A kind of polybasic sulfonic acid compound and intermediate and application thereof

Abstract

This invention discloses a polysulfonic acid compound, its intermediates, and its applications. The polysulfonic acid compound of this invention is shown in Formula I-1 or I-2. Under the catalysis of the compounds of this invention, asymmetric hydrogenation alkoxycyclization reactions of unactivated olefin substrates can be achieved.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a polysulfonic acid compound and its applications. Background Technology

[0002] In modern asymmetric organic synthesis, designing practical and environmentally friendly chiral catalysts is crucial for achieving highly enantioselective control to obtain optically pure enantiomeric compounds. In this regard, chiral Brønsted acids derived from chiral (R) or (S)-1,1'-bi-2-naphthol have been widely used as chiral organocatalysts or as chiral ligands for metal catalysis. Compared to common chiral binaphthalene dicarboxylic acids, binaphthalene phosphoric acid, and binaphthalene phosphoramide, chiral (R) or (S)-1,1'-binaphthalene disulfonic acids are stronger Brønsted acids, making binaphthalene di or polysulfonic acids highly promising for asymmetric catalysis. As early as 2008, the Ishihara group reported the first simple synthesis of (R)-1,1'-binaphthalene-2,2'-disulfonic acid, a five-step synthetic method that successfully applied the synthesized disulfonic acid to asymmetric Mannich-type reactions. [1] Subsequently, List and Ishihara's research groups modified the chemoselectivity and enantioselectivity of this simple chiral disulfonic acid by attaching different substituents at the 3 or 6 positions to catalyze different reactions. [2] In addition, these chiral disulfonic acids have been shown to be effective chiral ligands for metal-mediated enantioselective catalysis. [3] Although these chiral disulfonic acids have demonstrated exceptional advantages in asymmetric catalysis, especially exhibiting unique catalytic properties in certain asymmetric catalytic reactions, the limited availability of raw materials, lack of synthetic methods, and low synthesis efficiency have resulted in very few reports on (R) or (S)-1,1'-binaphthyl disulfonic acids over the past decade, limited to the few cases mentioned in the aforementioned literature. Furthermore, chiral binaphthyl polysulfonic acids have not been reported to date.

[0003] [1].Hatano,M.;Maki,T.;Moriyama,K.;Arinobe,M.;Ishihara,K.,J.Am.Chem.Soc.2008,130,16858.

[0004] [2].(a)Garcia-Garcia,P.;Lay,F.;Garcia-Garcia,P.;Rabalakos,C.;List,B.,Angew.Chem.Int.Ed.Engl.2009,48,4363.(b)Hatano,M.;Ozaki,T.;Nishikawa,K.;Ishihar a,K.,J.Org.Chem.2013,78,10405.(c)Satake,S.;Kurihara,T.;Nishikawa,K.;Mochizuki,T.;Hatano,M.;Ishihara,K.;Yoshino,T.;Matsunaga,S.,Nat.Catal.2018,1,585.

[0005] [3].(a)Hatano,M.;Hattori,Y.;Furuya,Y.;Ishihara,K.,Org.Lett.2009,11,2321.(b)Lalonde,RL;Wang,ZJ;Mba,M.;Lackner,AD Toste, FD, Angew. Chem. Int. Ed. Engl. 2010, 49, 598. (c) Hatano, M.; Nishikawa, K.; Ishihara, K., J. Am. Summary of the Invention

[0006] This invention addresses the limitation of existing technologies in the availability of a limited variety of naphthalene-based skeleton compounds as catalysts. To this end, it provides a polysulfonic acid compound, its intermediates, and their applications. The polysulfonic acid compound of this invention can achieve asymmetric hydrogenation alkoxycyclization of unactivated olefin substrates under mild conditions. In particular, when a chiral polysulfonic acid compound is used as a catalyst, it can also prepare such oxygen-containing cyclic compounds with high enantioselectivity.

[0007] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0008] The present invention also provides a compound as shown in formula I-1 or I-2;

[0009]

[0010] Where A1 is C 6-18 The aryl group may be absent (when A1 is absent, there is no substituent on the naphthalene ring, i.e.) (For H);

[0011] A1', A2, and A2' are independently C 6-18 Aryl;

[0012] R 1 and R 7 H and C independently 1-16 Alkyl or adamantyl;

[0013] R 2 and R 2 'Independently hydroxyl or -NR 2a R 2b ;

[0014] R 2a and R 2b Independently for C 1-6 alkyl;

[0015] R 3 and R 3 'Independently for H, C 1-6 Alkyl or -S(O)2NR 3a R 3b ;

[0016] R 3a and R 3b Independently for C 1-6 alkyl;

[0017] R 4 It is -S(O)2OH or a hydroxyl group, or two R groups. 4 Together When R 4 When it is a hydroxyl group, the R... 2 and R 2 ' is a hydroxyl group;

[0018] R 5 R 5 '、R 6 and R 6 'Independently for H, C 1-6 Alkyl or R 5-1 Replacement C 1-6 Alkyl (R) 5-1 The number is one or more (e.g., 1, 2, or 3), and R 5 R 5’ R 6 and R 6 'Not both H;

[0019] R 5-1 C that is halogenated or halogenated 1-6 Alkyl groups (with one or more halogens, such as 1, 2 or 3);

[0020] Furthermore, the compound shown in Formula I-2 is not...

[0021] In a preferred embodiment of the present invention, when A1, A1', A2, and A2' are independently C 6-18 When aryl, the C 6-18 The aryl group is phenyl, naphthyl, phenanthryl or anthracene, preferably phenyl or naphthyl.

[0022] When A1 and A1' are independently phenyl, the R 3 Or R 3 'Preferably located at the para or meta position of the phenyl-naphthalene ring linking site on the phenyl group.'

[0023] When A1 and A1' are independently phenyl, the Preferably, it is located at the meta position of the phenyl group at the phenyl ring linking site.

[0024] When A1 and A1' are independently naphthyl groups, the aforementioned Preferably, it is located at position 8 of the naphthyl group (i.e., position 2 on the naphthyl group with A1 and A1' as the connection sites with the naphthalene ring). Replace positions A1 and A1' at position 8, for example ).

[0025] When A2 and A2' are independently phenyl, the R 5 R 5 '、R 6 Or R 6 'Preferably located at the meta position of the phenyl group at the phenyl ring-naphthalene ring connection site.'

[0026] In a preferred embodiment of the present invention, when R 1 and R 7 Independently for C 1-16 When alkyl, the C 1-16 Alkyl groups are straight-chain C466. 1-16 alkyl or branched C 1-16 Alkyl groups, preferably straight-chain C4 groups 1-16 alkyl.

[0027] When the R 1 and R 7 Independently for linear C 1-16 When alkyl, the straight-chain C 1-16 The alkyl group is preferably n-hexadecyl or n-octyl.

[0028] When the R 1 and R 7 Independent for branch C 1-16 When alkyl, the C of the branched chain 1-16 Alkyl groups are preferably branched C4 groups. 3-6Alkyl group, preferably tert-butyl group.

[0029] In a preferred embodiment of the present invention, when R 2a and R 2b Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl or isopropyl, preferably methyl.

[0030] In a preferred embodiment of the present invention, when R 3 and R 3 'Independently for C 1-6 When alkyl, the C 1-6 The alkyl group can be methyl, ethyl, n-propyl, isopropyl, or n-pentyl, preferably methyl or n-pentyl.

[0031] In a preferred embodiment of the present invention, when R 3a and R 3b Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl or isopropyl, preferably methyl.

[0032] In a preferred embodiment of the present invention, when R 5 R 5 '、R 6 and R 6 'Independently for C 1-6 Alkyl or R 5-1 Replacement C 1-6 When alkyl, the C 1-6 alkyl or the R 5-1 Replacement C 1-6 C in alkyl 1-6 The alkyl group is methyl, ethyl, n-propyl or isopropyl, preferably methyl.

[0033] In a preferred embodiment of the present invention, when R 5-1 C that is halogenated or halogenated 1-6 When alkyl, the halogen or the halogen-substituted C 1-6 The halogen in the alkyl group is F, Cl, Br or I, preferably F.

[0034] In a preferred embodiment of the present invention, when R 5-1 C replaced by halogen 1-6 When alkyl, the halogen-substituted C 1-6 The alkyl group is trifluoromethyl.

[0035] In a preferred embodiment of the present invention, when R 5 R 5 '、R 6 and R6 'Independently for R 5-1 Replacement C 1-6 When alkyl, the R 5-1 Replacement C 1-6 The alkyl group is trifluoromethyl or -CF(CF3)2.

[0036] In a preferred embodiment of the present invention, the general formula of the compound represented by formula I-1 is:

[0037]

[0038] In a preferred embodiment of the present invention, the general formula of the compound shown in Formula I-2 is:

[0039]

[0040] In a preferred embodiment of the present invention, the general formula of the compound represented by formula I-1 is shown as I-1a, I-1b, I-1c or I-1d:

[0041]

[0042] In a preferred embodiment of the present invention, A1 is C. 6-18 Aryl.

[0043] In a preferred embodiment of the present invention, R 1 and R 7 Independently for C 1-16 Alkyl or adamantyl.

[0044] In a preferred embodiment of the present invention, R 2 and R 2 'for -NR 2a R 2b .

[0045] In a preferred embodiment of the present invention, R 3 and R 3 'Independently for C 1-6 Alkyl or -S(O)2NR 3a R 3b .

[0046] In a preferred embodiment of the present invention, R 4 It is -S(O)2OH.

[0047] In a preferred embodiment of the present invention, R 5 R 5 '、R 6 and R 6 'Independently for R 5-1 Replacement C 1-6 alkyl.

[0048] In a preferred embodiment of the present invention Independently

[0049] In a preferred embodiment of the present invention Independently

[0050] In a preferred embodiment of the present invention for (For example ), (For example ), (For example ), (For example ), (For example ), (For example ), (For example )or (For example ).

[0051] In a preferred embodiment of the present invention, the compound represented by formula I-1:

[0052] A1 is C 6-18 Aryl;

[0053] When A1' is C 6-18 Aryl, the C 6-18 When the aryl group is naphthyl, the R... 1 C 1-16 Alkyl or adamantyl; the R 2 'for -NR 2a R 2b ;

[0054] When R 4 When it is a hydroxyl group, the R... 3 and R 3 'For H.

[0055] In a preferred embodiment of the present invention, the compound represented by formula I-1:

[0056] A1 is C 6-18 Aryl;

[0057] R 1 For H or C 1-16 alkyl;

[0058] R 3 For H or C1-6 alkyl;

[0059] R 4 It is -S(O)2OH or hydroxyl group;

[0060] When R 2 and R 2 Independently for -NR 2a R 2b At that time, the R mentioned 1 C 1-16 alkyl;

[0061] When R 2 and R 2 When it is independently a hydroxyl group, the R... 1 For H;

[0062] When R 2 and R 2 'Independently a hydroxyl group, R 4 When it is -S(O)2OH, A1 and A1' are independently C 6-18 Aryl, the C 6-18 The aryl group is naphthyl.

[0063] In a preferred embodiment of the present invention, the compound represented by formula I-1:

[0064] A1 is C 6-18 Aryl; the C 6-18 The aryl group is phenyl;

[0065] R 1 C 1-16 Alkyl or adamantyl;

[0066] R 2 and R 2 'for -NR 2a R 2b ;

[0067] R 3 and R 3 'For C 1-6 alkyl;

[0068] R 4 It is -S(O)2OH.

[0069] In a preferred embodiment of the present invention, the compound represented by Formula I-1 is any one of the following compounds and / or its isomers:

[0070]

[0071]

[0072] The compound represented by Formula I-2 is any of the following compounds and / or its isomers:

[0073]

[0074] The present invention provides a method for preparing the compounds shown in formula I-1 or I-2 as described above, which is method 1, 2, 3 or 4 as follows:

[0075] Method 1:

[0076] When R 4 When the form is -S(O)2OH, the preparation method of the compound shown in Formula I-1 includes the following steps: under acidic reagent, compound II-a is subjected to an acidification reaction in a solvent as shown in the following formula to obtain the compound shown in Formula I-1;

[0077]

[0078] Where Z and Z' are independently hydroxyl groups or -SO3M 1a M 1a Independently Na or K; R 13 and R 13‘ Independently -ONa, -OK, or -NR 2a R 2b ;R 2a and R 2b The definitions are as described above;

[0079] Method 2:

[0080] When R 4 When OH, the preparation method of the compound shown in Formula I-1 includes the following steps: in the presence of an acidic reagent or BBr3, compound II-b is subjected to a deprotection reaction in a solvent as shown in the following formula to obtain the compound shown in Formula I-1;

[0081]

[0082] Among them, R 15 and R 15’ Independently a hydroxyl protecting group or C 1-3 Alkyl; M 2a and M 2b Independently Na or K;

[0083] Method 3:

[0084] When two R 4 Together The method for preparing the compound as shown in Formula I-1 includes the following steps:

[0085] Step (1): The compound I-1 obtained in method 2 and phosphorus oxychloride are subjected to esterification reaction in a solvent to obtain a mixed solution;

[0086] Step (2): The mixed solution obtained in step (1) is subjected to a hydrolysis reaction in water to obtain the compound of formula I-1;

[0087]

[0088] Method 4:

[0089] When R 4 When the compound is -S(O)2OH, the preparation method of the compound shown in formula I-1 or I-2 includes the following steps: in the presence of an oxidant and formic acid, compound II-d is oxidized in a solvent according to the following formula to obtain the compound shown in formula I-1 or I-2.

