained (yield 75.5 mg, yield 3.1%).

[0230] The obtained compound is compound (12)-102. 1 1H NMR, 13 This was confirmed by 13C NMR and high-resolution electrospray ionization mass spectrometry (HRMS(ESI)). The analytical data obtained at this time are shown below. 1 H NMR (600 MHz, CDCl3)δ(ppm): 7.38-7.30 (m, 10H), 5.22 (s, 4H), 4.70 (s, 1H), 2.24 (d, J = 5.4 Hz, 6H), 2.01 (s, 6H). 13 C NMR (151 MHz, CDCl3)δ(ppm): 168.5, 135.8, 128.6, 128.2, 128.1, 116.3, 97.4, 66.9, 41.0, 19.5. HRMS (ESI): calculated for C 24 H 23 NO6Na ([M + Na] + ): 444.1423, found: 444.1418.

[0231] [ka]

[0232] [Manufacturing Example 6] <<Production of Compound (2)-101 (Dehydroalanine Derivative)>> The compound represented by formula (2)-101 below was prepared using the method described in the reference "ACS Catal. 2019, 9, 1558-1563." The obtained compound (2)-101 1 The 1H NMR data is described in the aforementioned document. 1 The results matched the 1H NMR data.

[0233] [ka]

[0234] [Manufacturing Example 7] <<Preparation of Compound (2)-102 (Dehydroalanine Derivative)>> The compound represented by formula (2)-102 below was prepared using the method described in the reference "J. Org. Chem. 2003, 68, 10098.". The obtained compound (2)-102 1 The 1H NMR data is described in the aforementioned document. 1 The results matched the 1H NMR data.

[0235] [ka]

[0236] [Manufacturing Example 8] <<Preparation of Compound (2)-103 (Dehydroalanine Derivative)>> The compound represented by formula (2)-103 below was prepared using the method described in the literature "Macromol. Rapid Commun., 2019, 40, 1800857.". The obtained compound (2)-103 1 The 1H NMR data is described in the aforementioned document. 1 The results matched the 1H NMR data.

[0237] [ka]

[0238] [Example 1] <<Production of Compound (1)>> <Preparation of Compound (1)-101 (Diethyl 2,6-dimethyl-4-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)carbamoyl)-1,4-dihydropyridine-3,5-dicarboxylate)> Glucosylamine (compound (11)-101, 1.20 g, 6.71 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 100 mL). The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 1.99 g, 6.70 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 3.86 g, 20.2 mmol) were added thereto. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 85 / 15~78 / 22 (volume ratio)) and flash ODS column chromatography (mobile phase: water / methanol = 58 / 42~34 / 66 (volume ratio)). Here, "ODS column chromatography" refers to column chromatography using a packing material obtained by chemically bonding octadecylsilyl (ODS) groups to a silica gel support. This is the same throughout the process. Based on the above, the target compound (1)-101 was obtained as a pale yellow solid (yield 1.81 g, yield 59%).

[0239] The obtained compound is compound (1)-101. 1 1H NMR, 13 This was confirmed by 13C NMR and high-resolution electrospray ionization mass spectrometry (HRMS(ESI)). The analytical data obtained at this time are shown below. 11H NMR (600 MHz, CD3OD) δ (ppm): 4.79 (d, J = 9.1 Hz, 1H), 4.61 (s, 1H), 4.27 - 4.18 (m, 4H), 3.82 (dd, J = 12.0, 2.0 Hz, 1H), 3.64 (dd, J = 12.0, 5.0 Hz, 1H), 3.38 (t, J = 8.8 Hz, 1H), 3.32 - 3.28 (m, 2H), 3.22 (t, J = 9.1 Hz, 1H), 2.31 (s, 3H), 2.31 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 176.1, 168.2, 168.2, 148.2, 147.9, 97.3, 96.9, 80.1, 78.4, 77.6, 72.9, 70.0, 61.4, 60.0, 60.0, 41.4, 17.6, 17.5, 13.3. HRMS (ESI): calculated for C 20 H 30 N2O 10 Na ([M + Na] + ): 481.1793, found: 481.1781.

[0240]

Chemical Formula

[0241] [Example 2] <Production of Compound (1)-102 (Diethyl 4-(((2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)carbamoyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate)> N-((2R,3R,4R,5S,6R)-2-amino-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)acetamide (compound (11)-102, 206 mg, 0.936 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 16 mL). The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 235 mg, 0.791 mmol) and N,N'-dicyclohexylcarbodiimide (DCC, 405 mg, 1.96 mmol) were added thereto. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the reaction was carried out by stirring the mixture at that temperature for 22 hours. Next, the solvent in the resulting reaction solution was removed as an azeotropic mixture with toluene, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 85 / 15~78 / 22 (volume ratio)) and flash ODS column chromatography (mobile phase: water / methanol = 60 / 40~36 / 64 (volume ratio)). Based on the above, the target compound (1)-102 was obtained as a pale yellow solid (yield 212 mg, yield 53%).

[0242] The obtained compound is compound (1)-102. 1 1H NMR, 13 This was confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time is shown below. 11H NMR (600 MHz, CD3OD) δ (ppm): 4.81 (d, J = 9.8 Hz, 1H), 4.56 (s, 1H), 4.28 - 4.19 (m, 4H), 3.85 - 3.83 (m, 1H), 3.77 (t, J = 10.1 Hz, 1H), 3.67 (dd, J = 12.0, 5.0, 1H), 3.45 (dd, J = 10.1, 8.5 Hz, 1H), 3.32 - 3.31 (m, 2H), 2.31 (s, 6H), 2.00 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 175.8, 173.0, 167.8, 167.7, 148.0, 147.7, 97.3, 96.9, 79.7, 78.4, 74.7, 70.5, 61.3, 59.9, 59.9, 54.3, 41.4, 21.4, 17.6, 17.4, 13.4, 13.4. HRMS (ESI): calculated for C 22 H 33 N3O 10 Na ([M + Na] + ): 522.2058, found: 522.2063.

[0243]

Chem.

[0244] [Example 3] <Production of Compound (1)-103 (Diethyl 4-(((2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)carbamoyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate)> 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 340 mg, 1.14 mmol) and N-methylmorpholine (NMM, 0.25 mL, 2.69 mmol) were dissolved in dichloromethane (30 mL). The resulting solution was cooled to 0°C, and isobutyl chloroformate (0.15 mL, 1.06 mmol) was added. The resulting liquid mixture was then stirred for 30 minutes while maintaining its temperature at 0°C. Next, lactosylamine (compound (11)-103, 317 mg, 0.93 mmol) and N,N-dimethylformamide (DMF, 30 mL) were added, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 17 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 90 / 10 to 60 / 40 (volume ratio)) and recycled preparative gel permeation chromatography (GPC) (mobile phase: chloroform / methanol = 50 / 50 (volume ratio)). Based on the above, the target compound (1)-103 was obtained as a white solid (yield 114 mg, yield 20%).

[0245] The obtained compound is compound (1)-103. 1 1H NMR, 13 This was confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 4.80 (d, J = 9.0 Hz, 1H), 4.59 (s, 1H), 4.36 (d, J = 7.8 Hz, 1H), 4.22-4.18 (m, 4H), 3.83-3.42 (m, 12H), 2.29 (s, 6H), 1.31 (t, J = 7.2 Hz, 3H), 1.30 (t, J = 7.2 Hz, 3H). 13C NMR (151 MHz, CD3OD)δ(ppm): 177.5, 169.7, 149.6, 149.4, 105.1, 98.6, 98.3, 81.3, 78.2, 77.2, 77.0, 74.7, 73.9, 72.5, 70.4, 62.5, 61.48, 61.47, 42.9, 19.0, 18.9, 14.75, 14.74. HRMS (ESI): calculated for C 22 H 33 N3O 10 Na ([M + Na] + ): 522.2058, found: 522.2063.

[0246] [ka]

[0247] [Example 4] <Preparation of Compound (1)-104 (Dibenzyl 2,6-dimethyl-4-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)carbamoyl)-1,4-dihydropyridine-3,5-dicarboxylate)> Glucosylamine (compound (11)-101, 137 mg, 0.324 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 5 mL), and the resulting solution was cooled to 0°C. To this solution, 3,5-bis(benzyloxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-102, 75.8 mg, 0.423 mmol) and N,N'-diisopropylcarbodiimide (DIC, 0.14 mL, 1.35 mmol) were added. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 16 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 100 / 0~90 / 10 (volume ratio)). Based on the above, the target compound (1)-104 was obtained as an amorphous solid (yield 55.6 mg, yield 29%).

[0248] The obtained compound is compound (1)-104. 1 1H NMR, 13 This was confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 7.62 (d, J = 8.4 Hz, 1H), 7.40-7.28 (m, 10H), 5.21-5.14 (m, 4H), 4.78 (t, J = 9.0 Hz, 1H), 4.68 (s, 1H), 3.80 (dd, J = 12.0, 1.8 Hz, 1H), 3.62 (dd, J = 12.0, 4.8 Hz, 1H), 3.37 (t, J = 9.0 Hz, 1H), 3.30-3.26 (m, 2H), 3.08 (t, J = 9.0 Hz, 1H), 2.270 (s, 3H), 2.265 (s, 3H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 176.1, 168.2, 168.2, 148.2, 147.9, 97.3, 96.9, 80.1, 78.4, 77.6, 72.9, 70.0, 61.4, 60.0, 60.0, 41.4, 17.6, 17.5, 13.3. HRMS (ESI): calculated for C 26 H 40 N2O 15 Na ([M + Na] + ): 643.2321, found: 643.2318.

[0249] [ka]

[0250] [Example 5] <<Preparation of compound (3) (use of compound (1))>> Compound (1)-101 (23.0 mg, 0.0502 mmol) obtained in Example 1 and compound (2)-101 (dehydroalanine derivative) (22.8 mg, 0.0604 mmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a tetrahydrofuran (THF) solution of the photo-oxidation-reduction catalyst (4CzIPN) represented by the following formula (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the contents were stirred at room temperature for 16 hours while being irradiated with light (wavelength: approximately 360-520 nm) using a blue light-emitting diode (Kessil A 160 WE Tuna blue) to carry out the reaction. The irradiated light had a wavelength range of 360-510 nm, with an intensity peak around 460 nm. Next, the resulting reaction solution was concentrated under reduced pressure to obtain a sugar amide compound (compound (3)) represented by the following formula (3)-101. 1,3-dinitrobenzene was used as an internal standard. 1 The yield of compound (3)-101, calculated from the 1H NMR analysis data, was 94% (S-isomer / R-isomer = 1.1 / 1.0). Here, the S-isomer / R-isomer ratio represents the ratio at the site corresponding to the amino acid origin in the sugar amide compound, and this is consistent with other examples that follow.

[0251] [ka]

[0252] The obtained compound is compound (3)-101. 1 1H NMR, 13The differences were confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time are shown below for each isomer.

[0253] [ka]

[0254] 1 H NMR (600 MHz, DMSO-d6)δ(ppm): 8.49 (d, J = 9.1 Hz, 1H), 7.38-7.31 (m, 5H), 5.49 (dd, J = 7.0, 5.0 Hz, 1H), 5.13 (s, 2H), 4.98 (d, J = 4.9 Hz, 1H), 4.88 (d, J = 5.2 Hz, 1H), 4.84 (d, J = 5.2 Hz, 1H), 4.72, (t, J = 9.1 Hz, 1H), 4.49 (t, J = 5.8 Hz, 1H), 3.64 (ddd, J = 11.8, 5.5, 1.9Hz, 1H), 3.45-3.61 (m, 1H), 3.19-3.16 (m, 1H), 3.13-3.03 (m, 4H), 2.51-2.48 (m, 1H), 1.39 (s, 18H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 170.3, 169.9, 152.0, 151.9, 136.2, 128.8, 128.5, 128.1, 83.2, 80.1, 79.0, 77.9, 73.1, 70.3, 66.8, 61.3, 54.4, 37.0, 27.9. HRMS (ESI): calculated for C 27 H 40 N2O 12 Na ([M + Na] + ): 607.2473, found: 607.2473.

[0255] [ka]

[0256] 1 H NMR (600 MHz, DMSO-d6)δ(ppm): 8.51 (d, J = 8.9 Hz, 1H), 7.38-7.31 (m, 5H), 5.45 (t, J = 6.1 Hz, 1H), 5.14 (d, J = 12.7, 1H), 5.12 (d, J = 12.7 Hz, 1H), 4.99 (d, J = 4.8 Hz, 1H), 4.88 (d, J = 5.3 Hz, 1H), 4.80 (d, J = 5.3 Hz, 1H), 4.72, (t, J = 9.0 Hz, 1H), 4.47 (t, J = 5.8 Hz, 1H), 3.62 (ddd, J = 11.7, 5.6, 1.9 Hz, 1H), 3.44-3.40 (m, 1H), 3.21-3.17 (m, 1H), 3.15-3.03 (m, 4H), 2.55-2.51 (m, 1H), 1.39 (s, 18H). 13 C NMR (151 MHz, DMSO-d6)δ(ppm): 170.3, 170.0, 152.0, 151.9, 136.2, 128.8, 128.5, 128.1, 83.2, 80.1, 79.0, 77.9, 73.0, 70.4, 66.8, 61.3, 54.7, 36.8, 27.9. HRMS (ESI): calculated for C 27 H 40 N2O 12 Na ([M + Na] + ): 607.2473, found: 607.2473.

[0257] [Example 6] Compound (1)-102 (25.0 mg, 0.050 mmol) obtained in Example 2 and compound (2)-101 (dehydroalanine derivative) (22.9 mg, 0.0607 mmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of the photo-oxidation-reduction catalyst (3DPAFIPN) represented by the following formula (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 89 / 11 to 71 / 19 (volume ratio)). Based on the above, a compound represented by the following general formula (3)-102 was obtained as a sugar amide compound (compound (3)) as a pale yellow solid (yield 27.6 mg, yield 88%, S-isomer / R-isomer = 1.3 / 1.0).

[0258] The obtained compound is compound (3)-102. 1 1H NMR, 13 This was confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 7.39-7.33 (m, 5H), 5.57-5.53 (m, 1H), 5.18-5.15 (m, 2H), 4.98 (dd, J = 9.7, 1.6 Hz, 1H), 3.85 (d, J = 12.2 Hz, 1H), 3.80-3.75 (m, 1H), 3.71-3.68 (m, 1H), 3.50-3.45 (m, 1H), 3.37-3.35 (m, 2H), 3.20-3.13 (m, 1H), 2.67 (dd, J = 16.3, 6.8 Hz, 0.56H), 2.56 (dd, J = 15.7, 5.3 Hz, 0.44H), 2.03 (s, 1.32H), 1.97 (s, 1.68H), 1.46 (s, 18H). 13C NMR (151 MHz, CD3OD)δ(ppm): 173.45, 172.9, 171.4, 171.3, 170.0, 169.8, 151.9, 151.8, 135.7, 135.6, 128.2, 128.0, 127.9, 127.9, 127.8, 83.4, 83.4, 79.1, 79.0, 78.3, 78.3, 75.0, 74.9, 70.4, 70.4, 66.9, 66.7, 61.3, 54.8, 54.8, 54.7, 36.7, 36.5, 26.8, 21.6, 21.5. HRMS (ESI): calculated for C 29 H 43 N3O 12 Na ([M + Na] + ): 648.2739, found: 648.2737.

[0259] [ka]

[0260] [Example 7] Compound (1)-103 (14.9 mg, 0.0240 mmol) obtained in Example 3 and compound (2)-101 (dehydroalanine derivative) (10.9 mg, 0.0289 mmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (concentration 1.25 mM, 0.48 mL, 0.60 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 88 / 12 to 71 / 19 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-103 was obtained as a colorless solid (yield 10.2 mg, yield 57%).

[0261] The obtained compound is compound (3)-103. 1 1H NMR, 13 This was confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 7.40-7.33 (m, 5H), 5.62-5.58 (m, 1H), 5.19 (s, 2H), 4.38 (dd, J = 11.3, 1.8 Hz, 1H), 4.95-4.92 (m, 1H), 3.86-3.78 (m, 4H), 3.74-3.70 (m, 1H), 3.62-3.55 (m, 4H), 3.51-3.47 (m, 2H), 3.37-3.30 (m, 1H), 3.30-3.22 (m, 1H), 2.77-2.69 (m, 1H), 1.46 (s, 18H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 172.0, 171.9, 170.1, 170.1, 151.9, 151.9, 135.6, 135.6, 128.2, 127.9, 127.9, 127.9, 127.9, 103.7, 103.7, 83.4, 83.4, 79.7, 79.6, 78.9, 78.8, 76.7, 76.7, 76.0, 75.9, 75.7, 73.4, 72.2, 71.2, 68.9, 66.9, 66.8, 61.1, 60.3, 54.9, 54.7, 36.6, 36.5, 26.8, 26.8. HRMS (ESI): calculated for C 33 H 50N2O 17 Na ([M + Na] + ): 769.3002, found: 769.2997.

[0262] [ka]

[0263] [Example 8] Compound (1)-101 (22.9 mg, 0.050 mmol) obtained in Example 1 and compound (2)-102 (dehydroalanine derivative) (15.1 mg, 0.061 mmol) obtained in Production Example 7 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified twice by flash silica gel column chromatography (mobile phase: chloroform / methanol = 71 / 29~64 / 36 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-104 was obtained as a colorless solid (yield 16.7 mg, yield 73%).

[0264] The obtained compound is compound (3)-104. 1 1H NMR, 13 This was confirmed by 13C NMR and HRMS (ESI). The analytical data obtained at this time is shown below. 11H NMR (600 MHz, D2O) δ (ppm): 7.04 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 8.5 Hz, 2H), 4.84 (dd, J = 9.2, 5.9 Hz, 1H), 4.51 (dt, J = 7.0, 3.2 Hz, 1H), 3.77 (d, J = 12.4 Hz, 1H), 3.62 (dd, J = 12.4, 5.3 Hz, 1H), 3.44 (t, J = 9.1 Hz, 1H), 3.41 (m, 1H), 3.35 - 3.32 (m, 3H), 3.28 (m, 1H), 2.67 - 2.54 (m, 4H), 1.88 (s, 1.5H), 1.88 (s, 1.5H). 13 13C NMR (151 MHz, D2O) δ (ppm): 173.9, 173.9, 172.9, 172.9, 172.2, 172.1, 153.8, 131.0, 130.3, 115.3, 79.2, 79.1, 77.5, 76.4, 76.4, 71.7, 72.7, 69.2, 60.5, 50.3, 50.2, 40.6, 36.8, 36.8, 35.5, 21.7. HRMS (ESI): calculated for C 20 H 29 N3O9Na ([M + Na] + ): 478.1796, found: 478.1798.

[0265]

Chem.

[0266] [Examples 9 - 16] <<Production of Compound (3) (Investigation of Solvent Types)>> Compound (3)-101 was obtained in the same manner as in Example 5, except that the solvent species of the photo-oxidation-reduction catalyst solution was replaced with the same amount (mL) of acetonitrile (CH3CN) (Example 9), N,N-dimethylformamide (DMF) (Example 10), ethyl acetate (SiO) (Example 11), dichloromethane (CH2Cl2) (Example 12), 1,4-dioxane (Example 13), acetone (Example 14), THF / water (1 / 1, volume ratio) (Example 15), or CH3CN / water (1 / 1, volume ratio) (Example 16). Compound (3)-101 obtained in each example was obtained in the same manner as in Example 5. 1 1H NMR, 13 The 13C NMR and HRMS (ESI) analysis data were the same as in Example 5. Table 1 shows the yield of compound (3)-101 and the S / R ratio for each example, calculated using the same method as in Example 5, along with the results for Example 5. Furthermore, in Examples 9, 11, and 12, compound (3)-101 was isolated using the same method as in Example 6, and the isolation yield was also determined. The results are shown in Table 1.