[0090]

[0091] Among them, R 16a and R 16b Independently for C 1-3 alkyl;

[0092] R 18 For R 3 R 18a -S(O2)R 2 Or, R 18 For R 5 R 18a For R 6 ;

[0093] R 19 -S(O2)R 2’ R 19a For R 3’ Or, R 19 For R 6’ R 19a For R 5’ ;

[0094] R 2 R 2’ R 3 R 3’ R 5 R 5’ R 6 and R 6’ The definitions are the same as those described above.

[0095] In Method 1, the conditions and operations of the acidification reaction can be the conventional conditions and operations for this type of acidification reaction in the art. The present invention particularly prefers the following conditions and operations:

[0096] In Method 1, the acidification reaction is carried out on a cation exchange resin (e.g., Amberlyst 15) (e.g., using an alcohol solvent (e.g., methanol) as an eluent).

[0097] In Method 2, the conditions and operations for the deprotection reaction can be the conventional conditions and operations for this type of reaction in the art.

[0098] When the deprotection reaction is carried out in the presence of an acidic reagent, the present invention particularly prefers the following conditions and operations:

[0099] The acidic reagent can be hydrochloric acid (e.g., 12 mol / L hydrochloric acid).

[0100] The molar ratio of the acidic reagent to the compound II-b can be 5:1 to 25:1 (e.g., 10:1).

[0101] The solvent can be an ether solvent (e.g., dioxane).

[0102] The temperature of the deprotection reaction can be 30-80℃ (e.g., 60℃).

[0103] When the deprotection reaction is carried out in the presence of BBr3, the present invention particularly prefers the following conditions and operations:

[0104] The acidic reagent can be hydrochloric acid (e.g., 12 mol / L hydrochloric acid).

[0105] The molar ratio of BBr3 to compound II-b can be 5:1 to 25:1 (e.g., 10:1).

[0106] The solvent can be a halogenated hydrocarbon solvent (e.g., dichloromethane).

[0107] The temperature for the deprotection reaction can be -78 to 60°C (e.g., -78°C).

[0108] In Method 2, the progress of the deprotection reaction can be monitored using methods conventional in the art (e.g., TLC, LC-MS). In this invention, the endpoint is defined as the cessation or disappearance of compound II-b. The deprotection reaction takes 2-16 hours (e.g., 5 hours).

[0109] In Method 3, the conditions and operations of the esterification reaction can be conventional conditions and operations for this type of reaction in the art. The present invention particularly prefers the following conditions and operations:

[0110] In method 3, the solvent can be pyridine.

[0111] In method 3, the molar ratio of phosphorus oxychloride to compound I-1 can be 1:1 to 6:1 (e.g., 4:1).

[0112] In Method 3, the temperature of the esterification reaction can be 50-110°C (e.g., 95°C).

[0113] In Method 3, the conditions and operations of the esterification reaction can be the conventional conditions and operations for this type of reaction in the art, such as hydrolysis at 100°C for 4 hours.

[0114] In method 4, the conditions and operations of the oxidation reaction can be conventional conditions and operations for this type of reaction in the art. The present invention particularly prefers the following conditions and operations:

[0115] In method 4, the oxidant can be hydrogen peroxide.

[0116] In method 4, the molar ratio of the oxidant to the compound II-d can be 1:1 to 3:1 (e.g., 1.3:1).

[0117] In method 4, the solvent can be a chlorinated hydrocarbon solvent (e.g., dichloromethane).

[0118] In Method 4, the preparation method of the compound of formula I-1 or formula I-2 may further include the following step: at 280-300℃, compound III-d is subjected to a rearrangement reaction to obtain compound II-d;

[0119]

[0120] The conditions for the rearrangement reaction can be those conventional for such reactions in the art, such as reacting under a protective gas (e.g., nitrogen) or reacting at 290°C for 45 minutes.

[0121] In Method 4, the preparation method of the compound of formula I-1 or formula I-2 may further include the following step: reacting compound IV-d and compound Vd in a solvent in the presence of an alkaline reagent to obtain the compound III-d;

[0122]

[0123] The alkaline reagent can be NaH. The solvent can be an amide solvent (e.g., N,N-dimethylformamide). The reaction temperature can be 50-100℃ (e.g., 85℃).

[0124] The present invention provides the use of the compounds shown above, such as those of formula I-1 and / or I-2, as catalysts in the preparation of compound B;

[0125] The preparation method of compound B includes the following steps: in the presence of the compound as shown in formula I-1 and / or I-2 and the titanium salt, compound A is subjected to a cyclization reaction in a solvent as follows to obtain compound B;

[0126]

[0127] Among them, R 8 R 9 R 10 and R 11 Independent of H, halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, cyano, -C(=O)OR 8-1 C 3-6 cycloalkyl, C 6-18 Aryl or R 8-2 Replacement C 6-18 Aryl (R) 8-1 The number can be one or more, such as 1, 2 or 3);

[0128] R 8-1 C 1-6 alkyl;

[0129] R 8-2 C 2-6 alkenyl or hydroxyl groups;

[0130] Or, R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 3-6 cycloalkyl, C 6-18 aryl or

[0131] R 12 and R 13 H and C independently 1-6 Alkyl or C 6-18 Aryl, or R 12 and R 13 Together with the carbon atom it is attached to, they form C 3-6 cycloalkyl;

[0132] n is 1, 2, or 3.

[0133] In a preferred embodiment of the present invention, when R 8 R 9 R 10 and R 11 Independently for C 1-6 Alkyl or -OC 1-6When alkyl, the C 1-6 Alkyl or -OC 1-6 C in alkyl 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, such as methyl.

[0134] In a preferred embodiment of the present invention, when R 8 R 9 R 10 and R 11 Independently for C 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, such as cyclohexyl.

[0135] In a preferred embodiment of the present invention, when R 8 R 9 R 10 and R 11 Independently for C 6-18 Aryl or R 8-1 Replacement C 6-18 When aryl, the C 6-18 aryl or the R 8-1 Replacement C 6-18 C in aryl 6-18 The aryl group is phenyl, naphthyl, phenanthryl or anthracene, preferably phenyl.

[0136] In a preferred embodiment of the present invention, when R 8-1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, such as methyl.

[0137] In a preferred embodiment of the present invention, when R 8-2 C 2-6 When alkenyl, the C 2-6 The alkenyl group is vinyl or propenyl, and further...

[0138] In a preferred embodiment of the present invention, when R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, such as cyclohexyl.

[0139] In a preferred embodiment of the present invention, when R 8 R 9 R 10 and R11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 6-18 When aryl, the C 6-18 The aryl group is phenyl, naphthyl, phenanthryl, or anthracene, for example, phenyl (i.e., in compound A). For example, naphthyl group ).

[0140] In a preferred embodiment of the present invention, when R 12 and R 13 Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, such as methyl.

[0141] In a preferred embodiment of the present invention, when R 12 and R 13 Independently for C 6-18 When aryl, the C 6-18 The aryl group is phenyl, naphthyl, phenanthryl or anthracene, for example phenyl.

[0142] In a preferred embodiment of the present invention, when R 12 and R 13 Together with the carbon atom it is attached to, they form C 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, such as cyclohexyl.

[0143] In a preferred embodiment of the present invention, compound A is...

[0144] In a preferred embodiment of the present invention, when the compound represented by formula I-1 or I-2 is When; the compound B is

[0145] In a preferred embodiment of the present invention, when the compound represented by formula I-1 or I-2 is When; the compound B is

[0146] The conditions and procedures for the cyclization reaction described herein can be those conventional for such reactions in the art, but the present invention particularly prefers the following conditions and procedures:

[0147] In the cyclization reaction, the organic solvent is preferably one or more of alkane solvents (e.g., cyclohexane), aromatic solvents (e.g., toluene), and halogenated hydrocarbon solvents (e.g., 1,2-dichloroethane).

[0148] In the cyclization reaction, the molar concentration of compound A in the organic solvent can be 0.005-1 mol / L.

[0149] In the cyclization reaction, the titanium salt is preferably one or more of titanium tetramethanol, titanium tetraisopropoxide, titanium tetratert-butoxide, titanium tetraisobutoxide, titanium tetrachloride, titanium triisopropoxide chloride, and titanium isooctyl alcohol, such as titanium isooctyl alcohol.

[0150] In the cyclization reaction, the molar ratio of the titanium salt to the compound of formula A can be 0.02:1 to 0.2:1 (e.g., 0.1:1).

[0151] In the cyclization reaction, the molar ratio of the compound represented by formula I-1 and / or I-2 to the compound of formula A is preferably 0.02:1 to 0.2:1 (e.g., 0.05:1).

[0152] The preferred reaction temperature for the cyclization reaction is 40-200℃, for example, 70-90℃.

[0153] The cyclization reaction can be monitored using conventional monitoring methods in the art (such as TLC, HPLC, or NMR). The present invention uses the point at which the compound of formula A ceases to react as the reaction endpoint. The preferred cyclization reaction time is 20-26 hours, for example, 24 hours.

[0154] The post-treatment of the cyclization reaction can be a conventional post-treatment for such reactions in the art, such as post-treatment using column chromatography (eluent: petroleum ether: ethyl acetate = 50:1).

[0155] The present invention also provides a catalyst composition comprising the compounds shown in Formula I-1 and / or I-2 above and a titanium salt.

[0156] In the catalyst composition, the titanium salt is preferably one or more of titanium tetramethanol, titanium tetraisopropoxide, titanium tetratert-butoxide, titanium tetraisobutoxide, titanium tetrachloride, titanium triisopropoxide chloride, and titanium isooctanol, such as titanium isooctanol.

[0157] The present invention also provides the use of the above-described catalyst composition as a catalyst in the preparation of the above-described compound B;

[0158] The preparation method of compound B includes the following steps: in the presence of the compound as shown in formula I-1 and / or I-2 and the titanium salt, compound A is subjected to a cyclization reaction in a solvent as follows to obtain compound B;

[0159]

[0160] The conditions and procedures for preparing compound B are the same as described above.

[0161] The present invention also provides the above-described compound II-a, compound II-b, compound II-d, compound III-d, or compound IV-d:

[0162]

[0163] Wherein, the compound IV-d is not

[0164] In a preferred embodiment of the present invention, compound II-a, compound II-b, compound II-d, compound III-d, or compound IV-d have the following general formula:

[0165]

[0166] In a preferred embodiment of the present invention, compound II-a, compound II-b, compound II-d, compound III-d, or compound IV-d is any one of the following compounds and / or its isomers:

[0167]

[0168]

[0169]

[0170]

[0171]

[0172] In this invention, the compound "compound" as shown in Formula I-1 or I-2 may have one or more chiral carbon atoms, thus allowing for the isolation of optically pure isomers, such as pure enantiomers, racemates, or mixed isomers. Pure single isomers can be obtained by separation methods in the art, such as chiral crystallization into salts or separation using chiral preparative columns.

[0173] In this invention, the compounds represented by formula I-1 or I-2, if they contain stereoisomers, may exist as a single stereoisomer or a mixture thereof (e.g., a racemic mixture). The term "stereoisomer" refers to cis-trans isomers or optical isomers. These stereoisomers can be separated, purified, and enriched by asymmetric synthesis methods or chiral separation methods (including but not limited to thin-layer chromatography, rotational chromatography, column chromatography, gas chromatography, high-performance liquid chromatography, etc.), and can also be obtained through chiral resolution by bonding (chemical bonding, etc.) or salt formation (physical bonding, etc.) with other chiral compounds. The term "single stereoisomer" means that the mass content of one stereoisomer of the compound is not less than 95% relative to all stereoisomers of the compound.

[0174] The term "alkyl" refers to an alkyl group having a specified number of carbon atoms (e.g., C1-C1). 16 Alkyl groups are straight-chain or branched alkyl groups. Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, etc.

[0175] The term "cycloalkyl" refers to a saturated monocyclic cyclic group consisting only of carbon atoms and having a specified number of carbon atoms (e.g., C3 to C6). Cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0176] The term "aryl" refers to an aryl group having a specified number of carbon atoms (e.g., C6 to C5). 10 An aryl group is a cyclic group consisting solely of carbon atoms, which may be monocyclic or polycyclic, and at least one ring is aromatic (conforming to Hückel's rule). An aryl group is linked to other segments of the molecule via an aromatic or non-aromatic ring. Aryl groups include, but are not limited to, phenyl and naphthyl groups.

[0177] In structural fragments This refers to the connection between this structural segment and other segments in the molecule through this site. For example, It refers to cyclohexyl.

[0178] The term "multiple" refers to 2, 3, 4, or 5.

[0179] The term "alkenyl" refers to a straight-chain or branched hydrocarbon group ("C2-C") having 2-10 carbon atoms, one or more carbon-carbon double bonds, and no carbon-carbon triple bonds. 20 "Alkenyl". The one or more carbon-carbon double bonds can be internal (e.g., in 2-butenyl) or terminal (e.g., in 1-butenyl).

[0180] The term "hydroxyl protecting group" is well known in the art and includes those described in detail in *Protecting Groups in Organic Synthesis*, TW Greene and PGMWuts, 3rd Edition, John Wiley & Sons, 1999, which are incorporated herein by reference. Exemplary hydroxyl protecting groups include, but are not limited to, methyl, methoxymethyl (MOM), methylthiomethyl (MTM), (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacol methyl (GUM), tert-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2- (Trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 4-methoxytetrahydropyranyl (MTHP), 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, 2-(phenylhydroselenoyl)ethyl, tert-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p-methoxy Benzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylhexylsilyl, tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylyl Silyl esters, triphenylsilyl esters, diphenylmethylsilyl esters (DPMS), tert-butylmethoxyphenylsilyl esters (TBMPS), formate esters, 9-fluorenylmethyl carbonate (Fmoc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(benzenesulfonyl)ethyl carbonate (Psec), 2-(triphenylphospho)ethyl carbonate (Peoc), sulfate esters, mesylate esters, benzyl sulfonates, and toluenesulfonates (Ts).