[0267] [Table 1]

[0268] As is clear from the above results, compound (3)-101 was obtained in good yield even when different types of solvents were used. In other words, the preparation of compound (3) using compound (1) was highly versatile, as various reaction solvents could be used.

[0269] [Examples 17-23] <<Production of compound (3) (examination of catalysts)>> As photo-oxidation-reduction catalysts, instead of 4CzIPN, the same molar amounts of 3DPAFIPN (Example 17), Ir(ppy)3 (Example 18), Ir(ppy)3(dtbbpy)PF6 (Example 19), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (Example 20), and Acrylic Acid were used. +Compound (3)-101 was obtained in the same manner as in Example 5, except that -diOR (Example 21), benzophenothiazine (Example 22), or tetrabromofluorescein (Example 23) was used. 1 1H NMR, 13 The 13C NMR and HRMS (ESI) analysis data were the same as in Example 5. Table 2 shows the yield of compound (3)-101 and the S / R ratio for each example, calculated using the same method as in Example 5, along with the results for Example 5.

[0270] [ka]

[0271] [Table 2]

[0272] As is clear from the above results, compound (3)-101 was obtained in good yield even when different types of photocatalysts were used. In other words, the production of compound (3) using compound (1) was highly useful because catalytic activity could be obtained even when various types of photocatalysts were used.

[0273] [Example 24] <<Production of compound (3) (without catalyst)>> Compound (1)-101 (23.0 mg, 0.0502 mmol) obtained in Example 1 and compound (2)-101 (dehydroalanine derivative) (22.8 mg, 0.0604 mmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and THF (1.0 mL) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with a blue light-emitting diode (Kessil A 160 WE Tuna blue) in the same manner as in Example 5. Next, the resulting reaction solution was concentrated under reduced pressure to obtain compound (3)-101 as a colorless solid (21% yield) as a sugar amide compound (compound (3)). The obtained compound (3)-101 1 1H NMR, 13 The 13C NMR and HRMS (ESI) analysis data were the same as in Example 5. The yield of compound (3)-101, calculated using the same method as in Example 5, was 21% (S-isomer / R-isomer = 1.0 / 1.1). Thus, compound (3)-101 was obtained without using a photocatalyst.

[0274] [ka]

[0275] [Example 25] <<Production of Compound (1)>> <Preparation of Compound (1)-105 (Diethyl 2,6-dimethyl-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)carbamoyl)-1,4-dihydropyridine-3,5-dicarboxylate)> D-galactose (180 mg, 1.00 mmol) was dissolved in a mixture of methanol / 28% aqueous ammonia (1 / 4, volume ratio) (2.5 mL). This solution was heated to 40°C, and ammonium carbamate (157 mg, 2.01 mmol) was added. The mixture was stirred at 40°C for 24 hours. The resulting reaction mixture was then cooled to room temperature, and ammonium carbamate (156 mg, 2.00 mmol) was added. The resulting mixture was stirred at room temperature for another 16 hours. N,N-diisopropylethylamine (200 μL) was then added to the reaction mixture, and the solvent was removed from the resulting mixture by vacuum concentration. The resulting concentrate was dissolved in water, and the resulting solution was freeze-dried. 2-propanol was added to the resulting dry product, and the solvent was removed by vacuum concentration to obtain compound (11)-104.

[0276] The resulting compound (11)-104 (β-glycosylamine, 310 mg, 1.72 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 26 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 513 mg, 1.72 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 990 mg, 5.16 mmol) were added to it. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 90 / 10~79 / 21 (volume ratio)) and flash ODS column chromatography (mobile phase: water / methanol = 87 / 13~79 / 21 (volume ratio)). Based on the above, the target compound (1)-105 was obtained as a pale yellow solid (yield 207 mg, yield 26%).

[0277] The obtained compound is compound (1)-105. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and infrared spectroscopy (IR). Furthermore, the specific rotation of compound (1)-105 was measured. The analytical data obtained at this time are shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 4.76 (d, J = 8.8 Hz, 1H), 4.62 (s, 1H), 4.26-4.19 (m, 4H), 3.88 (d, J = 3.2 Hz, 1H), 3.70 (dd, J = 11.3, 6.6 Hz, 1H), 3.66 (dd, J = 11.3, 5.4 Hz, 1H), 3.57-3.53 (m, 2H), 3.50 (dd, J = 9.4, 3.2 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.32 (t, J = 7.1 Hz, 3H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 176.0, 168.2, 168.2, 148.2, 147.9, 97.3, 96.9, 80.5, 77.0, 74.3, 69,1, 61.2, 60.1, 60.0, 41.3, 17.6, 17.5, 13.3. HRMS (ESI): calculated for C 20 H 30 N2O 10 Na ([M + Na] + ): 481.1793, found: 481.1791. [α] D 25 = -4.24 (c = 0.230, MeOH). IR (ATR, cm- 1): 1716.3, 1673.0, 1658.5, 1621.9, 1531.2, 1484.0, 13375.0, 1262.2, 1207.2, 1120.4, 1047.2, 1010.5, 847.6, 767.5, 654.7.

[0278] [ka]

[0279] [Example 26] <Preparation of Compound (1)-106 (Diethyl 4-(((2R,3R,4R,5R,6R)-3-Acetamido-4,5-Dihydroxy-6-(Hydroxymethyl)tetrahydro-2H-pyran-2-yl)carbamoyl)-2,6-Dimethyl-1,4-Dihydropyridine-3,5-Dicarboxylate)> N-acetylgalactosamine was prepared using the method described in the paper "Beilstein J. Org. Chem., 2018, 14, 856." The obtained N-acetylgalactosamine (88.5 mg, 0.400 mmol) was dissolved in methanol (1.0 mL) to prepare a solution. The temperature of this solution was adjusted to 40°C, and ammonium carbamate (129 mg, 1.65 mmol) was added. The mixture was stirred at 40°C for 18 hours. Next, methanol (approximately 5 mL) and N,N-diisopropylethylamine (100 μL) were added to the resulting reaction mixture. The resulting mixture was concentrated under reduced pressure at 30°C and a pressure of 12 kPa (120 mbar). 2-propanol was added to the resulting concentrate, and the solvent was removed by reduced pressure concentration to obtain compound (11)-105.

[0280] The resulting compound (11)-105 (β-glycosylamine, 208 mg, 0.945 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 14 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 283 mg, 0.952 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 546 mg, 2.85 mmol) were added to it. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 92 / 8~74 / 26 (volume ratio)). Based on the above, the target compound (1)-106 was obtained as a pale yellow solid (yield 62 mg, yield 13%).

[0281] The obtained compound is compound (1)-106. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-106 was measured. The analytical data obtained at this time are shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 8 (d, J = 3.1 Hz, 1H), 3.73 (dd, J = 11.4, 6.5 Hz, 1H), 3.68 (dd, J = 11.4, 5.4 Hz, 1H) 3.58 (dd, J = 10.6, 3.1 Hz, 1H), 3.54 (t, J = 6.2 Hz, 1H), 2.32 (s, 6H), 2.00 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (151 MHz, CD3OD)δ(ppm): 178.0, 175.4, 170.0, 150.2, 150.0, 99.5, 99.3, 99.2, 82.3, 79.3, 74.1, 70.5, 63.5, 62.2, 62.2, 53.2, 43.6, 43.6, 23.7, 19.8, 19.7, 15.7, 15.6. HRMS (ESI): calculated for C 20 H 33 N3O 10 Na ([M + Na] + ): 522.2058, found: 522.2055. [α] D 25 = 34.9 (c = 0.400, MeOH) IR (ATR, cm- 1 ): 1646.9, 1486.9, 1371.1, 1305.6, 1211.1, 1116.6, 1094.4, 1022.1, 771.4.

[0282] [ka]

[0283] [Example 27] <Preparation of Compound (1)-107 (Diethyl 2,6-dimethyl-4-(((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)carbamoyl)-1,4-dihydropyridine-3,5-dicarboxylate)> A solution of D-mannose (180 mg, 1.00 mmol) dissolved in methanol (3.0 mL) was used, and ammonium carbamate (315 mg, 4.00 mmol) was added to this solution at room temperature and stirred for 42 hours at room temperature. Next, the solvent was removed from the resulting reaction mixture by vacuum concentration, and the resulting concentrate was dissolved in water. N,N-diisopropylethylamine (200 μL) was then added, and the resulting mixture was freeze-dried to obtain compound (11)-106.

[0284] The resulting compound (11)-106 (β-glycosylamine, 138 mg, 0.767 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 12 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 229 mg, 0.770 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 450 mg, 2.34 mmol) were added to it. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 85 / 15~78 / 22 (volume ratio)). Based on the above, the target compound (1)-107 was obtained as a pale yellow solid (yield 112 mg, yield 32%).

[0285] The obtained compound is compound (1)-107. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-107 was measured. The analytical data obtained at this time are shown below. 11H NMR (600 MHz, CD3OD) δ (ppm): 5.08 (d, J = 1.2 Hz, 1H), 4.63 (s, 1H), 4.25 - 4.17 (m, 4H), 3.83 (dd, J = 11.8, 2.3 Hz, 1H), 3.74 (dd, J = 3.5, 1.2 Hz, 1H), 3.68 (dd, J = 11.8, 5.8 Hz, 1H), 3.56 (dd, J = 9.4, 9.4 Hz, 1H) 3.51 (dd, J = 9.4, 3.3 Hz, 1H), 3.26 (ddd, J = 9.4, 5.8, 2.3 Hz, 1H), 2.33 (s, 3H), 2.32 (s, H), 1.34 (t, J = 7.1 Hz, 3H), 1.32 (t, J = 7.1 Hz, 4H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 174.8, 168.0, 167.8, 148.3, 148.0, 97.2, 96.7, 78.5, 77.7, 74.4, 71.0, 66.7, 61.5, 60.1, 59.9, 41.0, 17.5, 17.3, 13.3, 13.3. HRMS (ESI): calculated for C 20 H 30 N2O 10 Na ([M + Na] + ): 481.1793, found: 481.1799. [α] D 25 = -38.0 (c = 0.530, MeOH). IR (ATR, cm- 1 ): 1660.4, 1619.9, 1522.5, 1484.9, 1372.1, 1307.5, 1266.0, 1207.2, 1119.5, 1052.9, 1019.3, 767.5.