[0181] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0182] The reagents and raw materials used in this invention are all commercially available.

[0183] The positive and progressive effects of this invention are as follows: the polysulfonic acid compounds of this invention can realize the asymmetric hydrogenation alkoxycyclization reaction of unactivated alkenes under mild conditions, and especially when a chiral polysulfonic acid compound is used as a catalyst, such oxygen-containing cyclic compounds can also be prepared with high enantioselectivity. Detailed Implementation

[0184] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0185] Example 1

[0186] This embodiment describes the preparation method of compound 15, which consists of two steps. The synthetic route is as follows:

[0187]

[0188] Includes the following steps:

[0189] (1.1) Step 1:

[0190] Preferably, the reaction conditions for the amination of route a are as follows: A tetrahydrofuran solution of dimethylamine (2.0 equivalents) is added to a round-bottom flask of suitable capacity (the added volume makes the molar concentration of compound 13 of formula 13 1.0 mol / L). Then, brominated benzenesulfonyl chloride compound of formula 13 (1.0 equivalents), triethylamine (1.1 equivalents), and 4-dimethylaminopyridine (0.2 equivalents) are added sequentially, and the mixture is stirred at room temperature for 12 hours. The reaction is analyzed by thin-layer chromatography to determine if it has proceeded completely. Subsequently, the reaction is quenched with 1M hydrochloric acid solution, extracted three times with ethyl acetate, and the resulting organic phase is washed once with saturated brine. After drying with anhydrous sodium sulfate, the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the corresponding brominated benzenesulfonamide products of formulas 14a-f.

[0191] Preferably, the reaction conditions for esterification via route b are as follows: A tetrahydrofuran solution of sodium hydride (1.1 equivalents) is added to a round-bottom flask of suitable capacity (the added volume makes the molar concentration of compound 13 2.2 mol / L). After cooling to 0°C, ethanol (1.0 equivalents) is slowly added, and the mixture is heated to room temperature and stirred for 1 hour. The mixture is then cooled to 0°C, and bromobenzenesulfonyl chloride compound 13 (1.1 equivalents) is slowly added, and the mixture is stirred at 0°C for 2 hours. After the reaction is complete, the mixture is quenched with water, extracted three times with ethyl acetate, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the corresponding ethyl bromide sulfonate product, formula 14g-i.

[0192] Synthesis of compound 14a

[0193]

[0194] By using preferred route a amination reaction conditions, compound 14a (greater than 99% yield) of brominated benzenesulfonyl chloride of formula 13a was given. f =0.32 (PE / EA = 30 / 1). 1 H NMR (400MHz, CDCl3) δ7.98(d,J=2.2Hz,1H),7.54(dd,J=8.2,2.2Hz,1H),7.17(d,J=8.2Hz,1H),2.79(s,6H),2.53(s,3H). 13 C NMR(101MHz, CDCl3)δ137.8,136.9,135.6,134.4,132.5,119.5,37.1,20.2.IR(neat)3084,2933,1463,1318,1136,1059,960,821,739,582,489cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C9H 13 BrNO2S + 277.9845, measured value 277.9837.

[0195] Synthesis of compound 14b

[0196]

[0197] By using preferred route a amination reaction conditions, compound 14b, a white solid, was obtained from brominated benzenesulfonyl chloride compound 13b (yield greater than 99%). f =0.36 (PE / EA = 10 / 1). 1 H NMR (500MHz, CDCl3) δ7.91 (s, 1H), 7.77–7.70 (dd, J = 7.7Hz, 2H), 7.47 (t, J = 7.5Hz, 1H), 2.74 (s, 6H). 13 C NMR(126MHz, CDCl3)δ137.1,135.4,130.4,130.0,125.9,122.7,37.5.IR(neat)2970,1570,1461,1339,1167,953,777,679,584,475cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C8H11 BrNO2S + 263.9689, measured value 263.9675.

[0198] Synthesis of compound 14c

[0199]

[0200] By using preferred amination reaction conditions, brominated benzenesulfonyl chloride compound 13c was given as a colorless liquid compound 14c (greater than 99% yield). f =0.48 (PE / EA = 30 / 1). 1 H NMR(400MHz, CDCl3) δ7.99(d,J=2.1Hz,1H),7.59(dd,J=8.3,2.2Hz,1H),7.24(d,J=8.3Hz,1H),2.9 5–2.86(m,2H),2.81(s,6H),1.67–1.55(m,2H),1.40–1.23(m,4H),0.87(t,J=12.6,8.9,7.9Hz,3H). 13 C NMR(101MHz, CDCl3)δ142.2,137.6,135.7,133.5,132.6,119.4,37.2,32.9,32.1,31.4,27.0,22.6,14.1.HRMS(APCI+)m / z:[M+H] + Calculated value C 13 H 21 BrNO2S + 334.0471, measured value 334.0454.

[0201] Synthesis of compound 14d

[0202]

[0203] By using the preferred route a-amine reaction conditions, compound 13d of brominated benzenesulfonyl chloride was given as a white solid compound 14d (92% yield). f =0.25 (PE / EA = 10 / 1). 1 H NMR (500MHz, CDCl3) δ8.93 (s, 1H), 8.21 (d, J = 7.3Hz, 1H), 8.03 (d, J = 8.2Hz, 1H), 7. 79(d,J=8.7Hz,1H),7.67(d,J=8.8,1.9Hz,1H),7.57(t,J=7.8Hz,1H),2.82(s,6H). 13C NMR(126MHz, CDCl3)δ134.0,132.6,132.0,131.0,130.3,130.1,129.9,127.6,124.5,122.7,37.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 12 H 13 BrNO2S + 313.9845, measured value 313.9845.

[0204] Synthesis of compound of formula 14e

[0205]

[0206] The synthesis of compound 14e differs from that of the amination reaction in the aforementioned route a. In this step, diethylamine (2.0 equivalents) is used instead of dimethylamine (2.0 equivalents) in the aforementioned synthetic route, while the remaining operations and equivalents remain unchanged. Compound 14e (93% yield) is obtained as a white solid from the brominated benzenesulfonyl chloride compound of formula 13a. f =0.33 (PE / EA = 30 / 1). 1 H NMR (400MHz, CDCl3) δ8.01(d,J=2.2Hz,1H),7.51(dd,J=8.1,2.2Hz,1H),7.15(d,J=8.1Hz,1H),3.30(q,J=7.2Hz,4H),2.51(s,3H),1.12(t,J=7.2Hz,6H). 13 C NMR(101MHz, CDCl3)δ140.4,136.5,135.3,134.3,132.1,119.4,41.0,19.9,13.8.HRMS(ESI+)m / z:[M+H] + Calculated value C 11 H 17 BrNO2S + 306.0158, measured value 306.0156.

[0207] Synthesis of compound 14f

[0208]

[0209] The synthesis of compound 14f differs from that of the amination reaction in the aforementioned route a. In this step, 4.0 equivalents of dimethylamine are used instead of the 2.0 equivalents used in the aforementioned route; all other operations or equivalents remain unchanged. Compound 14f (70% yield) is obtained as a white solid from compound 13f of brominated benzenesulfonyl chloride. f= 0.54 (DCM). 1 HNMR(500MHz, CDCl3)δ8.08(s,2H),8.02(s,1H),2.76(s,12H). 13 C NMR(126MHz, CDCl3)δ139.3,134.0,125.0,124.2,37.9.HRMS(ESI+)m / z:[M+H] + Calculated value C 10 H 16 BrN2O4S2 + 370.9730, measured value 370.9720.

[0210] Synthesis of compound of formula 14g

[0211]

[0212] By using the preferred route b esterification reaction conditions, 14 g of a white solid compound of formula 13a was obtained from the benzenesulfonyl chloride bromide. f =0.20 (PE / EA = 30 / 1). 1 H NMR (400MHz, CDCl3) δ8.07(d,J=2.2Hz,1H),7.60(dd,J=8.2,2.2Hz,1H),7.22(d,J=8.2Hz,1H),4.10(q,J=7.1Hz,2H),2.56(s,3H),1.30(t,J=7.1Hz,3H). 13 C NMR(101MHz, CDCl3)δ137.2,136.5,136.4,134.2,132.4,119.5,67.4,19.7,14.8.HRMS(ESI+)m / z:[M+H] + Calculated value C9H 12 BrO3S + 278.9686, measured value 278.9686.

[0213] Synthesis of compound of formula 14h

[0214]

[0215] By using the preferred route b esterification reaction conditions, a colorless liquid compound 14h (87% yield) was obtained from brominated benzenesulfonyl chloride compound of formula 13b. f =0.48 (PE / EA = 10 / 1). 1H NMR (500MHz, CDCl3) δ8.05 (s, 1H), 7.85 (d, J = 7.9Hz, 1H), 7.79 (d, J = 7.3Hz, 1H), 7.46 (t, J = 8.0Hz, 1H), 4.17 (q, J = 7.1Hz, 2H), 1.34 (t, J = 7.2Hz, 3H). 13 C NMR(126MHz, CDCl3)δ137.9,136.6,130.6,130.5,126.2,123.0,67.4,14.6.HRMS(ESI+)m / z:[M+H] + Calculated value C8H 10 BrO3S + 264.9529, measured value 264.9524.

[0216] Synthesis of compound 14i

[0217]

[0218] By using the preferred route b esterification reaction conditions, compound 14i (82% yield) of brominated benzenesulfonyl chloride of formula 13d was given as a white solid. f =0.20 (PE / EA = 10 / 1). 1 H NMR (500MHz, CDCl3) δ8.79(s,1H),8.29(d,J=7.4Hz,1H),8.09(d,J=8.3Hz,1H),7.81(d,J=8.7Hz,1H),7.70(dd ,J=8.8,1.9Hz,1H),7.58(t,J=7.8Hz,1H),4.11(q,J=7.1Hz,2H),1.28(t,J=7.1Hz,3H).HRMS(ESI+)m / z:[M+H] + Calculated value C 12 H 12 BrO3S + 314.9686, measured value 314.9677.

[0219] (1.2) Step 2:

[0220] Preferably, the borate esterification reaction conditions in routes a and b are the same, specifically as follows: Under nitrogen protection, the brominated sulfonamide compound or ethyl sulfonate compound of formula 14 (1.0 equivalent) obtained in step 1 is dissolved in tetrahydrofuran (0.65 mol / L) in a round-bottom flask of appropriate capacity, and then the temperature is lowered to -78°C. n-Butyllithium (1.2 equivalent) is slowly added dropwise to the above reaction solution. After the addition is complete, the mixture is stirred at -78°C for 1.5 hours. Then, isopropanol pinaborate ester (3.0 equivalent) is slowly added. After the addition is complete, the temperature is slowly raised to room temperature and stirred at room temperature for 12 hours. After the reaction is complete, the reaction is quenched with saturated ammonium chloride aqueous solution, and the mixture is extracted three times with diethyl ether. The extracted diethyl ether solution is washed once with water and once with saturated brine, dried over anhydrous magnesium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the respective borate ester products of formula 15.

[0221] Synthesis of compound 15a

[0222]

[0223] By using preferred borate esterification reaction conditions, compound 15a (99% yield) was obtained from sulfonamide compound 14a as a white solid. f =0.32 (PE / EA = 30 / 1). 1 H NMR (400MHz, CDCl3) δ8.28(d,J=1.3Hz,1H),7.84(dd,J=7.5,1.3Hz,1H),7.30(d,J=7.5Hz,1H),2.79(s,6H),2.62(s,3H),1.32(s,12H). 13 C NMR(101MHz, CDCl3)δ141.2,139.0,136.3,135.6,133.6,132.3,84.3,37.2,25.0,21.0.IR(neat)2978,1316,1275,1138,965,851,719,668,555cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C 15 H 25 BNO4S + 326.1592, measured value 326.1590.

[0224] Synthesis of compound 15b

[0225]

[0226] By using preferred borate esterification reaction conditions, compound 15b (99% yield) was obtained from sulfonamide compound 14b as a white solid. f =0.36 (PE / EA = 10 / 1). 1 H NMR (400MHz, CDCl3) δ8.20(s,1H),8.03(d,J=7.4,1.3Hz,1H),7.86(d,J=8.0,1.6Hz,1H),7.55(t,J=2.7Hz,1H),2.72(s,6H),1.35(s,12H). 13 C NMR(101MHz, CDCl3)δ138.9,135.0,133.7,131.6,130.2,128.3,84.4,38.0,24.9.IR(neat)2977,1335,1142,956,749,584cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C 14 H 23 BNO4S + 312.1436, measured value 312.1433.

[0227] Synthesis of compound 15c

[0228]

[0229] By using preferred borate esterification reaction conditions, a colorless liquid compound 15c (99% yield) was obtained from sulfonamide compound of formula 14c. f =0.48 (PE / EA = 30 / 1). 1 H NMR (500MHz, CDCl3) δ8.27(d,J=1.4Hz,1H),7.87(dd,J=7.6,1.3Hz,1H),7.35(d,J=7.6Hz,1H),3 .00–2.93(m,2H),2.78(s,6H),1.67–1.57(m,2H),1.42–1.33(m,3H),1.32(s,12H),0.87(t,3H). 13 C NMR(126MHz, CDCl3)δ146.3,138.9,136.4,135.2,131.3,84.2,37.1,33.5,32.1,31.4,27.0,24.9,22.6,14.1.HRMS(ESI+)m / z:[M+H] + Calculated value C 19 H 33 BNO4S +382.2218, measured value 382.2214.

[0230] Synthesis of Formula 15d compound

[0231]

[0232] By using preferred borate esterification reaction conditions, compound 15d (99% yield) was obtained from sulfonamide compound formula 14d as a white solid. f =0.25 (PE / EA = 10 / 1). 1 H NMR(500MHz, CDCl3)δ9.19(s,1H),8.20(d,J=7.3,1.2Hz,1H),8.03(d,J=8.3Hz,1H),7.93 (d,J=8.2Hz,1H),7.88(d,J=8.2Hz,1H),7.55(t,J=7.8Hz,1H),2.84(s,6H),1.36(s,12H). 13 C NMR(126MHz, CDCl3)δ139.9,134.1,133.8,133.0,130.9,129.7,129.5,126.6,124.5,124.1,75.1,37.5,24.9.HRMS(ESI+)m / z:[M+H] + Calculated value C 18 H 25 BNO4S + 362.1592, measured value 362.1589.

[0233] Synthesis of compound 15e

[0234]

[0235] By using preferred borate esterification reaction conditions, sulfonamide compound 14e was given as a pale yellow solid compound 15e (99% yield). f =0.33 (PE / EA = 30 / 1). 1 H NMR (500MHz, CDCl3) δ8.32(s,1H),7.83(d,J=7.5Hz,1H),7.28(d,J=7.4Hz,1H) ,3.32(q,J=7.4Hz,4H),2.61(s,3H),1.34(s,12H),1.13(t,J=8.2,5.8Hz,6H). 13 C NMR (126MHz, CDCl3) δ140.9,138.8,138.2,135.8,132.2,131.7,84.3,40.8,25.0,20.7,13.8.11 B NMR(160MHz,CDCl3)δ30.8.HRMS(ESI+)m / z:[M+H] + Calculated value C 17 H 29 BNO4S + 354.1905, measured value 354.1903.

[0236] Synthesis of compound 15f

[0237]

[0238] By using preferred borate esterification reaction conditions, solid compound 15f was obtained from sulfonamide compound 14f (99% yield). 1 H NMR (400MHz, CDCl3) δ8.37 (d, J = 1.9 Hz, 2H), 8.22 (t, J = 1.9 Hz, 1H), 2.76 (s, 12H), 1.36 (s, 12H). 13 C NMR(126MHz, CDCl3)δ137.3,134.0,129.0,126.3,85.1,38.1,25.0.HRMS(ESI+)m / z:[M+H] + Calculated value C 16 H 28 BN2O6S2 + 419.1477, measured value 419.1476.

[0239] Synthesis of compound of formula 15g

[0240]

[0241] By using preferred borate esterification reaction conditions, 15 g of a white solid compound (63% yield) was obtained from ethyl sulfonate compound formula 14 g. f =0.20 (PE / EA = 30 / 1). 1 H NMR(400MHz, CDCl3) δ8.40(d,J=1.3Hz,1H),7.92(dd,J=7.5,1.3Hz,1H),7.36(d,J =7.6Hz,1H),4.09(q,J=7.1Hz,2H),2.67(s,3H),1.35(s,12H),1.33–1.24(m,3H). 13C NMR(101MHz, CDCl3)δ141.2,139.8,136.0,134.2,132.0,126.1,84.3,66.7,24.8,20.5,14.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 15 H 24 BO5S + 327.1433, measured value 327.1430.

[0242] Synthesis of compound of formula 15h

[0243]

[0244] By using preferred borate esterification reaction conditions, a white solid compound was obtained from ethyl sulfonate compound formula 14h for 15h (75% yield). f =0.50 (PE / EA = 10 / 1). 1 H NMR (400MHz, CDCl3) δ8.35 (s, 1H), 8.06 (d, J = 7.4Hz, 1H), 7.98 (d, J = 8.0Hz, 1H), 7 .56(t,J=7.6Hz,1H),4.13(q,J=7.1Hz,2H),1.36(s,12H),1.30(d,J=7.1Hz,3H). 13 C NMR(101MHz, CDCl3)δ139.8,135.8,133.8,130.2,128.6,84.5,67.0,24.9,24.8,14.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 14 H 22 BO5S + 313.1276, measured value 313.1268.

[0245] Synthesis of compound 15i

[0246]

[0247] By using preferred borate esterification reaction conditions, compound 15i (90% yield) was obtained from ethyl sulfonate compound 14i as a white solid. f =0.20 (PE / EA = 10 / 1). 1H NMR (500MHz, CDCl3) δ9.08(s,1H),8.28(dd,J=7.4,1.2Hz,1H),8.10(d,J=8.2Hz,1H),7.98(d,J=8.1Hz,1H ),7.92(d,J=8.2Hz,1H),7.57(t,J=7.8Hz,1H),4.14(q,J=7.1Hz,2H),1.38(s,12H),1.28(t,J=7.1Hz,3H). 13 CNMR(126MHz, CDCl3)δ135.6,135.0,132.4,132.2,131.9,130.2,127.8,127.8,124.9,84.2,67.1,25.0,24.9,14.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 18 H 24 BO5S + 363.1433, measured value 363.1430.

[0248] Example 2

[0249] This embodiment describes the preparation method of compound (R)-1, which consists of 8 steps. The synthetic route is as follows:

[0250]

[0251] Includes the following steps:

[0252] (2.1) Step 1:

[0253] Preferably, the halogenation reaction conditions are as follows: Under nitrogen protection, the starting material (R)-3 (1.0 equivalent) is dissolved in tetrahydrofuran (0.1 mol / L) in a round-bottom flask of suitable capacity, and then the temperature is lowered to -78°C. Thiol(3.5 equivalent) is slowly added dropwise to the above reaction solution. After the addition is complete, the mixture is stirred at -78°C for 30 minutes, then heated to room temperature and stirred for another 3 hours until a light brown turbidity is formed. The temperature is then lowered to -78°C again, and iodine (3.75 equivalent) is added. After the addition is complete, the temperature is slowly raised to room temperature and stirred for 12 hours at room temperature. After the reaction is complete, the reaction is quenched with a saturated sodium sulfite aqueous solution, and extracted with diethyl ether. The extracted diethyl ether solution is washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the halogenated product (R)-4.

[0254] Synthesis of compound (R)-4b

[0255]

[0256] By using preferred halogenation reaction conditions, a yellowish-brown oily compound (R)-4b (27% yield) was obtained from the starting material (R)-3b. f =0.62 (PE / EA = 30 / 1). 1 H NMR (500MHz, CDCl3) δ8.47(s,2H),7.54(s,2H),7.16(d,J=8.7,1.6Hz,2H),7.12(d,J=8.7,2.0Hz,2H),4.81(d,J=5.7Hz,2 H), 4.70 (d, J = 5.7Hz, 2H), 2.73 (t, J = 7.7Hz, 4H), 2.62 (s, 6H), 1.68 (m, J = 7.3Hz, 4H), 1.28 (m, 52H), 0.90 (t, J = 6.7Hz, 6H). 13 C NMR (126MHz, CDCl3) δ151.5,151.5,140.6,139.5,132.6,132.4,128.8,126.5,126.3,125.1,99.5,92. 4,56.6,35.9,32.1,31.2,29.8,29.8,29.8,29.7,29.6,29.5,29.5,22.8,14.3.HRMS(APCI+)m / z:[M+H] + Calculated value C 56 H 85 I₂O₄ + 1075.4537, measured value 1075.4547.

[0257] Synthesis of compound (R)-4c

[0258]

[0259] By using preferred halogenation reaction conditions, a white solid compound of formula (R)-4c (70% yield) was obtained from the starting material compound of formula (R)-3c. f =0.55 (PE / EA = 30 / 1). 1 H NMR (400MHz, CDCl3) δ8.49(s,2H),7.62(d,J=2.0Hz,2H),7.37(dd,J=9.0,2.0Hz,2H),7.12(d,J=8.9Hz,2H),4.7 7(d,J=5.5Hz,2H),4.67(d,J=5.5Hz,2H),2.63(s,6H),2.15–2.09(m,6H),1.95(d,J=2.9Hz,12H),1.78(m,12H).13 C NMR(101MHz, CDCl3)δ151.5,149.0,140.1,132.6,132.2,126.3,126.1,125.6,121.8,99.4,92.1,56.8,43.1,36.9,36.4,29.0.HRMS(APCI+)m / z:[M+H] + Calculated value C 44 H 49 I₂O₄ + 895.1715, measured value 895.1719.

[0260] Synthesis of compound (R)-4d

[0261]

[0262] The synthesis of formula (R)-4d differs from the halogenation conditions described above. Due to the different types of starting materials, the preferred synthesis steps for formula (R)-4d are as follows: Under nitrogen protection, sodium hydride (60%, dispersed in mineral oil, 2.10 g, 52.5 mmol) is dissolved in 40 mL of tetrahydrofuran in a 100 mL round-bottom flask, and then the temperature is lowered to 0 °C. Formula (R)-3d (8.50 g, 15.0 mmol) is slowly added to the above reaction solution, and the mixture is stirred at 0 °C for 1.5 hours after the addition is complete. Subsequently, bromomethyl methyl ether (5.62 g, 45.0 mmol) is slowly added, and the mixture is stirred at 0 °C for 30 minutes. Thin-layer chromatography (TLC) analysis revealed that once the reaction was complete, it was quenched at 0°C with a saturated ammonium chloride aqueous solution. The mixture was extracted three times with ethyl acetate, and the resulting ethyl acetate solution was washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 20:1) to give a pale yellow solid compound (R)-4d (8.40 g, 87% yield). [α] D 19.2 = +10.8 (c = 0.26, CHCl3, (R)). 1 H NMR (400MHz, CDCl3) δ8.22(s,2H),7.70(s,2H),7.39(d,J=8.9Hz,2H),7.13(d,J=8.8Hz,2H),4.80(s,4H),2.61(s,6H),1.37(s,18H). 13C NMR (101MHz, CDCl3) δ149.6,149.0,133.0,131.7,131.4,127.2,126.4,126.0,122 .0,117.2,99.2,56.5,34.9,31.3.IR(neat)2956,1468,1352,1156,963,826,633cm - 1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 32 H 37 Br2O4 + 645.1033, measured value 645.1043.

[0263] Synthesis of compound (R)-4a'

[0264]

[0265] Compound (R)-4a' was obtained from the starting material compound (R)-3a' using preferred halogenation reaction conditions (R)-3a'). 1 H NMR (400MHz, CDCl3) δ8.44(s,1H),7.88(d,J=9.1Hz,1H),7.62(s,1H),7.57–7.50(m,2H),7.17–7.05(m,4H),5.11(d,J=6.9Hz,1H),5.03(d,J=6.9H z,1H),4.73(d,J=5.2Hz,1H),4.68(d,J=5.3Hz,1H),3.19(s,3H),2.74–7 .68(m,7H),1.73–1.59(m,4H),1.37–1.25(m,20H),0.88(t,J=6.5Hz,6H). 13 C NMR (101MHz, CDCl3) δ152.42,150.95,140.42,138.89,138.83,132.80,132.42,132.38, 129.90,129.57,128.58,128.49,126.53,126.26,126.18,125.52,125.23,120.43,116. 48,99.26,95.12,92.87,56.93,56.08,35.98,35.94,32.02,32.01,31.36,31.30,29.62 ,29.60,29.55,29.45,29.40,29.39,22.85,22.80,14.25,14.24.HRMS(APCI+)m / z:[M+H]+ Calculated value C 40 H 54 IO4 + 725.3062, measured value 725.3069.

[0266] (2.2) Step 2:

[0267] Preferably, the coupling reaction conditions are as follows: under nitrogen protection, the halogenated product (R)-4 obtained in step 1 (1.0 equivalent), the borate ester compound (15a-f) containing the SO2NMe2 group obtained in step 2 of Example 1 (3.0 equivalent), tetra-triphenylphosphine palladium (0.1 equivalent), potassium carbonate (3.0 equivalent), 1,2-dimethoxyethane, and water (volume ratio 6:1, so that the halogenated compound is 0.1 mol / L) are added sequentially to a three-necked flask equipped with a reflux condenser. The resulting mixture is stirred at 85°C for 16 hours. After the reaction is complete, the mixture is cooled to room temperature, quenched with saturated ammonium chloride aqueous solution, extracted three times with ethyl acetate, washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluent: petroleum ether and ethyl acetate) to obtain the coupling product (R)-5.

[0268] Synthesis of compound (R)-5a

[0269]

[0270] By using preferred coupling reaction conditions, a yellowish-brown solid compound of formula (R)-5a (86% yield) was obtained from the halogenated product of formula (R)-4a and the arylboronic ester compound of formula 15a. f =0.15 (PE / EA = 5 / 1).[α] D 18.8 = -36.0 (c = 0.25, CHCl3, (R)). 1 H NMR (500MHz, CDCl3) δ8.23 (s, 2H), 7.89 (d, J = 8.6Hz, 4H), 7.67 (s, 2H), 7.42 (d, J=7.9Hz,2H),7.21(d,J=8.7Hz,2H),7.16(dd,J=8.7,1.7Hz,2H),4.38(d,J=5.6 Hz,2H),4.30(d,J=5.6Hz,2H),2.88(s,12H),2.73(t,J=7.7Hz,4H),2.69(s,6H) ,2.39(s,6H),1.69(m,J=7.4Hz,4H),1.35–1.24(m,20H),0.87(t,J=6.6Hz,6H). 13C NMR (126MHz, CDCl3) δ150.3,140.3,137.4,137.0,136.4,133.9,133.6,132.9,132.3,131.2,130.7,130.2,128.6,126.6,126.5,126. 4,98.7,56.2,37.3,36.0,32.0,31.3,29.6,29.5,29.4,25.0,22.8,20.6,14.2.IR(neat)2922,1459,1325,1156,969,733,588,508cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 58 H 77 N2O8S2 + 993.5116, measured value 993.5114.