[0286]

Chem.

[0287] [Example 28] <Preparation of Compound (1)-108 (Diethyl 2,6-dimethyl-4-(((2R,3R,4S,5R)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)carbamoyl)-1,4-dihydropyridine-3,5-dicarboxylate)> A solution was prepared by dissolving D-xylose (60.1 mg, 0.400 mmol) in a methanol / 28% aqueous ammonia (50 / 1 volume ratio) (1.6 mL). The temperature of this solution was set to 40°C, and ammonium carbamate (126 mg, 1.61 mmol) was added. The mixture was stirred at 40°C for 19 hours. Then, methanol (approximately 5 mL) and N,N-diisopropylethylamine (200 μL) were added to the resulting reaction mixture. The resulting mixture was concentrated under reduced pressure at 30°C and a pressure of 12 kPa (120 mbar). 2-propanol was added to the resulting concentrate, and the solvent was removed by reduced pressure concentration to obtain compound (11)-107.

[0288] The resulting compound (11)-107 (β-glycosylamine, 209 mg, 1.40 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 21 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 417 mg, 1.40 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 810 mg, 4.23 mmol) were added to it. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 90 / 10~82 / 18 (volume ratio)) and flash ODS column chromatography (mobile phase: water / methanol = 80 / 20~38 / 62 (volume ratio)). Based on the above, the target compound (1)-108 was obtained as a pale yellow solid (yield 215 mg, yield 36%).

[0289] The obtained compound is compound (1)-108. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-108 was measured. The analytical data obtained at this time are shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 4.78 (d, J = 8.3 Hz, 1H), 4.59 (s, 1H), 4.25-4.18 (m, 4H), 3.82 (dd, J = 11.5, 5.0 Hz, 1H), 3.48 (dt, J = 9.4, 5.0 Hz, 1H), 3.37 (d, J = 7.6 Hz, 1H), 3.27-3.22 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 1.32 (t, J = 7.0 Hz, 3H), 1.31 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 175.8, 168.2, 168.1, 148.2, 148.0, 97.3, 97.0, 80.4, 76.6, 72.5, 69.7, 66.6, 60.0, 60.0, 41.5, 17.6, 17.5, 13.3, 13.3. HRMS (ESI): calculated for C 19 H 28 N2O9Na ([M + Na] +): 451.1687, found: 451.1694. [α] D 25 = -9.98 (c = 0.250, MeOH). IR (ATR, cm- 1 ): 1653.7, 1484.0, 1369.0, 1323.6, 1263.2, 1208.2, 1119.5, 1089.6, 1045.2, 1015.3, 764.6.

[0290] [ka]

[0291] [Example 29] <Preparation of Compound (1)-109 (Diethyl 2,6-dimethyl-4-(((2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)carbamoyl)-1,4-dihydropyridine-3,5-dicarboxylate)> A solution of L-rhamnose monohydrate (182 mg, 1.00 mmol) dissolved in methanol (2.5 mL) was prepared, and the temperature of this solution was set to 20°C. Ammonium carbamate (312 mg, 4.00 mmol) was added to this solution, and the mixture was stirred at 20°C for 42 hours. Next, the solvent was removed from the resulting reaction mixture by vacuum concentration, and the resulting concentrate was dissolved in water. N,N-diisopropylethylamine (200 μL) was then added, and the resulting mixture was freeze-dried to obtain compound (11)-108.

[0292] The resulting compound (11)-108 (β-glycosylamine, 128 mg, 0.783 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 12 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 238 mg, 0.800 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 453 mg, 2.36 mmol) were added to it. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the solvent in the resulting reaction solution was removed three times as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 95 / 5~84 / 16 (volume ratio)). Based on the above, the target compound (1)-109 was obtained as a pale yellow solid (yield 185 mg, yield 56%).

[0293] The obtained compound is compound (1)-109. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-109 was measured. The analytical data obtained at this time are shown below. 11H NMR (600 MHz, CD3OD) δ (ppm): 5.05 (d, J = 1.1 Hz, 1H), 4.62 (s, 1H), 4.24 - 4.17 (m, 4H), 3.82 (dd, J = 12.0, 2.0 Hz, 1H), 3.64 (dd, J = 12.0, 5.0 Hz, 1H), 3.38 (t, J = 8.8 Hz, 1H), 3.32 - 3.28 (m, 2H), 3.22 (t, J = 9.1 Hz, 1H), 2.31 (s, 3H), 2.31 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 176.1, 168.2, 168.2, 148.2, 147.9, 97.3, 96.9, 80.1, 78.4, 77.6, 72.9, 70.0, 61.4, 60.0, 60.0, 41.4, 17.6, 17.5, 13.3. HRMS (ESI): calculated for C<000​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​To a 15 mL aqueous solution of ammonium bicarbonate in which D-maltose monohydrate (726 mg, 2.12 mmol) was dissolved, ammonium bicarbonate (5.10 g) was added at room temperature. The resulting mixture was heated to 40°C and stirred for 2 days. After the reaction was complete, the reaction solution was concentrated under reduced pressure to remove the solvent. The resulting residue was dissolved in a water / methanol mixed solvent, concentrated again under reduced pressure, and this procedure was repeated until all ammonium bicarbonate was removed. The resulting β-glycosylamine (compound (11)-109, 730 mg, 2.14 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 30 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 594 mg, 2.00 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 1.16 g, 6.05 mmol) were added to it. Next, the temperature of the resulting liquid mixture was raised to room temperature, and the mixture was stirred at that temperature for 40 hours to carry out the reaction. Next, the resulting reaction mixture was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 75 / 25~68 / 32 (volume ratio)) and flash ODS column chromatography (mobile phase: water / methanol = 74 / 26~49 / 51 (volume ratio)). As a result, the target compound (1)-110 was obtained as a pale yellow solid (yield 721 mg, total yield of 58% in the two steps).

[0296] The obtained compound is compound (1)-110. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-110 was measured. The analytical data obtained at this time are shown below. 1H NMR (600 MHz, CD3OD)δ(ppm): 5.19 (d, J = 3.8 Hz, 1H), 4.81 (d, J = 9.1 Hz, 1H), 4.60 (s, 1H), 4.26-4.19 (m, 4H), 3.85-3.83 (m, 2H), 3.79 (dd, J = 12.2, 4.3 Hz, 1H), 3.72-3.62 (m, 4H), 3.56 (dd, J = 9.3, 9.3 Hz, 1H), 3.46 (dd, J = 9.7, 3.8 Hz, 1H), 3.41 (ddd, J = 9.7, 4.0, 1.9 Hz, 1H), 3.37 (s, 2H), 3.29 (dd, J = 9.3, 9.3 Hz, 1H), 3.28 (dd, J = 9.3, 9.3 Hz, 1H) 2.31 (s, 3H), 2.31 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 4H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 176.0, 168.2, 168.2, 148.2, 147.9, 101.5, 97.3, 96.9, 80.0, 79.6, 77.4, 77.0, 73.7, 73.4, 72.8, 72.5, 70.1, 61.3, 60.7, 60.1, 60.0, 41.5, 17.6, 17.5, 13.4, 13.4. HRMS (ESI): calculated for C 26 H 40 N2O 15 Na ([M + Na] + ): 643.2321, found: 643.2327. [α] D 25 = 41.0 (c = 0.330, MeOH). IR (ATR, cm- 1 ): 1653.7, 1487.8, 1369.1, 1305.6, 1212.0, 1072.2, 1015.3, 766.6

[0297] [ka]

[0298] [Example 31] <Production of Compound (1)-111> In an aqueous solution (8 mL) containing maltopentaose (351 mg, 0.399 mmol) dissolved in a saturated aqueous solution of ammonium bicarbonate, ammonium bicarbonate (6.00 g) was added at room temperature. The resulting mixture was heated to 40°C and stirred for 39 hours. After the reaction was complete, the reaction solution was freeze-dried. The resulting residue was dissolved in water and freeze-dried again, and this procedure was repeated until all ammonium bicarbonate was removed. The resulting β-glycosylamine (compound (11)-110, 343 mg, 0.414 mmol) was dissolved in a pyridine / water (4 / 1 (volume ratio), 4 mL) mixed solvent without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 123 mg, 0.414 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl, 244 mg, 1.27 mmol) were added to it. Next, the temperature of the resulting liquid mixture was kept at 0°C, and the reaction was carried out by stirring the mixture for 16 hours. Next, the solvent in the resulting reaction solution was removed as an azeotropic mixture with toluene, and this process was repeated three times. The resulting residue was then purified by two flash ODS column chromatography cycles (1st cycle: mobile phase: water / methanol = 95 / 5~0 / 100 (volume ratio), 2nd cycle: mobile phase: water / methanol = 75 / 25~50 / 50 (volume ratio)). As a result, the target compound (1)-111 was obtained as a pale yellow solid (yield 194 mg, total yield of 44% in the two steps).