[0271] Synthesis of compound (R)-5b

[0272]

[0273] By using preferred coupling reaction conditions, a yellow oily compound, formula (R)-5b (48% yield), was obtained from the halogenated product of formula (R)-4b and the arylboronic ester compound of formula 15a. f =0.52 (PE / EA = 3 / 1). 1 H NMR(400MHz, CDCl3)δ8.23(d,J=1.9Hz,2H),7.92–7.86(m,4H),7.66(s,2H),7.4 2(d,J=8.0Hz,2H),7.21(d,J=8.7Hz,2H),7.16(dd,J=8.7,1.7Hz,2H),4.38(d,J =5.6Hz,2H),4.30(d,J=5.5Hz,2H),2.88(s,12H),2.72(t,J=7.8Hz,4H),2.69(s ,6H),2.39(s,6H),1.72–1.63(m,4H),1.32–1.21(m,52H),0.87(t,J=6.6Hz,6H). 13C NMR (101MHz, CDCl3) δ150.3,140.3,137.4,137.0,136.4,133.9,133.6,132.9,132.3,131.2,130.7,130.2,128.6,126.6,126.5 ,126.4,98.7,56.2,37.3,36.0,32.1,31.3,29.8,29.8,29.8,29.7,29.6,29.5,25.0,22.8,20.6,14.3.HRMS(APCI+)m / z:[M+H] + Calculated value C 74 H 109 N2O8S2 + 1217.7625, measured value 1217.7614.

[0274] Synthesis of compound (R)-5c

[0275]

[0276] By using preferred coupling reaction conditions, a yellow solid compound of formula (R)-5c (85% yield) was obtained from the halogenated product of formula (R)-4c and the arylboronic ester compound of formula 15a. f =0.22 (PE / EA = 5 / 1). 1 HNMR(400MHz, CDCl3)δ8.22(d,J=1.9Hz,2H),7.92(s,2H),7.88(dd,J=7.9, 2.0Hz,2H),7.77(d,J=2.0Hz,2H),7.43–7.15(m,4H),7.25–7.21(d,J=8.9H z,2H),4.38(d,J=5.5Hz,2H),4.31(d,J=5.6Hz,2H),2.88(s,12H),2.69(s, 6H), 2.39 (s, 6H), 2.12 (s, 6H), 1.99 (d, J = 2.9Hz, 12H), 1.85–1.73 (m, 12H). 13 C NMR (101MHz, CDCl3) δ150.4,148.6,137.5,136.9,136.3,136.0,133.9,133.4,132.9,132.2,131.0,13 0.7,126.4,125.2,123.1,98.7,83.6,56.2,43.2,37.3,37.0,36.5,29.1,20.6.HRMS(ESI+)m / z:[M+H] + Calculated value C 62 H 73N2O8S2 + 1037.4803, measured value 1037.4813.

[0277] Synthesis of compound (R)-5d

[0278]

[0279] Since the preferred coupling reaction conditions could not successfully synthesize compound (R)-5d, more preferred reaction conditions for compound (R)-5d are provided here, with the following specific steps: Under nitrogen protection, compound (R)-4d (5.00 g, 8.0 mmol), compound 15b (7.70 g, 24.0 mmol), tetraphenylphosphine palladium (0.92 g, 0.8 mmol), barium hydroxide octahydrate (7.57 g, 24.0 mmol), 60 mL of 1,4-dioxane, and 20 mL of water were added sequentially to a three-necked flask equipped with a reflux condenser. The resulting mixture was stirred at 85 °C for 16 hours. After the reaction was complete, the mixture was cooled to room temperature and quenched with a saturated ammonium chloride aqueous solution. The mixture was extracted three times with ethyl acetate. The extracted ethyl acetate solution was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3:1) to give a pale yellow solid compound (R)-5d (3.35 g, 74% yield). f =0.16 (PE / EA = 3 / 1).[α] D 19.3 = -30.6 (c = 0.26, CHCl3, (R)). 1 H NMR (400MHz, CDCl3) δ8.15(s,2H),8.03(d,J=7.8Hz,2H),7.95(s,2H),7.86–7.73(m,4H),7.65(t,J=7.8Hz,2H),7.42(d,J =9.2Hz,2H),7.23(d,J=9.2Hz,2H),4.38(d,J=5.6Hz,2H),4.32(d,J=5.8Hz,2H),2.78(s,12H),2.41(s,6H),1.40(s,18H). 13C NMR (101MHz, CDCl3) δ150.5,148.5,140.5,135.9,134.3,133.7,132.2,131.0,130.9,129.0,128.7,126.5 ,126.3,126.2,123.2,98.8,56.2,38.2,34.9,31.3,25.0.IR(neat)2956,1461,1345,1163,970,710,584cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 48 H 57 N2O8S2 + 853.3551, measured value 853.3553.

[0280] Synthesis of compounds of formula (R)-5e

[0281]

[0282] Since the preferred coupling reaction conditions could not successfully synthesize compound (R)-5e, more preferred reaction conditions for compound (R)-5e are provided here, with the following specific steps: Under nitrogen protection, compound (R)-4e (508.0 mg, 0.9 mmol), compound 14c (749.7 mg, 2.2 mmol), tetrakis(triphenylphosphine)palladium (104.0 mg, 0.09 mmol), potassium carbonate (309.6 mg, 2.2 mmol), 6 mL of 1,2-dimethoxyethane, and 1 mL of water were added sequentially to a three-necked flask equipped with a reflux condenser. The resulting mixture was stirred at 85 °C for 16 hours. After the reaction was complete, the mixture was cooled to room temperature and quenched with a saturated ammonium chloride aqueous solution. The mixture was extracted three times with ethyl acetate, and the resulting ethyl acetate solution was washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to give a white solid compound (R)-5e (757.6 mg, 99% yield). f =0.48 (PE / EA = 5 / 1). 1H NMR(500MHz, CDCl3)δ8.25(d,J=1.9Hz,2H),7.99(s,2H),7.97–7.87(m,4H),7.49–7.40(m,4H),7.30(ddd,J=8.1,6.7,1.3Hz,2H),7. 22(dd,J=8.5,1.1Hz,2H),3.17(s,6H),3.07–3.01(m,4H),2.85(s,12H),1.75–1.68(m,4H),1.47–1.35(m,8H),0.93(t,J=6.9Hz,6H). 13 C NMR (126MHz, CDCl3) δ153.9,142.3,136.7,135.9,134.0,133.6,133.3,131.9,130.9,130.8,130.5,12 8.3,126.9,126.0,125.9,125.5,60.8,37.3,33.1,32.2,31.5,27.1,22.7,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 48 H 57 N2O6S2 + 821.3653, measured value 821.3641.

[0283] Synthesis of compound (R)-5f

[0284]

[0285] By using preferred coupling reaction conditions, a pale yellow solid compound of formula (R)-5f (73% yield) was obtained from the halogenated product of formula (R)-4a and the arylboronic ester compound of formula 15d. f =0.14 (PE / EA = 5 / 1). 1H NMR (500MHz, CDCl3) δ9.09(s,2H),8.27(d,J=7.5Hz,2H),8.12(d,J=8.2Hz,2H),8.03(d,J= 2.4Hz,4H),8.00(s,2H),7.70(d,J=1.7Hz,2H),7.58(t,J=7.8Hz,2H),7.33(d,J=8.6Hz,2H ),7.21(d,J=8.7Hz,2H),4.39(d,J=5.6Hz,2H),4.35(d,J=5.6Hz,2H),2.89(s,12H),2.76( t,J=7.8Hz,4H),2.31(s,6H),1.74–1.66(m,4H),1.36–1.25(m,20H),0.87(t,J=6.6Hz,6H). 13 C NMR (126MHz, CDCl3) δ150.5,140.2,139.2,135.0,134.2,133.6,133.1,132.4,131.3,130.9,130.7,129.3,129.1,128.7,128. 5,126.8,126.6,126.5,125.8,124.3,98.8,56.0,37.5,36.1,32.0,31.4,29.6,29.5,29.4,22.8,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 64 H 77 N2O8S2 + 1065.5116, measured value 1065.5109.

[0286] Synthesis of compound (R)-5g

[0287]

[0288] By using preferred coupling reaction conditions, a yellow oily compound, formula (R)-5g (91% yield), was obtained from the halogenated product (R)-4a and the arylboronic ester compound (R)-15e. f =0.14 (PE / EA = 5 / 1). 1H NMR(400MHz, CDCl3)δ8.26(d,J=1.9Hz,2H),7.90–7.80(m,4H),7.66(d,J=1.6Hz,2H),7.39 (d,J=7.9Hz,2H),7.21(d,J=8.7Hz,2H),7.15(dd,J=8.7,1.7Hz,2H),4.36(d,J=5.6Hz,2H), 4.30(d,J=5.6Hz,2H),3.39(q,J=7.1Hz,8H),2.73(t,J=7.7Hz,4H),2.67(s,6H),2.36(s,6H ),1.68(p,J=7.2Hz,4H),1.39–1.24(m,20H),1.18(t,J=7.1Hz,12H),0.86(t,J=6.9Hz,6H). 13 CNMR(101MHz, CDCl3)δ150.4,140.2,138.9,137.2,136.6,133.7,133.5,132.8,132.3,131.2,130.2,130.1,128.5,12 6.7,126.5,126.4,98.6,56.1,41.2,36.0,32.0,31.3,29.6,29.5,29.4,22.8,20.2,14.2,14.0.HRMS(ESI+)m / z:[M+H] + Calculated value C 62 H 85 N2O8S2 + 1049.5747, measured value 1049.5727.

[0289] Synthesis of compound (R)-5h

[0290]

[0291] Since the preferred coupling reaction conditions could not successfully synthesize compound (R)-5h, more preferred reaction conditions for compound (R)-5h are provided here, with the following steps: using the same reaction conditions as for the synthesis of compound (R)-5d, compound (R)-4a and compound (R)-15f were reacted to give the yellow solid compound (R)-5h (66% yield). f =0.31 (PE / EA = 2 / 1). 1H NMR (500MHz, CDCl3) δ8.35(s,4H),8.17(s,2H),7.93(s,2H),7.72(s,2H),7.22(q,J=8.7Hz,4H),4.38(d,J=5.5Hz,2H),4.29(d,J =5.5Hz,2H),2.83(s,24H),2.78–2.74(m,4H),2.50(s,6H),1.70(t,J=7.2Hz,4H),1.31(d,J=43.3Hz,20H),0.87(t,J=6.6Hz,6H). 13 C NMR (126MHz, CDCl3) δ149.8,141.7,140.9,137.7,132.6,132.2,132.1,130.9,130.5,129.4,126.7,126.4, 126.1,125.1,98.9,56.3,38.0,35.9,31.9,31.1,29.5,29.4,29.3,24.9,22.7,14.1.HRMS(ESI+)m / z:[M+H] + Calculated value C 60 H 83 N4O 12 S4 + 1179.4885, measured value 1179.4869.

[0292] Synthesis of compound (R)-5i

[0293]

[0294] By using preferred coupling reaction conditions, a pale yellow oily compound, formula (R)-5i (85% yield), was obtained from the halogenated product (R)-4a' and the arylboronic ester compound (R)-15a. HRMS(ESI+) m / z: [M+H] + Calculated value C 49 H 66 NO6S + 708.4082, measured value 796.4600.

[0295] Synthesis of compound (R)-5j

[0296]

[0297] By using preferred coupling reaction conditions, a white solid compound of formula (R)-5j (97% yield) was obtained from the halogenated product of formula (R)-4f and the arylboronic ester compound of formula 15b. f =0.17 (PE / EA = 4 / 1). 1H NMR (500MHz, CDCl3) δ8.17(s,2H),8.05(d,J=7.8Hz,2H),8.00(s,2H),7.94(d,J=8.0Hz,2H),7.82(d,J=7.6Hz,2H),7.67(t,J= 7.8Hz,2H),7.47(t,J=7.4Hz,2H),7.36–7.28(m,4H),4.39(d,J=5.6Hz,2H),4.32(d,J=5.7Hz,2H),2.79(s,12H),2.40(s,6H). 13 C NMR (126MHz, CDCl3) δ151.0,140.2,136.0,134.2,134.0,133.8,131.0,130.9,129.1,12 8.6,128.2,127.1,126.6,126.6,126.4,125.8,98.8,56.1,38.1.HRMS(ESI+)m / z:[M+H] + Calculated value C 40 H 41 N2O8S2 + 741.2299, measured value 741.2290.

[0298] Synthesis of compound (R)-5k

[0299]

[0300] By using preferred coupling reaction conditions, a yellow solid compound of formula (R)-5k (99% yield) was obtained from the halogenated product of formula (R)-4f and the arylboronic ester compound of formula 15d. f =0.28 (PE / EA = 3 / 1). 1 H NMR (500MHz, CDCl3) δ9.10 (s, 2H), 8.27 (d, J = 7.3Hz, 2H), 8.13 (d, J = 8.1Hz, 2H), 8.06 (d, J = 20.4Hz, 6H), 7.95 (d, J = 8.2Hz, 2H), 7.59 (t, J = 7.8Hz, 2H),7.47(t,J=7.1Hz,3H),7.41(d,J=8.3Hz,2H),7.37(d,J=6.5Hz,2H), 4.40(d,J=5.6Hz,2H),4.36(d,J=5.7Hz,2H),2.89(s,12H),2.31(s,6H). 13C NMR (126MHz, CDCl3) δ151.2,138.8,135.0,134.1,133.8,133.5,133.0,131.2,130.9,130.8,129.2,128. 8,128.6,128.1,126.8,126.7,126.5,125.7,125.5,124.3,98.7,55.9,37.3,24.9.HRMS(ESI+)m / z:[M+H] + Calculated value C 48 H 45 N2O8S2 + 841.2612, measured value 841.2607.