[0299] The obtained compound is compound (1)-111. 1 1H NMR, 13The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-111 was measured. The analytical data obtained at this time are shown below. 1 H NMR (600 MHz, D2O)δ(ppm): 5.20 (d, J = 3.8 Hz, 1H), 5.18-5.16 (m, 3H), 4.81 (d, J = 9.1 Hz, 1H), 4.60 (s, 1H), 4.26-4.19(m, 4H), 3.90-3.87 (m, 3H), 3.85-3.75 (m, 12H), 3.72-3.62 (m, 4H), 3.57-3.50 (m, 7H), 3.46 (dd, J = 9.7, 3.7 Hz, 1H), 3.42 (ddd, J = 9.7, 4.2, 1.9 Hz, 1H), 3.29 (t, J = 9.2, 1H), 3.28 (t, J = 9.4 Hz, 1H), 2.31 (s, 3H), 2.31 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 4H). 13 C NMR (151 MHz, D2O)δ(ppm): 176.0, 168.2, 168.2, 148.2, 147.9, 101.5, 101.3, 101.2, 101.2, 97.3, 96.9, 80.0, 79.9, 79.9, 79.6, 77.4, 77.0, 73.7, 73.5, 73.4, 72.9, 72.5, 72.5, 72.4, 71.9, 70.1, 61.3, 60.7, 60.0, 60.0, 41.5, 17.6, 17.5, 13.4, 13.3. HRMS (ESI): calculated for C 44 H 70 N2O 30 Na ([M + Na] + ): 1129.3906, found: 1129.3948. [α] D 25 = 99.7 (c = 0.200, H2O) IR (ATR, cm- 1 ): 1664.3, 1369.2, 1310.4, 1216.9, 1077.1, 1019.2, 766.6.

[0300] [ka]

[0301] [Example 32] <Production of Compound (1)-112> In a saturated aqueous solution of ammonium bicarbonate, 88.6 mg (0.135 mmol) of 3'-sialyl lactose sodium salt was dissolved (4.4 mL). Ammonium bicarbonate (3.60 g) was then added at room temperature. The resulting mixture was heated to 40°C and stirred for 97 hours. After the reaction was complete, the reaction solution was freeze-dried. The resulting residue was dissolved in water and freeze-dried again. This process was repeated until all ammonium bicarbonate was removed. The resulting β-glycosylamine (compound (11)-111, 88.7 mg, 0.136 mmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 2.7 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 81.1 mg, 0.296 mmol) and N,N'-dicyclohexylcarbodiimide (DCC, 555 mg, 3.36 mmol) were added to it. Next, the temperature of the resulting liquid mixture was kept at 0°C, and the reaction was carried out by stirring the mixture for 23 hours. Next, the solvent in the resulting reaction solution was removed once as an azeotropic mixture with toluene. The resulting residue was then purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 80 / 20~40 / 60 (volume ratio)) and flash ODS column chromatography (mobile phase: water / methanol = 100 / 0~75 / 25 (volume ratio)). When performing the latter flash ODS column chromatography, a 0.5 M aqueous sodium bicarbonate solution was used to feed the residue onto the column. As a result, the target compound (1)-112 was obtained as a pale yellow solid (yield 64.3 mg, total yield of 51% in the two steps).

[0302] Compound (1)-112 has a structure in which the hydrogen atom constituting the hydroxyl group at the 3' position of lactose is substituted by a monovalent group having a structure in which the hydroxyl group at the anomeric position of the sodium sialate salt has been removed.

[0303] The obtained compound is compound (1)-112. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-112 was measured. The analytical data obtained at this time are shown below. 1 H NMR (600 MHz, D2O)δ(ppm): 4.80 (d, J = 9.2 Hz, 1H), 4.46 (s, 1H), 4.44 (d, J = 7.9 Hz, 1H), 4.16-4.07 (m, 4H), 4.02 (dd, J = 9.8, 3.1 Hz, 1H), 3.87 (d, J = 3.1 Hz, 1H), 3.84-3.47 (m, 16H), 3.37 (m, 1H), 2.67 (dd, J = 12.3, 4.7 Hz, 1H), 2.18 (s, 3H), 2.18 (s, 3H), 1.94 (s, 3H), 1.71 (t, J = 12.2 Hz, 1H), 1.19 (q, J = 7.0 Hz, 6H). 13C NMR (151 MHz, D2O)δ(ppm): 177.9, 175.0, 173.9, 169.5, 169.4, 149.7, 149.4, 102.6, 99.8, 96.9, 96.7, 79.4, 77.9, 76.3, 75.4, 75.2, 75.2, 69.3, 68.3, 68.1, 67.4, 62.5, 61.3, 61.2, 61.0, 60.0, 51.6, 41.9, 39.6, 22.0, 18.2, 18.1, 13.6, 13.6. HRMS (ESI): calculated for C 37 H 57 N3O 23 Na ([M + H] + ): 934.3275, found: 934.3270. [α] D 25 = -32.7 (c = 0.205, H2O). IR (ATR, cm- 1 ): 1660.4, 1615.1, 1490.7, 1374.0, 1310.4, 1216.9, 1024.0, 769.5, 663.4.

[0304] [ka]

[0305] [Example 33] <Production of Compound (1)-113> To a 15 mL aqueous solution of ammonium bicarbonate in which disialyl octasaccharide (23.0 mg, 11.4 μmol) was dissolved, ammonium bicarbonate (5.00 g) was added at room temperature. The resulting mixture was heated to 40°C and stirred for 14 hours. Then, ammonium bicarbonate (5.00 g) was added to the resulting reaction mixture, and the mixture was stirred at 40°C for 3.5 days. After the reaction was complete, the reaction solution was freeze-dried. The resulting residue was dissolved in water and freeze-dried again, and this procedure was repeated until all ammonium bicarbonate was removed. The resulting β-glycosylamine (compound (11)-112, 26.2 mg, 13.0 μmol) was dissolved in a mixed solvent of pyridine / water (4 / 1 (volume ratio), 1.5 mL) without purification. The resulting solution was cooled to 0°C, and 3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carboxylic acid (compound (12)-101, 34.2 mg, 115 μmol) and N,N'-diisopropylcarbodiimide (DIC, 105 μL, 682 μmol) were added to it. Next, the temperature of the resulting liquid mixture was kept at 0°C, and the reaction was carried out by stirring the mixture for 48 hours. Next, water was added to the resulting reaction mixture, and the aqueous layer was washed twice with chloroform to adjust its pH to approximately 4, making it acidic. The aqueous layer was then washed once more with chloroform. The resulting aqueous layer was freeze-dried, and the resulting residue was purified by preparative high-performance liquid chromatography (mobile phase flow rate: 3.0 mL / min, linear gradient: 0.1 vol% trifluoroacetic acid aqueous solution / acetonitrile (volume ratio) = 98 / 2~60 / 40 (30 min)). Through the above process, the target compound (1)-113 was obtained as a light, soft, white solid (yield 11.9 mg, total yield of 45% in the two steps).

[0306] The obtained compound is compound (1)-113. 1 1H NMR, 13 The compound was confirmed by 13C NMR, HRMS (ESI), and IR. Furthermore, the specific rotation of compound (1)-113 was measured. The analytical data obtained at this time are shown below. 1H NMR (600 MHz, D2O)δ(ppm): 5.04 (s, 1H), 4.88-4.86 (m, 2H), 4.51 (d, J = 7.9 Hz, 2H), 4.46 (s, 1H), 4.36 (dd, J = 7.9, 1.6 Hz, 2H), 4.18-4.08 (m, 6H), 4.03 (m, 1H), 3.95-3.39 (m, 60H), 2.58-2.56 (m, 2H), 2.20 (s, 3H), 2.19 (s, 3H), 1.98 (s, 3H), 1.98 (s, 3H), 1.94 (s, 3H), 1.94 (s, 3H), 1.91 (s, 3H), 1.69 (t, J = 12.2 Hz, 2H), 1.20 (q, J = 7.0, 6H). 13 C NMR (151 MHz, D2O)δ(ppm): 177.3, 174.9, 174.7, 174.5, 172.4, 172.4, 169.3, 169.3, 149.6, 149.4, 103.6, 103.5, 100.5, 99.5, 99.4, 99.4, 99.3, 99.2, 96.9, 96.8, 96.6, 80.7, 80.7, 80.5, 79.7, 78.8, 76.4, 76.2, 76.0, 74.4, 73.6, 73.5, 72.8, 72.7, 72.6, 72.4, 72.1, 72.0, 71.3, 70.7, 70.2, 69.4, 69.4, 68.4, 68.3, 67.8, 67.3, 67.3, 65.8, 65.6, 63.3, 62.8, 61.7, 61.6, 61.3, 61.2, 60.2, 60.0, 54.6, 53.4, 51.8, 41.7, 39.5, 22.4, 22.0, 22.0, 18.1, 18.0, 13.6, 13.6. HRMS (ESI): calculated for C 90 H 145 N7O 61 ([M + 2H] 2+ ): 1149.9224, found: 1149.9218. [α]D 25 = -9.31 (c = 0.100, H2O) IR (ATR, cm- 1 ): 1639.2, 1560.1, 1430.9, 1374.0, 1307.5, 1031.7, 893.8.

[0307] [ka]

[0308] [Example 34] <<Preparation of compound (3) (use of compound (1))>> Compound (1)-105 (25.0 mg, 50.0 μmol) obtained in Example 25 and compound (2)-101 (dehydroalanine derivative) (22.7 mg, 60.1 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 100 / 0~82 / 18 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-105 was obtained as a colorless solid (yield 24.4 mg, yield 83%, S-isomer / R-isomer = 1.2 / 1.0).

[0309] The obtained compound is compound (3)-105. 1 1H NMR, 13Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 7.40-7.33 (m, 5H), 5.60 (dd, J = 12.8, 6.4 Hz, 1H), 5.19 (s, 2H), 4.61 (s, 1H), 3.90 (t, J = 2.8 Hz, 1H), 3.73-3.67 (m, 2H), 3.61-3.52 (m, 3H), 3.27 (m, 1H), 2.73 (m, 1H), 1.49 (s, 18H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 171.9, 171.9, 170.2, 170.1, 152.0, 151.9, 135.6, 135.6, 128.2, 127.9, 127.9, 83.4, 80.3, 80.3, 76.8, 74.4, 74.3, 70.0, 70.0, 69.0, 66.9, 61.1, 61.1, 54.9, 54.8, 36.6, 36.5, 26.8. HRMS (ESI): calculated for C 27 H 40 N2O 12 Na ([M + Na] + ): 607.2473, found: 607.2474. IR (ATR, cm- 1 ): 1734.7, 1690.3, 1542.8, 1458.9, 1361.5, 1226.5, 1135.9, 1077.1, 849.5, 745.4, 695.2.