[0301] Synthesis of compound (R)-5l

[0302]

[0303] Since the preferred coupling reaction conditions could not be successfully used to synthesize compound (R)-5l, more preferred reaction conditions for compound (R)-5l are provided here, and the specific steps are as follows: using the same reaction conditions as for the synthesis of compound (R)-5d, compound (R)-4f and compound (R)-15j were reacted to give compound (R)-5l (78% yield) as a yellow solid. f =0.30 (PE / EA = 30 / 1). 1 H NMR (400MHz, CDCl3) δ8.02(s,1H),7.97(d,J=6.7Hz,2H),7.92(d,J=8.2Hz,1H),7.65(d,J=7.8Hz,1H),7.60(t, J=7.7Hz,1H),7.50–7.41(m,1H),7.36–7.25(m,2H),4.40(d,J=5.9Hz,1H),4.35(d,J=5.9Hz,1H),2.40(s,3H). 13 C NMR (101MHz, CDCl3) δ151.4,140.0,134.3,134.0,133.4,131.0,130.9,12 8.9,128.2,127.0,126.6,126.5,126.4,125.7,124.2,124.2,98.9,56.1. 19 F NMR(376MHz, CDCl3)δ-62.4.IR(neat)2970,1339,1128,970,805,704cm -1 .HRMS(ESI+)m / z:[M+H] +Calculated value C 38 H 29 F6O4 + 663.1965, measured value 663.1969.

[0304] (2.3) Step 3:

[0305] Preferably, the deprotection reaction conditions are as follows: The coupling product (R)-5 (1.0 equivalent) obtained in step 2 and 1,4-dioxane (0.1 mol / L) obtained in step 2 are added sequentially to a round-bottom flask equipped with a reflux condenser. Concentrated hydrochloric acid (10.0 equivalent) is then added, and the resulting mixture is stirred at 60°C for 5 hours. After the reaction is complete, the mixture is cooled to room temperature, quenched with a saturated sodium bicarbonate aqueous solution, and extracted three times with ethyl acetate. The extracted ethyl acetate solution is washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the desired deprotected product (R)-6.

[0306] Synthesis of compound (R)-6a

[0307]

[0308] By using preferred deprotection reaction conditions, a pale yellow solid compound (R)-6a (98% yield) was obtained from the coupling product (R)-5a. f =0.15 (PE / EA = 5 / 1).[α] D 18.9 = +55.2 (c = 0.26, CHCl3, (R)). 1 H NMR (400MHz, CDCl3) δ8.29(d,J=1.9Hz,2H),7.99(s,2H),7.85(dd,J=7.9,2.0Hz,2H),7.71(s,2H),7.42(d,J=7.9Hz,2H),7.20(dd,J=8.6,1.7Hz,2H), 7.13(d,J=8.6Hz,2H),5.25(s,2H),2.83(s,12H),2.74(t,J=7.7Hz,4H),2. 69(s,6H),1.67(t,J=6.9Hz,4H),1.30–1.23(m,20H),0.87(t,J=6.0Hz,6H). 13C NMR (101MHz, CDCl3) δ149.5,139.4,137.1,135.8,135.7,133.7,132.8,131.3,131.2,131.2,129.6,129.6,128.6,127.0,124.0 ,111.8,37.2,35.8,31.9,31.4,29.5,29.3,29.3,22.7,20.6,14.1.IR(neat)3430,2930,1452,1322,1132,952,726,585,497cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 58 H 77 N2O8S2 + 905.4592, measured value 905.4571.

[0309] Synthesis of compound (R)-6b

[0310]

[0311] By using preferred deprotection reaction conditions, the yellow liquid compound (R)-6b (92% yield) was obtained from the coupling product (R)-5b. f =0.52 (PE / EA = 3 / 1). 1 H NMR(500MHz, CDCl3)δ8.31(d,J=1.9Hz,2H),8.00(s,2H),7.86(dd,J=7.9,2.0H z,2H),7.72(d,J=1.7Hz,2H),7.42(d,J=8.0Hz,2H),7.21(dd,J=8.7,1.8Hz,2H ),7.15(d,J=8.6Hz,2H),5.32(s,2H),2.83(s,12H),2.75(t,J=8.9,6.5Hz,4H) ,2.69(s,6H),1.69(m,J=7.6Hz,4H),1.46–1.19(m,52H),0.89(t,J=6.8Hz,6H). 13C NMR (126MHz, CDCl3) δ149.6,139.4,137.1,135.9,135.7,133.7,132.8,131.4,131.3,131.2,129.7,129.6,128.7,127 .1,124.1,112.0,37.3,35.9,32.0,31.5,29.8,29.8,29.7,29.7,29.6,29.4,22.8,20.6,14.2.HRMS(APCI+)m / z:[M+H] + Calculated value C 70 H 101 N2O8S2 + 1129.7096, measured value 1129.7083.

[0312] Synthesis of compound (R)-6c

[0313]

[0314] By using preferred deprotection reaction conditions, a pale yellow solid compound of formula (R)-6c (88% yield) was obtained from the coupling product of formula (R)-5c. f =0.22 (PE / EA = 5 / 1). 1 H NMR(400MHz, CDCl3)δ8.30(d,J=1.9Hz,2H),8.04(s,2H),7.88–7.82(m,4H),7.47–7.38(m,4H),7.18(d,J =8.8Hz,2H),5.30(s,2H),2.83(s,12H),2.69(s,6H),2.13(s,6H),1.98(d,J=2.9Hz,12H),1.79(m,12H). 13 C NMR (101MHz, CDCl3) δ149.8,147.8,137.2,136.0,133.8,132.9,131.9,131.3,129.6,128.6,126 .4,124.0,120.0,116.9,111.8,83.6,72.9,43.2,37.4,36.9,29.0,20.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 58 H 65 N2O8S2 + 949.4279, measured value 949.4269.

[0315] Synthesis of compound (R)-6d

[0316]

[0317] By using preferred deprotection reaction conditions, a yellow solid compound of formula (R)-6d (88% yield) was obtained from the coupling product formula (R)-5d. f =0.16 (PE / EA = 3 / 1). 1 H NMR(500MHz, CDCl3)δ8.21(d,J=1.9Hz,2H),8.09(s,2H),8.03–7.98(m,2H),7.91(s,2H),7.79(d,J=7.7Hz,2H),7 .65(t,J=7.8Hz,2H),7.48(dt,J=8.8,1.5Hz,2H),7.20(d,J=8.9Hz,2H),5.32(s,2H),2.74(s,12H),1.41(s,18H). 13 C NMR (101MHz, CDCl3) δ149.7,147.8,138.9,135.4,133.9,132.2,131.3,129.5,129.1,129.0,128.7,127.3 ,126.7,124.0,123.9,111.8,38.2,34.8,31.3.IR(neat)3511,2960,1447,1339,1163,956,710,584,497cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 44 H 49 N2O6S2 + 765.3027, measured value 765.3022.

[0318] Synthesis of compounds of formula (R)-6e

[0319]

[0320] Since the preferred deprotection reaction conditions could not successfully synthesize compound (R)-6e, more preferred reaction conditions for compound (R)-6e are provided here, with the following steps: Compound (R)-5e (821.1 mg, 1.0 mmol) and 20 mL of dichloromethane were added sequentially to a 100 mL round-bottom flask, followed by cooling to -78 °C, and boron tribromide (2.50 g, 10.0 mmol) was slowly added dropwise. The resulting mixture was slowly heated to room temperature and stirred for 30 minutes. After the reaction was complete, the mixture was quenched with ice water, extracted three times with dichloromethane, and the extracted dichloromethane solution was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to give a pale yellow solid compound (R)-6e (814.3 mg, 99% yield). f =0.48 (PE / EA = 5 / 1). 1 HNMR(500MHz, CDCl3)δ8.29(d,J=2.0Hz,2H),8.06(s,2H),7.97–7.91(m,2H),7.88(dd,J=8 .0,1.9Hz,2H),7.47(d,J=8.0Hz,2H),7.41(ddd,J=8.1,6.9,1.2Hz,2H),7.34(ddd,J=8.4, 6.0,4.6Hz,2H),7.22–7.18(m,2H),5.45(s,2H),3.06–2.99(m,4H),2.81(s,12H),1.70(dd d,J=15.5,9.4,6.2Hz,4H),1.48–1.31(m,8H),0.92(t,J=7.0Hz,6H).HRMS(ESI+)m / z:[M+H] + Calculated value C 46 H 53 N2O6S2 + 793.3340, measured value 793.3251.

[0321] Synthesis of compound (R)-6f

[0322]

[0323] By using preferred deprotection reaction conditions, a yellow solid compound of formula (R)-6f (57% yield) was obtained from the coupling product formula (R)-5f. f =0.48 (PE / EA = 5 / 1). 1H NMR (400MHz, CDCl3) δ9.13(s,2H),8.23(dd,J=7.4,1.3Hz,2H),8.11(d,J=8.4Hz,4H),8.01(s,4H),7.75(s,2H),7.57(t,J=7.8Hz, 2H),7.24(s,4H),5.41(s,2H),2.84(s,12H),2.75(t,J=7.7Hz,4H),1.75–1.65(m,4H),1.39–1.25(m,21H),0.87(d,J=7.4Hz,6H). 13 C NMR (126MHz, CDCl3) δ149.9,139.4,137.8,134.1,133.7,133.1,131.9,131.5,130.8,130.3,129.9,129.6,129.3,129.0,1 28.6,127.3,126.0,124.4,124.3,112.3,37.6,36.0,32.0,31.5,29.6,29.6,29.5,29.4,22.8,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 60 H 69 N2O6S2 + 977.4592, measured value 977.4592.

[0324] Synthesis of compound (R)-6g

[0325]

[0326] By using preferred deprotection reaction conditions, a yellow liquid compound, formula (R)-6 g (96% yield), was obtained from the coupling product formula (R)-5 g. f =0.14 (PE / EA = 5 / 1). 1 H NMR (500MHz, CDCl3) δ8.31 (s, 2H), 7.98 (s, 2H), 7.83 (d, J = 7.9Hz, 2H), 7.71 ( s,2H),7.39(d,J=7.9Hz,2H),7.21(s,2H),7.14(d,J=8.6Hz,2H),5.25(s,2H) ,3.35(q,J=7.2Hz,8H),2.74(t,J=7.7Hz,4H),2.66(s,6H),1.68(p,J=7.7,7 .2Hz,4H),1.39–1.23(m,20H),1.15(t,J=7.2Hz,12H),0.87(t,J=6.6Hz,6H). 13C NMR (126MHz, CDCl3) δ149.6,139.5,138.5,136.8,135.8,133.5,132.7,131.4,131.3,130.7,129.8,129.6,128. 9,127.2,124.2,112.0,41.0,36.0,32.0,31.5,29.6,29.5,29.4,22.8,20.2,14.2,13.9.HRMS(ESI+)m / z:[M+H] + Calculated value C 58 H 77 N2O6S2 + 961.5206, measured value 961.5223.

[0327] Synthesis of compound (R)-6h

[0328]

[0329] By using preferred deprotection reaction conditions, the coupling product formula (R)-5h was given as a yellow solid compound formula (R)-6h (89% yield). f =0.31 (PE / EA = 2 / 1). 1 H NMR (400MHz, CDCl3) δ8.43–8.38(m,4H),8.11(d,J=34.0Hz,4H),7.77(s,2H),7.31–7.26(m,2H),7.13(d,J=8.6Hz,2H ),5.47(s,2H),2.81(s,24H),2.76(t,J=7.9Hz,4H),1.69(p,J=7.3Hz,4H),1.39–1.19(m,20H),0.87(t,J=6.5Hz,6H). 13 C NMR (101MHz, CDCl3) δ149.2,140.4,140.3,137.4,136.6,132.5,131.9,130.6,129.7,127.4,127.0 ,125.3,124.1,112.1,43.0,38.1,32.0,31.4,29.6,29.4,29.4,22.8,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 56 H 75 N4O 10 S4 + 1091.4361, measured value 1091.4335.

[0330] Synthesis of compound (R)-6i

[0331]

[0332] By using preferred deprotection reaction conditions, the yellow liquid compound (R)-6i (95% yield) was obtained from the coupling product (R)-5i. 1 H NMR(400MHz, CDCl3)δ8.28(d,J=2.0Hz,1H),7.97(s,1H),7.91(d,J=8.9Hz,1H), 7.84(dd,J=7.8,2.0Hz,1H),7.68(dd,J=14.1,1.7Hz,2H),7.38(dd,J=21.1,8.4 Hz,2H),7.23–7.10(m,3H),7.07(d,J=8.6Hz,1H),5.22(s,1H),5.08(s,1H),2.8 2(s,6H),2.77–2.66(m,7H),1.66(m,4H),1.39–1.20(m,20H),0.91–0.83(m,6H). 13 C NMR (101MHz, CDCl3) δ152.3,149.5,139.4,138.9,137.1,136.1,135.8,133.8,1 32.8,131.8,131.5,131.2,131.2,131.1,129.8,129.7,129.5,129.3,128.6,12 8.2,127.1,127.0,125.0,124.2,117.8,112.3,110.8,38.1,37.4,35.9,35.9,3 2.0,31.5,31.5,29.6,29.5,29.5,29.4,22.8,20.7,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 45 H 58 NO4S + 708.4082, measured value 708.4085.

[0333] Synthesis of compound (R)-6j

[0334]

[0335] By using preferred deprotection reaction conditions, a white solid compound of formula (R)-6j (97% yield) was obtained from the coupling product of formula (R)-5j. f =0.25 (PE / EA = 3 / 1). 1H NMR (500MHz, CDCl3) δ8.23(s,2H),8.12(s,2H),8.05–7.96(m,4H),7.81(d,J=7.7Hz,2H),7.68(t,J=7.8 Hz,2H),7.47(t,J=7.5Hz,2H),7.40(t,J=7.5Hz,2H),7.24(d,J=8.3Hz,2H),5.45(s,2H),2.76(s,12H). 13 C NMR (126MHz, CDCl3) δ150.1,138.6,135.4,133.8,133.2,132.1,129.5,129.0, 128.8,128.7,128.2,126.7,124.9,124.1,111.9,38.1.HRMS(ESI+)m / z:[M+H] + Calculated value C 36 H 33 N2O6S2 + 653.1775, measured value 653.1759.

[0336] Synthesis of compound (R)-6k

[0337]

[0338] By using preferred deprotection reaction conditions, a white solid compound of formula (R)-6k (99% yield) was obtained from the coupling product formula (R)-5k. f =0.48 (PE / EA = 1 / 1). 1 H NMR (500MHz, CDCl3) δ9.14(s,2H),8.21(d,J=7.3Hz,2H),8.16(s,2H),8.09(d,J=8.2Hz,2H),8.00(s,4H),7.96(d,J=8.1Hz ,2H),7.55(t,J=7.8Hz,2H),7.42(t,J=7.4Hz,2H),7.36(t,J=7.6Hz,2H),7.30(d,J=8.4Hz,2H),5.52(s,2H),2.83(s,12H). 13 C NMR (126MHz, CDCl3) δ150.5,137.5,134.1,133.7,133.1,132.9,132.4,130.7,130.4,129.6,129 .2,128.9,128.8,128.7,127.9,125.9,124.7,124.4,124.2,112.2,37.5.HRMS(ESI+)m / z:[M+H]+ Calculated value C 44 H 37 N2O6S2 + 753.2088, measured value 753.2081.

[0339] Synthesis of compound (R)-6l

[0340]

[0341] By using preferred deprotection reaction conditions, a pale yellow solid compound of formula (R)-6l (95% yield) was obtained from the coupling product formula (R)-5l. f =0.30 (PE / EA = 30 / 1). 1 H NMR(400MHz, CDCl3)δ8.06(d,J=15.3Hz,4H),8.00–7.93(m,4H),7.67(d,J=7.9Hz, 2H),7.60(d,J=7.8Hz,2H),7.47–7.34(m,4H),7.23(d,J=8.3Hz,2H),5.36(s,2H). 13 C NMR (101MHz, CDCl3) δ150.2,138.4,133.2,133.1,132.1,129.6,129.4,128.9,128.8,128.2,126.7,124.9,124.5,124.2,121.4,112.1. 19 FNMR(376MHz, CDCl3)δ-62.5.IR(neat)3524,2963,1622,1331,1237,1117,868,753,700cm - 1 .HRMS(ESI+)m / z:[M+H] + Calculated value C 34 H 21 F6O2 + 575.1440, measured value 575.1440.

[0342] (2.4) Step 4:

[0343] Preferably, the acylation reaction conditions are as follows: Under nitrogen protection, the deprotected compound of formula (R)-6 (1.0 equivalent) obtained in step 3 and N,N-dimethylformamide (0.5 mol / L) are added sequentially to a round-bottom flask equipped with a reflux condenser. After cooling to 0°C, sodium hydride (5.0 equivalent) is added in portions. After stirring at room temperature for 10 minutes, dimethylaminothioformyl chloride (5.0 equivalent) is added. Subsequently, the resulting mixture is heated to 85°C and maintained at this temperature with stirring for 18 hours. After the reaction is complete, the mixture is cooled to room temperature and the reaction is quenched with 2% potassium hydroxide aqueous solution. A large amount of insoluble matter precipitates out, which is filtered through a sintered glass funnel and washed with 2% potassium hydroxide aqueous solution. The filtered insoluble matter is dissolved in dichloromethane, and the resulting solution is washed successively with water and saturated brine. After drying with anhydrous sodium sulfate, the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the acylated product of formula (R)-7.

[0344] Synthesis of compound (R)-7a

[0345]

[0346] By using preferred acylation reaction conditions, a yellow solid compound (R)-7a (86% yield) was obtained from the deprotected product (R)-6a. f =0.30 (PE / EA = 2 / 1).[α] D 18.9 = -53.7 (c = 0.26, CHCl3, (R)). 1 H NMR (500MHz, CDCl3) δ8.22–7.02(m,14H),3.20–0.82(m,64H). 13 C NMR (126MHz, CDCl3, only major of three rotational isomers for each signal reported)δ185.5,162.6,146.5,141.0,136.9,136.8,135.4,133.7,133.1,133.0,132.0,131.5,131.2,129.9,128.2,126.1,126.0,6 0.5,42.8,37.5,37.0,36.0,32.0,31.4,31.1,29.6,29.3,22.8,20.5,14.2.IR(neat)2922,1660,1526,1375,1316,1142,955,728,588 494cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C60 H 79 N4O6S4 + 1079.4877, measured value 1079.4868.

[0347] Synthesis of compound (R)-7b

[0348]

[0349] By using preferred acylation reaction conditions, a pale yellow solid compound of formula (R)-7b (73% yield) was obtained from the deprotected product formula (R)-6b. f =0.31 (PE / EA = 3 / 1). 1 H NMR (400MHz, CDCl3) δ8.23–7.01(m,14H),3.65–0.81(m,96H). 13 C NMR (101MHz, CDCl3, only major of three rotational isomers for each signal reported) δ194.9,185.5,163.1,146.5,141.0,136.9,136.9,135.4,133.8,133.1,132.0,131.5,131.2,129.9,128. 2,126.1,126.0,42.8,38.4,37.5,37.0,36.1,32.0,31.2,29.8,29.7,29.5,22.8,20.5,14.2.HRMS(APCI+)m / z:[M+H] + Calculated value C 76 H 111 N4O6S4 + 1303.7381, measured value 1303.7391.

[0350] Synthesis of compound (R)-7c

[0351]

[0352] By using preferred acylation reaction conditions, a pale yellow solid compound of formula (R)-7c (49% yield) was obtained from the deprotected product formula (R)-6c. f =0.45 (PE / EA = 2 / 1). 1 H NMR (400MHz, CDCl3) δ8.23–7.27(m,14H),3.23–1.72(m,60H). 13C NMR (101MHz, CDCl3, only major of three rotational isomers for each signal reported)δ185.6,149.1,146.6,137.0,136.8,135.3,133.8,133.0,133.0,131.9,131.2,130.5,1 30.0,128.1,125.7,124.8,122.9,43.2,42.8,37.5,37.1,36.9,29.0,20.5.HRMS(APCI+)m / z:[M+H] + Calculated value C 64 H 75 N4O6S4 + 1123.4564, measured value 1123.4559.

[0353] Synthesis of compound (R)-7d

[0354]

[0355] By using preferred acylation reaction conditions, a pale yellow solid compound of formula (R)-7d (45% yield) was obtained from the deprotected product formula (R)-6d. f =0.40 (PE / EA = 2 / 1).[α] D 19.3 = +7.8 (c = 0.26, CHCl3, (R)). 1 H NMR (400MHz, CDCl3) δ8.16–7.30(m,16H),3.19–1.34(m,42H). 13 C NMR (101MHz, CDCl3, only major of three rotational isomers for each signal reported)δ185.5,162.6,149.1,146.6,139.9,135.5,133.8,133.2,131.7,130.6,129.8,129.1,128.5,128 .1,126.3,125.6,123.0,42.2,38.1,34.9,31.3.IR(neat)2967,1675,1528,1345,1160,956,714,584,489cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 50 H 59 N4O6S4 +939.3312, measured value 939.3310.

[0356] Synthesis of compounds of formula (R)-7e

[0357]

[0358] By using preferred acylation reaction conditions, a yellow solid compound of formula (R)-7e was obtained from the deprotected product formula (R)-6e (83% yield). f =0.52 (PE / EA = 5 / 1). 1 H NMR(400MHz, CDCl3)δ8.23–7.20(m,16H),3.33–0.71(m,46H).HRMS(ESI+)m / z:[M+H] + Calculated value C 52 H 62 N4O6S4 + 967.3625, measured value 967.3602.

[0359] Synthesis of compound (R)-7f

[0360]

[0361] By using preferred acylation reaction conditions, a yellow solid compound of formula (R)-7f was obtained from the deprotected product formula (R)-6f (64% yield). f =0.60 (PE / EA = 1 / 1). 1 H NMR (500MHz, CDCl3) δ9.12–7.04(m,20H),3.18–0.80(m,58H). 13 C NMR (126MHz, CDCl3, only major of three rotational isomers for each signal reported)δ185.5,146.9,140.8,138.7,134.9,134.0,133.4,133.0,131.9,131.5,130.4,129.4,129.3,129.0,128.4,127.9,126 .0,125.9,125.9,124.1,42.6,38.6,37.9,37.7,37.3,36.0,31.9,31.1,29.5,29.5,29.3,29.3,22.7,14.1.HRMS(ESI+)m / z:[M+H] + Calculated value C 66 H 79 N4O6S4 +1151.4877, measured value 1151.4852.

[0362] Synthesis of compound (R)-7g

[0363]

[0364] By using preferred acylation reaction conditions, a white solid compound of formula (R)-7 g (50% yield) was obtained from the deprotected product formula (R)-6 g. f =0.64 (PE / EA = 2 / 1). 1 H NMR (400MHz, CDCl3) δ8.26–7.02(m,14H),3.52–0.71(m,72H). 13 C NMR (101MHz, CDCl3, only major of three rotational isomers for each signal reported)δ185.5,146.5,141.0,137.9,136.8,136.5,133.5,133.3,132.8,132.1,131.6,131.0,129.9,128.3,12 8.2,126.1,126.0,42.8,40.7,38.4,36.1,32.0,31.2,29.6,29.4,22.8,20.1,14.2,13.8.HRMS(APCI+)m / z:[M+H] + Calculated value C 64 H 75 N4O6S4 + 1135.5508, measured value 1135.5501.

[0365] Synthesis of compound (R)-7h

[0366]

[0367] By using preferred acylation reaction conditions, a yellow solid compound of formula (R)-7h (76% yield) was obtained from the deprotected product formula (R)-6h. f =0.48 (PE / EA = 1 / 1). 1 H NMR (500MHz, CDCl3) δ8.28–7.09(m,14H),3.68–0.69(m,70H). 13C NMR (126MHz, CDCl3, only major of three rotational isomers for each signal reported)δ184.7,154.5,141.8,137.5,137.2,137.0,132.7,132.5,132.2,131.9,131.5,130 .2,126.7,126.6,38.1,38.1,37.9,31.9,31.4,29.5,29.3,22.7,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 62 H 85 N6O 10 S6 + 1265.4646, measured value 1265.4637.

[0368] Synthesis of compound (R)-7i

[0369]

[0370] By using preferred acylation reaction conditions, the yellow solid compound (R)-7i (78% yield) was obtained from the deprotected product (R)-6i. f =0.40 (PE / EA = 2 / 1). 1 H NMR(400MHz, CDCl3)δ8.21–7.01(m,12H),3.58–0.79(m,55H).HRMS(ESI+)m / z:[M+H] + Calculated value C 51 H 68 N3O4S3 + 882.4367, measured value 882.4361.

[0371] Synthesis of compound (R)-7j

[0372]

[0373] By using preferred acylation reaction conditions, a pale yellow solid compound of formula (R)-7j (83% yield) was obtained from the deprotected product formula (R)-6j. f =0.25 (PE / EA = 2 / 1). 1 H NMR (500MHz, CDCl3) δ8.09(m,18H),3.19–2.53(m,24H). 13C NMR (126MHz, CDCl3, only major isomer signals in three rotatimers are reported) δ 185.2, 147.6, 146.9, 139.5, 135.5, 133.7, 133.2, 131.7, 130.6, 129.8, 128.9, 128.3, 127.8, 127.3, 126.0, 125.8, 125.1, 42.7, 42.3, 38.1, 38.0. HRMS (ESI+) m / z: [M+H] + Calculated value C 42 H 43 N4O6S4 + 827.2060, measured value 827.2066.

[0374] Synthesis of compound (R)-7k

[0375]

[0376] By using preferred acylation reaction conditions, a white solid compound of formula (R)-7k (76% yield) was obtained from the deprotected product formula (R)-6k. f =0.30 (PE / EA = 1 / 1). 1 H NMR (500MHz, CDCl3) δ9.17–7.34(m,22H),3.21–1.53(m,24H). 13 C NMR (126MHz, CDCl3, only major isomer signals in three rotatores are reported) δ 162.7, 138.6, 135.2, 134.1, 133.6, 133.3, 131.9, 131.1, 129.5, 129.4, 129.1, 128.7, 128.6, 127.8, 126.4, 126.3, 126.1, 124.3, 42.8, 38.8, 38.0, 37.5, 36.6, 31.6. HRMS (ESI+) m / z: [M+H] + Calculated value C 50 H 47 N4O6S4 + 927.2373, measured value 927.2373.

[0377] Synthesis of compound (R)-7l

[0378]

[0379] By using preferred acylation reaction conditions, a white solid compound of formula (R)-7l (51% yield) was obtained from the deprotected product formula (R)-6l. f =0.50 (PE / EA = 10 / 1).1 H NMR (400MHz, CDCl3) δ8.18–7.16(m,18H),3.24–1.96(m,12H). 13 C NMR (101MHz, CDCl3, only major of three rotational isomers for each signal reported) δ185.4,147.1,139.2,133.6,133.1,131.8,130.7,130.2,129.8,129.2,128.5,127.9,126.6,126.1,125.8,124.1,123.0,42.7,37.7. 19 F NMR(376MHz, CDCl3)δ-62.5.IR(neat)2950,1539,1324,1121,805,749,704cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C 40 H 31 F6N2O2S2 + 749.1726, measured value 749.1733.