[0310] [ka]

[0311] [Example 35] Compound (1)-106 (25.0 mg, 50.0 μmol) obtained in Example 26 and compound (2)-101 (dehydroalanine derivative) (22.7 mg, 60.1 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 100 / 0~85 / 15 (volume ratio)). Based on the above, a compound represented by the following formula (3)-106 was obtained as a sugar amide compound (compound (3)) as a pale yellow solid (yield 26.2 mg, yield 84%, S-isomer / R-isomer = 1.2 / 1.0).

[0312] The obtained compound is compound (3)-106. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 11H NMR (600 MHz, CD3OD) δ (ppm): 7.39 - 7.33 (m, 5H), 5.57 - 5.53 (m, 1H), 5.20 - 5.13 (m, 2H), 4.93 (dd, J = 9.7, 3.4 Hz, 1H), 4.07 (dt, J = 15.9, 10.3 Hz, 1H), 3.91 (d, J = 2.9 Hz, 1H), 3.76 - 3.69 (m, 2H), 3.64 - 3.57 (m, 2H), 3.21 - 3.14 (m, 1H), 2.87 (dd, J = 16.3, 6.9 Hz, 0.47H), 2.57 (dd, J = 15.7, 5.3 Hz, 0.53H), 2.03 (s, 1.59H), 1.97 (s, 1.39H), 1.46 (s, 18H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 173.8, 173.2, 171.5, 171.3, 170.0, 169.8, 151.9, 151.8, 135.7, 135.6, 128.2, 127.9, 127.9, 127.9, 127.7, 83.4, 83.4, 79.5, 79.4, 77.0, 76.9, 72.1, 72.0, 68.1, 66.9, 66.7, 61.1, 54.8, 54.8, 51.5, 51.3, 36.6, 36.5, 26.8, 21.6, 21.6. HRMS (ESI): calculated for C 29 H 43 N3O 12 Na ([M + Na] + ): 648.2739, found: 648.2737. IR (ATR, cm- 1 ): 1738.5, 1694.1, 1651.7, 1543.7, 1452.1, 1365.4, 1312.3, 1225.5, 1137.8, 1079.0, 851.4, 750.1 - 2, 697.1.

[0313]

Chem.

[0314] [Example 36] Compound (1)-107 (22.9 mg, 49.9 μmol) obtained in Example 27 and compound (2)-101 (dehydroalanine derivative) (22.9 mg, 60.7 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 95 / 5~84 / 16 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-107 was obtained as a colorless solid (yield 26.3 mg, yield 90%, S-isomer / R-isomer = 1.0 / 1.0).

[0315] The obtained compound is compound (3)-107. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 11H NMR (600 MHz, CD3OD) δ (ppm): 7.39 - 7.33 (m, 5H), 5.60 (dd, J = 7.5, 5.9 Hz, 0.49H), 5.56 (dd, J = 6.6, 6.6 Hz, 0.51H) 5.21 - 5.12 (m, 3H), 4.60 (s, 1H), 3.86 (t, J = 2.0 Hz, 0.49H), 3.84 (t, J = 2.0 Hz, 0.51 Hz), 3.73 - 3.67 (m, 2H), 3.79 - 3.69 (m, 2H), 3567 (m, 1H), 3.53 (m, 1H), 3.30 (m, 1H), 3.25 (m, 1H), 2.79 (dd, J = 16.0, 6.8 Hz, 0.51H), 2.65 (dd, J = 15.8, 5.9 Hz, 0.49H), 1.47 (s, 8.8H), 1.46 (s, 9.2H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 171.1, 171.0, 170.1, 170.0, 152.0, 151.9, 135.6, 135.6, 128.2m 128.2, 128.0, 128.0, 127.9, 83.5, 83.4, 78.5, 78.4, 78.0, 77.9, 74.3, 70.9, 70.8, 66.9, 66.9, 66.7, 66.7, 61.4, 55.0, 54.9, 36.5, 36.5, 26.8, 26.8. HRMS (ESI): calculated for C 27 H 40 N2O 12 Na ([M + Na] + ): 607.2473, found: 607.2469. IR (ATR, cm- 1 ): 1734.7, 1699.9, 1538.9, 1360.5, 1312.3, 1225.5, 1135.9, 1114.7, 1072.2, 851.4, 692.3.

[0316]

Chem.

[0317] [Example 37] Compound (1)-108 (21.5 mg, 50.2 μmol) obtained in Example 28 and compound (2)-101 (dehydroalanine derivative) (22.7 mg, 60.1 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 100 / 0~88 / 12 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-108 was obtained as a colorless solid (yield 25.7 mg, yield 93%, S-isomer / R-isomer = 1.3 / 1.0).

[0318] The obtained compound is compound (3)-108. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 1H NMR (600 MHz, CD3OD)δ(ppm): 7.39-7.32 (m, 5H), 5.60 (m, 1H), 5.18 (ms 2H), 4.83 (dd = 8.9, 5.5 Hz, 1H), 3.83 (m, 2H), 3.49 (m, 1H), 3.33 (m, 1H), 3.30-3.22 (m, 2H), 2.73 (dd, J = 16.0, 6.5 Hz, 1H), 1.46 (s, 18H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 171.8, 171.8, 170.2, 170.0, 152.0, 151.9, 135.6, 128.2, 128.2, 128.0, 127.9, 127.9, 127.9, 83.4, 80.5, 80.4, 77.6, 77.5, 72.5, 69.8, 69.8, 67.3, 66.9, 66.9, 55.0, 54.8, 36.6, 36.6, 26.8. HRMS (ESI): calculated for C 26 H 38 N2O 11 Na ([M + Na] + ): 577.2368, found: 577.2372. IR (ATR, cm- 1 ): 1732.7, 1697.1, 1538.9, 1363.4, 1230.4, 1135.9, 1047.2, 846.6, 737.6, 695.2.

[0319] [ka]

[0320] [Example 38] Compound (1)-109 (21.1 mg, 49.9 μmol) obtained in Example 29 and compound (2)-101 (dehydroalanine derivative) (22.7 mg, 60.1 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 100 / 0~88 / 12 (volume ratio)). Based on the above, a compound represented by the following formula (3)-109 was obtained as a sugar amide compound (compound (3)) as a pale yellow solid (yield 23.5 mg, yield 83%, S-isomer / R-isomer = 1.1 / 1.0).

[0321] The obtained compound is compound (3)-109. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, CD3OD)δ(ppm): 7.39-7.33 (m, 5H), 5.59 (dd, J = 7.4, 6.0 Hz, 0.53H), 5.56 (dd, J = 6.7 Hz, 0.47H), 5.21-5.09 (m, 3H), 3.78 (dd, J = 3.2, 1.0 Hz, 0.47H), 3.72 (d, J = 3.3 Hz, 0.53H), 3.47 (m, 1H), 3.33-3.21 (m, 1H), 2.78 (dd, J = 15.9, 7.0 Hz, 0.47H), 2.66 (dd, J = 15.8, 5.9 Hz, 0.53H), 1.47 (s, 9.5H), 1.46 (s, 8.5H), 1.29 (dd, J = 5.6, 4.3 Hz, 3H). 13C NMR (151 MHz, CD3OD)δ(ppm): 170.9, 170.8, 170.1, 170.0, 151.9, 151.9, 135.6, 135.6, 128.2, 128.2, 128.0, 127.9, 127.9, 83.4, 83.4, 77.8, 77.7, 74.0, 74.0, 73.9, 72.1, 71.0, 70.8, 66.9, 66.9, 55.0, 55.0, 36.5, 36.5, 26.8, 26.8, 16.7, 16.7. HRMS (ESI): calculated for C 27 H 40 N2O 11 Na ([M + Na] + ): 591.2524, found: 591.2523. IR (ATR, cm- 1 ): 1734.7, 1694.2, 1528.3, 1365.4, 1227.5, 1137.8, 1137.8, 1063.6, 854.3, 695.2.

[0322] [ka]

[0323] [Example 39] Compound (1)-110 (31.1 mg, 50.1 μmol) obtained in Example 30 and compound (2)-101 (dehydroalanine derivative) (22.8 mg, 60.4 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the obtained reaction solution was concentrated under reduced pressure, and the obtained residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 94 / 6 to 77 / 23 (volume ratio)). As described above, as the sugar amide compound (Compound (3)), the compound represented by the following formula (3)-110 was obtained as a colorless solid (yield 34.5 mg, yield 92%).

[0324] That the obtained product was Compound (3)-110 was 1 confirmed by 13 1H NMR, 1 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time are shown below. 13 1H NMR (600 MHz, CD3OD) δ (ppm): 7.39 - 7.33 (m, 5H), 5.60 (m, 1H), 5.18 (s, 2H), 4.93 (d, J = 9.1 Hz, 1H), 3.86 - 3.80 (m, 3H), 3.71 - 3.65 (m, 4H), 3.57 (m, 1H), 3.49 - 3.43 (m, 2H), 3.32 - 3.23 (m, 2H), 2.72 (dt, J = 14.9, 6.0 Hz, 1H), 1.46 (s, 18H). 13 13C NMR (151 MHz, CD3OD) δ (ppm): 171.9, 171.9, 170.2, 170.1, 152.0, 151.9, 135.6, 135.6, 128.2, 127.9, 127.9, 127.9, 101.5, 83.5, 83.4, 79.7, 79.7, 79.6, 77.4, 77.3, 76.8, 73.7, 73.4, 72.8, 72.2, 72.2, 70.1, 66.9, 66.9, 61.3, 60.6, 54.9, 54.7, 36.6, 36.5, 26.8. HRMS (ESI): calculated for C 33 H 50 N2O 17 Na ([M + Na] +): 769.3002, found: 769.3020. IR (ATR, cm- 1 ): 1732.7, 1694.2, 1540.9, 1454.1, 1363.4, 1230.4, 1139.7, 1018.2, 844.9, 699.1.

[0325] [ka]

[0326] [Example 40] Compound (1)-111 (27.8 mg, 25.1 μmol) obtained in Example 31 and compound (2)-101 (dehydroalanine derivative) (11.4 mg, 30.2 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 3DPAFIPN (photo-oxidation-reduction catalyst) (concentration 1.25 mM, 500 μL, 0.625 μmol as photo-oxidation-reduction catalyst) and water (500 μL) were added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction solution was concentrated under reduced pressure, and the resulting residue was purified by two flash silica gel column chromatography cycles (1st cycle mobile phase: chloroform / methanol / water = 24 / 16 / 3 (volume ratio), 2nd cycle mobile phase: chloroform / methanol / water = 12 / 8 / 1 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-111 was obtained as a colorless solid (yield 22.7 mg, yield 90%).

[0327] The obtained compound is compound (3)-111. 1 1H NMR, 13It was confirmed by \(^{13}\)C NMR, HRMS (ESI), and IR. The analytical data obtained at this time are shown below. 1 \(^{1}\)H NMR (600 MHz, D\(_2\)O) δ (ppm): 7.35 - 7.29 (m, 5H), 5.48 (dt, J = 6.9, 2.0 Hz, 1H), 5.33 - 5.30 (m, 4H), 5.15 (dd, J = 12.2, 3.4 Hz, 1H), 5.10 (dd, J = 12.2, 3.1 Hz, 1H), 4.87 (dd, J = 8.9, 8.9 Hz, 1H), 3.90 - 3.84 (m, 3H), 3.80 - 3.71 (m, 12H), 3.70 - 3.66 (m, 2H), 3.63 (m, 1H), 3.60 - 3.52 (m, 9H), 3.50 (dd, J = 9.9, 3.9 Hz, 1H), 3.36 - 3.30 (m, 2H), 3.11 (dt, J = 16.3, 6.6 Hz, 1H), 2.77 (ddd, J = 20.6, 13.5, 7.6 Hz, 1H), 1.33 (s, 18H). 13 \(^{13}\)C NMR (151 MHz, D\(_2\)O) δ (ppm): 173.2, 171.1, 171.1, 152.3, 152.3, 134.9, 128.8, 128.7, 1,28.4, 127.5, 99.7, 99.6, 99.6, 99.4, 99.4, 79.2, 79.1, 77.0, 76.9, 76.,8, 76.7, 76.4, 76.3, 76.0, 73.3, 73.3, 72.8, 72.7, 71.7, 71.7, 71.5, 71.2, 71.1, 71.1, 69.3, 68.0, 60.4, 60.4, 55.2, 55.1, 36.2, 29.6, 27.1. HRMS (ESI): calculated for C 51 H 80 N\(_2\)O 32 Na ([M + Na] + ): 1255.4586, found: 1255.4650. IR (ATR, cm\(^{-1}\)) 1): 1677.8, 1538.9, 1368.3, 1247.7, 1148.4, 1072.2, 1015.3, 846.6, 754.0, 697.1.

[0328] [ka]

[0329] [Example 41] Compound (1)-112 (14.0 mg, 15.0 μmol) obtained in Example 32 and compound (2)-101 (dehydroalanine derivative) (6.8 mg, 18.0 μmol) obtained in Production Example 6 were placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of 4CzIPN (photo-oxidation-reduction catalyst) (concentration 1.25 mM, 61 μL, 0.0763 μmol as photo-oxidation-reduction catalyst) and water (975 μL) were added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (mobile phase: chloroform / methanol = 70 / 30~45 / 55 (volume ratio)). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-112 was obtained as a colorless solid (yield 11.2 mg, yield 77%, S-isomer / R-isomer = 0.83 / 1.0).

[0330] The obtained compound is compound (3)-112. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 1H NMR (600 MHz, CD3OD)δ(ppm): 7.39-7.33 (m, 5H), 5.60 (dd, J = 11.7, 6.2 Hz, 1H), 5.19 (s, 2H), 4.95 (dd, J = 9.1, 2.4 Hz, 1H), 4.47 (d, J = 7.8 Hz, 1H), 4.08 (d, J = 9.1 Hz, 1H), 3.98 (br s, 1H), 3.92-3.85 (m, 4H), 3.82-3.76 (m, 2H), 3.75-3.69 (m, 2H), 3.68-3.57 (m, 6H), 3.53-3.48 (m, 2H), 3.29-3.23 (m, 1H), 2.85 (d, J = 8.5 Hz, 1H), 2.72 (ddd, J = 16.5, 10.4, 6.0 Hz, 1H), 2.03 (s, 3H), 1.79 (t, J = 11.6 Hz, 2H), 1.46 (s, 18H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 174.1, 171.9, 171.8, 170.1, 170.1, 152.0, 151.9, 136.1, 135.6, 135.6, 128.2, 127.9, 127.9, 127.9, 103.7, 100.0, 83.4, 83.4, 79.7, 79.6, 79.2, 76.6, 76.2, 75.9, 75.8, 75.4, 73.5, 72.3, 71.6, 69.4, 68.6, 68.0, 67.9, 66.9, 66.9, 62.9, 61.3, 60.5, 54.9, 54.8, 52.6, 36.6, 36.6, 26.8, 21.3. HRMS (ESI): calculated for C 44 H 67 N3O 25 Na2([M + Na] + ): 1082.3775, found: 1082.3807. IR (ATR, cm- 1): 1734.7, 1692.2, 1606.4, 1551.5, 1368.3, 1228.4, 1135.9, 1070.3, 1025.9, 844.7, 739.6.

[0331] [ka]

[0332] [Example 42] Compound (1)-113 (4.00 mg, 1.74 μmol) obtained in Example 33 was placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of compound (2)-103 (dehydroalanine derivative) obtained in Production Example 8 (concentration 10 mM, 520 μL, 5.20 μmol as compound (2)-103), a THF solution of the aforementioned 4CzIPN (photo-oxidation-reduction catalyst) (concentration 1.25 mM, 35 μL, 0.0438 μmol as photo-oxidation-reduction catalyst), and water (555 μL) were added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was purified by preparative high-performance liquid chromatography (mobile phase flow rate: 3.0 mL / min, linear gradient: 0.1 vol% trifluoroacetic acid aqueous solution / acetonitrile (volume ratio) = 98 / 2~50 / 50 (30 min)). Based on the above, a compound represented by the following formula (3)-113 was obtained as a sugar amide compound (compound (3)) as a light, soft, white solid (yield 2.45 mg, yield 61%).

[0333] The obtained compound is compound (3)-113. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 1 H NMR (600 MHz, D2O)δ(ppm): 7.3-7.33 (m, 5H), 5.13 (s, 2H), 5.05 (s, 1H), 4.97 (t, J = 10.3 Hz, 1H), 4.87 (s, 1H), 4.52 (d, J = 7.7 Hz, 2H), 4.47 (m, 1H), 4.36 (d, J = 7.9 Hz, 2H), 4.17 (s, 1H), 4.11 (m, 1H), 4.03 (m, 1H), 3.93-3.39 (m, 60H), 2.78-2.68 (m, 2H), 2.60-2.57 (m, 2H), 1.98-1.91 (m, 15H), 1.64 (t, J = 12.1 Hz, 2H), 1.30 (s, 9H). 13 C NMR (151 MHz, D2O)δ(ppm): 174.9, 174.9, 174.8, 174.8, 173.3, 172.6, 135.2, 128.8, 128.7, 128.2, 103.5, 100.5, 100.0, 99.6, 99.3, 99.2, 96.9, 81.7, 81.7, 80.7, 80.7, 80.5, 79.4, 79.4, 78.5, 78.4, 78.3, 78.3, 76.4, 76.2, 76.1, 75.3, 74.4, 74.3, 73.7, 73.5, 72.8, 72.5, 72.5, 72.4, 72.1, 72.0, 71.6, 70.9, 70.7, 70.2, 69.4, 68.5, 68.3, 68.1, 67.8, 67.3, 67.3, 65.8, 65.7, 63.3, 62.7, 61.7, 61.6, 61.0, 60.2, 59.9, 59.8, 54.8, 54.6, 53.6, 53.6, 51.8, 39.9, 27.5, 22.4, 22.0. HRMS (ESI): calculated for C 92 H 147 N7O 61 ([M + 2H] 2+ ): 1162.9303, found: 1162.9310. IR (ATR, cm- 1 ): 1636.3, 1558.2, 1374.0, 1307.5, 1036.6, 898.7.

[0334] [ka]

[0335] [Example 43] Compound (1)-101 (23.0 mg, 50.2 μmol) and compound (2)-104 (24.6 mg, 60.1 μmol) obtained in Example 1 were placed in a vial (5 mL capacity). Next, the vial is moved into the glove box, and the Acr + A THF solution of -diOR (photo-oxidation-reduction catalyst) (1.25 mM concentration, 1.0 mL, 1.25 μmol as photo-oxidation-reduction catalyst) was added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was concentrated under reduced pressure, and the resulting residue was purified twice by flash silica gel column chromatography (mobile phase: chloroform / methanol = 95 / 5 to 77 / 23 (volume ratio)). Based on the above, a compound represented by the following formula (3)-114 was obtained as a sugar amide compound (compound (3)) as a pale yellow solid (yield 26.5 mg, yield 86%, S-isomer / R-isomer = 1.6 / 1.0).

[0336] The obtained compound is compound (3)-114. 1 1H NMR, 13 Confirmation was performed using 13C NMR, HRMS (ESI), and IR. The analytical data obtained at this time is shown below. 1H NMR (600 MHz, CD3OD)δ(ppm): 7.31-7.27 (m, 2H), 7.24-7.18 (m, 3H), 4.91 (d, J = 9.1 Hz, 1H) 4.77 (dd, J = 7.9, 5.2 Hz, 0.61H), 4.73 (dd, J = 6.2, 6.2 Hz, 0.39H), 4.67-4.64 (m, 1H), 4.35 (, dd J = 8.5, 6.6 Hz, 0.39H), 4.27 (dd, J = 7.1, 7.1 Hz, 0.61H), 3.83 (ddd, J = 11.9, 9.8, 2.2 Hz, 1H), 3.70 (s, 1.83H), 3.68 (s, 1.17H), 3.68-3.64 (m, 1H), 3.43-3.39 (m, 1H), 3.37-3.33 (m, 1H), 3.32-3.29 (m, 1H), 3.28-3.24 (m, 1H), 3.15 (dt, J = 13.7, 5.6 Hz, 1H), 3.09-3.05 (m, 1H), 2.78-2.72 (m, 1.31H), 2.60 (dd, J = 15.7, 8.0 H, 0.61H), 2.00 (s, 1.17H), 1.98 (s, 1.83H), 1.70-1.66 (m, 1H), 1.60-1.55 (m, 1H), 0.98-0.93 (m, 6H). 13 C NMR (151 MHz, CD3OD)δ(ppm): 173.8, 173.4, 172.3, 171.8, 171.7, 171.9, 171.4, 171.3, 136.7, 136.5, 128.9, 128.9, 128.2, 128.1, 126.5, 126.5, 79.7, 79.6, 78.3, 78.2, 77.5, 77.5, 72.7, 72.7, 70.0, 70.0, 61.3, 61.3, 54.2, 54.1, 52.7, 52.0, 51.4, 51.3, 49.8, 40.0, 39.7, 36.9, 36.9, 36.9, 36.8, 24.5, 24.4, 22.1, 21.9, 21.1, 21.0, 20.7, 20.5. HRMS (ESI): calculated for C 28 H 42 N4O 11 Na ([M + Na] + ): 633.2742, found: 633.2742. IR (ATR, cm- 1 ): 1727.9, 1629.6, 1536.0, 1439.6, 1368.3, 1219.8, 1075.1, 1018.2, 893.8, 697.1.

[0337] [ka]

[0338] [Example 44] Compound (1)-101 (4.01 mg, 3.05 μmol) obtained in Example 1 was placed in a vial (capacity 5 mL). Next, the vial was transferred to a glove box, and a THF solution of the compound represented by formula (2)-105 (cyclosporine derivative) (concentration 10 mM, 915 μL, 9.15 μmol as compound (2)-105), a THF solution of the 4CzIPN (photo-oxidation-reduction catalyst) (concentration 1.25 mM, 61.0 μL, 0.0763 μmol as photo-oxidation-reduction catalyst), and water (975 μL) were added to the vial. The vial was then sealed by attaching a screw cap, removed from the glove box, and the reaction was carried out by stirring the contents at room temperature for 16 hours while irradiating the contents with light using a blue light-emitting diode (Kessil A 160 WE Tuna blue), as in Example 5. Next, the resulting reaction mixture was purified by preparative thin-layer chromatography (mobile phase: chloroform / methanol = 15 / 2 (volume ratio)) and gel filtration chromatography (resin: Sephadex LH-20, mobile phase: methanol). Based on the above, a sugar amide compound (compound (3)) represented by the following formula (3)-115 was obtained as a colorless solid (yield 1.99 mg, yield 43%).

[0339] The obtained compound was confirmed to be compound (3)-115 by HRMS (ESI). The analytical data obtained at this time is shown below. HRMS (ESI): calculated for C 75 H 138 N 12 O 18 SiNa ([M + Na] + ): 1545.9914, found: 1545.9936.

[0340] [ka] [Industrial applicability]

[0341] The present invention can be used as a means for introducing a sugar skeleton into an amino acid derivative, and for producing sugar amide compounds having a structure in which a sugar skeleton has been introduced into an amino acid derivative, and can be used, for example, for the production of glycopeptides or glycoproteins.

Claims

1. The following general formula (1) 【Chemistry 1】 (wherein, R １ is an acetylamino group or a hydroxyl group; R ２ , R ３ , R ４ and R ５ are each independently an alkyl group, an aryl group or an aralkyl group; G １ is a hydrogen atom, a methyl group, or a group represented by the general formula -CH ２ -OX ３ ; X １ , X ２ and X ３ are each independently a hydrogen atom, a monovalent group having a structure in which the anomeric hydroxyl group in a saccharide is removed, or a monovalent group having a structure in which the anomeric hydroxyl group in a substituted saccharide in which one or more hydrogen atoms in the saccharide are substituted with substituents is removed.) A compound represented by the formula.

2. The compound according to claim 1, wherein the sugars are monosaccharides, or oligosaccharides or polysaccharides having a structure in which 2 to 15 monosaccharides are bonded together.

3. The compound according to claim 2, wherein the monosaccharide is glucose, and the oligosaccharide does not have a structure to which a monosaccharide other than glucose is attached, or has a structure to which galactose or sialic acid is attached.

4. The aforementioned R ２ , R ３ , R ４ and R ５ The compound according to any one of claims 1 to 3, wherein each is independently an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms.

5. The aforementioned R ２ and R ５ However, each is independently an alkyl group having 1 to 5 carbon atoms, or an aralkyl group having 7 to 11 carbon atoms. The aforementioned R ３ and R ４ The compound according to claim 4, wherein each is independently an alkyl group having 1 to 5 carbon atoms.

6. The following general formula (11) 【Chemistry 2】 (In the formula, R １ is an acetylamino group or a hydroxyl group; G １ is a hydrogen atom, a methyl group, or a compound of the general formula -CH ２ -OX ３ It is a base represented by X １ , X ２ and X ３ Each of these is independently a monovalent group having a structure in which a hydrogen atom, a hydroxyl group at the anomeric position in a sugar, or a monovalent group having a structure in which one or more hydrogen atoms in the sugar are replaced by substituents, and the hydroxyl group at the anomeric position in a substituted sugar, respectively. Compounds represented by the following general formula (12) 【Transformation 3】 (In the formula, R ２ , R ３ , R ４ and R ５ Each of these is independently an alkyl group, an aryl group, or an aralkyl group; Q １ (This is either a hydroxyl group or a leaving group.) By reacting a compound represented by the following general formula (1) with , the following compound is obtained 【Chemistry 4】 (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , X １ , X ２ and G １ (This is the same as above.) A method for producing a compound represented by [the given formula].

7. The following general formula (1) 【Transformation 5】 (In the formula, R １ R is an acetylamino group or a hydroxyl group; ２ , R ３ , R ４ and R ５ Each of these is independently an alkyl group, an aryl group, or an aralkyl group; G １ is a hydrogen atom, a methyl group, or a compound of the general formula -CH ２ -OX ３ It is a base represented by X １ , X ２ and X ３ Each of these is independently a monovalent group having a structure in which a hydrogen atom, a hydroxyl group at the anomeric position in a sugar, or a monovalent group having a structure in which one or more hydrogen atoms in the sugar are replaced by substituents, and the hydroxyl group at the anomeric position in a substituted sugar, respectively. By irradiating the compound represented by with light, the compound is activated, The activated product of the above compound and the following general formula (2) 【Transformation 6】 (In the formula, R ９ is a hydrogen atom or an alkyl group; Z １ and Z ２ Each of these is independently a hydrogen atom; a protecting group; a monovalent group having a structure in which a hydroxyl group in the carboxyl group has been removed from an amino acid, substituted amino acid, peptide, or protein; or a monovalent group having a structure in which an amino group or substituted amino group has been removed from a peptide or protein, provided that Z １ and Z ２ It is not the case that both are monovalent groups; Z ３ Z is a monovalent group having a structure in which a hydrogen atom in an amino group or substituted amino group has been removed from an amino acid, substituted amino acid, peptide or protein; or a monovalent group having a structure in which a carboxyl group or substituted carboxyl group has been removed from a peptide or protein; and is not a hydrogen atom. １ or Z ２ And, Z ３ (These two elements may be joined together to form a ring.) By reacting a compound represented by with , the following general formula (3) is obtained 【Transformation 7】 (In the formula, R １ , X １ , X ２ G １ , R ９ Z １ Z ２ and Z ３ (This is the same as above.) A method for producing a sugar amide compound, which is represented by [the formula shown].

8. A method for producing a sugar amide compound according to claim 7, comprising activating the compound represented by the general formula (1) by irradiating it with light in the presence of a photocatalyst.

9. The aforementioned photocatalyst is, 【Transformation 8】 A method for producing a sugar amide compound according to claim 8, wherein the compound is one or more selected from the group consisting of compounds represented by .

10. The aforementioned R ９ However, it is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. Said Z ３ A method for producing a sugar amide compound according to any one of claims 7 to 9, wherein the group is an alkoxy group having 1 to 5 carbon atoms; an aryloxy group having 6 to 10 carbon atoms; an aralkyloxy group having 7 to 11 carbon atoms; an amino group; a substituted amino group; a monovalent group having a structure in which a hydrogen atom in an amino group or a substituted amino group has been removed from an amino acid, a substituted amino acid, a peptide, or a protein; or a monovalent group having a structure in which a carboxyl group or a substituted carboxyl group has been removed from a peptide or a protein.

11. The compound represented by the above general formula (2) is given by the following general formula (21) 【Chemistry 9】 (In the formula, R ９ Z １ Z ２ and Z ３ (This is the same as above.) Dehydration reaction in a compound represented by the following general formula (22) 【Chemistry 10】 (In the formula, R ９ Z １ Z ２ and Z ３ (This is the same as above.) A method for producing the sugar amide compound according to claim 7 or 8, obtained by a hydrogen desulfurization reaction in the compound represented by .

12. The aforementioned R ２ , R ３ , R ４ and R ５ The method for producing a sugar amide compound according to claim 7 or 8, wherein each is independently an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 15 carbon atoms, or an aralkyl group having 7 to 16 carbon atoms.

13. The method for producing a sugar amide compound according to claim 7 or 8, wherein the sugars are monosaccharides, or oligosaccharides or polysaccharides having a structure in which 2 to 15 monosaccharides are bonded together.

14. A method for producing a sugar amide compound according to claim 13, wherein the monosaccharide is glucose, and the oligosaccharide does not have a structure to which a monosaccharide other than glucose is attached, or has a structure to which galactose or sialic acid is attached.

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