[0380] Synthesis of compound (R)-7m

[0381]

[0382] By using preferred acylation reaction conditions, a yellow solid compound of formula (R)-7m (61% yield) was obtained from the deprotected product formula (R)-6m. f =0.50 (PE / EA = 30 / 1). 1 H NMR (500MHz, CDCl3) δ8.28–7.28(m,16H),3.23–1.41(m,12H). 13 C NMR (126MHz, CDCl3, only major of three rotational isomers for each signal reported) δ185.0,146.7,140.8,133.4,131.8,131.0,130.4,129.9,128.8,128.3,128.1,127.3,127.0,126.7,126.2,121.5,119.5,42.6,37.3. 19F NMR(471MHz, CDCl3)δ-75.42,-75.45,-75.49,-75.52,-75.54.HRMS(ESI+)m / z:[M+H] + Calculated value C 50 H 29 F 28 N2O2S2 + 1285.1218, measured value 1285.1209.

[0383] (2.5) Step 5:

[0384] Preferably, the rearrangement reaction conditions are as follows: under nitrogen protection, the acylated product (R)-7 obtained in step 4 is stirred at 290°C for 45 minutes. After the reaction is complete, the mixture is cooled to room temperature and purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the rearranged product (R)-8.

[0385] Synthesis of compound (R)-8a

[0386]

[0387] By using preferred rearrangement reaction conditions, a pale yellow solid compound (R)-8a (79% yield) was obtained from the acylated product (R)-7a. f =0.48 (PE / EA = 3 / 2).[α] D 19 .0=-10.8(c=0.25,CHCl3,(R)). 1 H NMR (500MHz, CDCl3) δ8.08(d,J=2.0Hz,2H),7.87(s,2H),7.71(dd,J=7.8,1.9Hz,2H),7.65(s,2H),7.34(d,J=7.9Hz,2H),7.17–7.09(m ,4H),2.84(s,12H),2.72(t,J=7.7Hz,4H),2.68(s,6H),2.45(s,12H),1.65(t,J=7.2Hz,4H),1.35–1.25(m,20H),0.87(t,J=6.8Hz,6H). 13C NMR (126MHz, CDCl3) δ165.4,144.5,142.5,142.2,140.2,136.3,134.9,134.5,133.7,131.8,131.3,131.2,129.1,128.1,127.7,126. 1,126.0,37.2,36.0,31.9,31.1,29.5,29.3,29.3,22.7,20.5,14.1.IR(neat)2930,1666,1455,1322,1160,1090,953,733,589,507cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 60 H 79 N4O6S4 + 1079.4877, measured value 1079.4872.

[0388] Synthesis of compound (R)-8b

[0389]

[0390] By using preferred rearrangement reaction conditions, the acylated product of formula (R)-7b was given as a yellow solid compound of formula (R)-8b (51% yield). f =0.30 (PE / EA = 2 / 1). 1 H NMR(400MHz, CDCl3)δ8.08(s,2H),7.88(s,2H),7.72(d,J=9.7Hz,2H),7.65(s,2H),7.34(d,J=7.9Hz,2H),7.16–7.08(m,4H), 2.84(s,12H),2.73(t,J=7.5Hz,4H),2.68(s,6H),2.45(s,12H),1.68–1.60(m,4H),1.35–1.20(m,52H),0.87(t,J=6.7Hz,6H). 13 C NMR (101MHz, CDCl3) δ165.4,144.5,142.5,142.2,140.2,136.3,134.9,134.5,133.7,131.8,131.3,131.2,129.1,128.1, 127.7,126.1,126.0,37.2,36.0,31.9,31.2,29.7,29.7,29.6,29.5,29.4,29.4,22.7,20.5,14.1.HRMS(APCI+)m / z:[M+H] + Calculated value C76 H 111 N4O6S4 + 1303.7381, measured value 1303.7385.

[0391] Synthesis of compound (R)-8c

[0392]

[0393] By using preferred rearrangement reaction conditions, a white solid compound of formula (R)-8c (30% yield) was obtained from the acylation product of formula (R)-7c. f =0.40 (PE / EA = 3 / 2). 1 H NMR (400MHz, CDCl3) δ8.07(d,J=1.9Hz,2H),7.92(s,2H),7.77(d,J=1.9Hz,2H),7.72(dd,J=7.8,1.9Hz,2H),7.34(td,J=6.6,6.2,3 .0Hz,4H),7.17(d,J=9.0Hz,2H),2.84(s,12H),2.68(s,6H),2.42(s,12H),2.11(s,6H),1.96(d,J=2.9Hz,12H),1.82–1.73(m,12H). 13 C NMR (101MHz, CDCl3) δ165.6,150.5,144.5,142.6,140.4,136.4,135.1,134.7,133.7,131.9,131.4,131 .2,129.8,127.6,126.3,124.9,122.8,68.1,43.1,37.4,36.9,36.6,29.0,20.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 64 H 75 N4O6S4 + 1123.4564, measured value 1123.4562.

[0394] Synthesis of compound (R)-8d

[0395]

[0396] By using preferred rearrangement reaction conditions, a white solid compound of formula (R)-8d (64% yield) was obtained from the acylated product formula (R)-7d. f =0.27 (PE / EA = 2 / 1). 1H NMR(400MHz, CDCl3) δ8.03(d,J=1.8Hz,2H),7.96(s,2H),7.91–7.81(m,4H),7.76(dt,J=7.9,1.5Hz,2H),7.56( t,J=7.8Hz,2H),7.38(dd,J=8.9,2.0Hz,2H),7.18(d,J=9.0Hz,2H),2.74(s,12H),2.45(s,12H),1.37(s,18H). 13 CNMR (101MHz, CDCl3) δ165.5,150.5,144.4,143.3,142.6,134.9,134.6,133.6,131.2,129.9,129.6,128. 0,127.6,126.2,126.2,125.8,122.9,38.2,35.1,31.3.IR(neat)2963,1665,1345,1159,1089,707,584cm -1 .HRMS(APCI+)m / z:[M+H] + Calculated value C 50 H 59 N4O6S4 + 939.3312, measured value 939.3311.

[0397] Synthesis of compounds of formula (R)-8e

[0398]

[0399] By using preferred rearrangement reaction conditions, the pale yellow solid compound (R)-8e (24% yield) was obtained from the acylated product (R)-7e. f =0.48 (PE / EA = 1 / 1). 1 H NMR(500MHz, CDCl3)δ8.07(d,J=1.9Hz,2H),7.97(s,2H),7.90(d,J=8.3Hz,2H) ,7.75(dd,J=7.8,2.0Hz,2H),7.48(ddd,J=8.1,6.5,1.5Hz,2H),7.39(d,J=7.9 Hz,2H),7.30–7.21(m,4H),3.10–2.98(m,4H),2.83(s,12H),2.47(s,12H),1.7 5–1.64(m,4H),1.48–1.33(m,8H),0.92(t,J=6.9Hz,6H).HRMS(ESI+)m / z:[M+H] + Calculated value C 52 H62 N4O6S4 + 967.3625, measured value 967.3601.

[0400] Synthesis of compound (R)-8f

[0401]

[0402] By using preferred rearrangement reaction conditions, the solid compound (R)-8f was obtained from the acylated product (R)-7f (64% yield). f =0.10 (PE / EA = 3 / 1). 1 H NMR (500MHz, CDCl3) δ8.87 (s, 2H), 8.22 (d, J = 7.3Hz, 2H), 8.11 (d, J = 8.2Hz, 2H),7.95(dd,J=16.4,6.1Hz,6H),7.68(s,2H),7.56(t,J=7.9Hz,2H),7.23( d,J=8.7Hz,2H),7.14(d,J=8.8Hz,2H),2.82(s,12H),2.75(t,J=7.9Hz,4H), 2.35(s,12H),1.70–1.63(m,4H),1.40–1.23(m,20H),0.87(t,J=6.7Hz,6H). 13 CNMR (101MHz, CDCl3) δ165.5,144.7,144.2,142.3,142.2,134.1,133.9,133.4,132.9,131.3,130.6,130.2,129.6,128.7,1 28.1,128.0,127.6,126.5,126.4,126.2,124.0,37.6,36.2,32.0,31.3,29.6,29.5,29.4,22.8,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 66 H 79 N4O6S4 + 1151.4877, measured value 1151.4867.

[0403] Synthesis of compound (R)-8g

[0404]

[0405] By using preferred rearrangement reaction conditions, a yellow solid compound of formula (R)-8g (81% yield) was obtained from the acylated product formula (R)-7g. f =0.44 (PE / EA = 2 / 1).1 H NMR (400MHz, CDCl3) δ8.09(s,2H),7.87(s,2H),7.73–7.64(m,4H),7.32(d,J=7.8Hz,2H),7.13(q,J=8.7Hz,4H),3.35(q,J=7.1Hz,8H), 2.72(t,J=7.6Hz,4H),2.66(s,6H),2.45(s,12H),1.70–1.62(m,4H),1.38–1.22(m,20H),1.14(t,J=7.1Hz,12H),0.87(t,J=6.5Hz,6H). 13 C NMR (101MHz, CDCl3) δ165.5,144.6,142.8,142.2,140.2,137.5,136.0,134.3,133.8,131.8,131.3,130.8,129.2,1 28.2,127.8,126.3,126.1,41.2,36.1,32.0,31.2,29.6,29.4,29.3,22.8,20.2,14.2,14.1.HRMS(APCI+)m / z:[M+H] + Calculated value C 64 H 75 N4O6S4 + 1135.5508, measured value 1135.5504.

[0406] Synthesis of compound (R)-8h

[0407]

[0408] By using preferred rearrangement reaction conditions, the acylated product formula (R)-7h was given as a yellow solid compound formula (R)-8h (38% yield). f =0.32 (PE / EA = 1 / 1). 1 H NMR (400MHz, CDCl3) δ8.26(d,J=1.7Hz,4H),8.13(s,2H),7.96(s,2H),7.71(s,2H),7.17(d,J=8.6Hz,2H),7.11(d,J=8.6Hz ,2H),2.79(s,24H),2.74(t,J=7.8Hz,4H),2.49(s,12H),1.67(t,J=7.4Hz,4H),1.37–1.23(m,20H),0.86(t,J=6.1Hz,6H). 13C NMR (126MHz, CDCl3) δ165.0,144.6,144.5,143.0,140.9,136.4,133.8,133.3,131.7,129.7,129.1,12 7.5,126.5,125.3,125.0,38.2,36.1,32.0,31.3,29.6,29.4,29.4,22.8,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 62 H 85 N6O 10 S6 + 1265.4646, measured value 1265.4610.

[0409] Synthesis of compound (R)-8i

[0410]

[0411] By using preferred rearrangement reaction conditions, the white solid compound (R)-8i (53% yield) was obtained from the acylated product (R)-7i. f =0.30 (PE / EA = 2 / 1). 1 H NMR(400MHz, CDCl3)δ8.08(d,J=1.9Hz,1H),7.91–7.85(m,2H),7.77–7.69(m,2H),7.69–7.62(m,2H),7.33(d,J=7.9Hz,1H),7.16–7.07(m,3 H),7.04(d,J=8.7Hz,1H),2.86–2.77(m,12H),2.75–2.66(m,7H),2.38(s,6H),1.72–1.61(m,4H),1.38–1.23(m,20H),0.87(m,J=6.5Hz,6H). 13 C NMR (101MHz, CDCl3) δ166.6,165.5,144.1,142.7,142.3,141.6,141.5,140.3,1 36.4,135.0,134.7,133.9,133.6,133.3,132.0,131.7,131.5,131.4,129.4,128 .5,127.8,127.7,127.5,127.3,127.1,126.4,126.3,126.2,37.4,36.2,36.1,3 2.0,31.3,31.3,29.6,29.5,29.5,29.4,22.8,20.7,14.2.HRMS(ESI+)m / z:[M+H]+ Calculated value C 51 H 68 N3O4S3 + 882.4367, measured value 882.4360.

[0412] Synthesis of compound (R)-8j

[0413]

[0414] By using preferred rearrangement reaction conditions, a yellow solid compound of formula (R)-8j (63% yield) was obtained from the acylated product formula (R)-7j. f =0.20 (PE / EA = 1 / 1). 1 H NMR (500MHz, CDCl3) δ8.05(s,2H),8.00(s,2H),7.92(d,J=8.2Hz,2H),7.87(d,J=7.6Hz,2H),7.77(d,J=7.6Hz ,2H),7.57(t,J=7.8Hz,2H),7.51(t,J=7.3Hz,2H),7.27(dt,J=19.0,8.3Hz,4H),2.75(s,12H),2.47(s,12H). 13 CNMR (126MHz, CDCl3) δ165.1,144.5,142.9,142.5,134.8,134.5,133.5,132.7,129.8,1 29.4,128.0,127.8,127.6,127.2,126.8,126.2,68.0,38.1,25.6.HRMS(ESI+)m / z:[M+H] + Calculated value C 42 H 43 N4O6S4 + 827.2060, measured value 827.2044.

[0415] Synthesis of compound (R)-8k

[0416]

[0417] By using preferred rearrangement reaction conditions, a white solid compound of formula (R)-8k (74% yield) was obtained from the acylated product formula (R)-7k. f =0.22 (PE / EA = 1 / 1). 1H NMR(500MHz, CDCl3)δ8.89(s,2H),8.23(d,J=7.3Hz,2H),8.11(d,J=8.2Hz,2H),8.05(s,2H),7.98–7.9 2(m,6H),7.56(t,J=7.8Hz,2H),7.51(t,J=2.4Hz,2H),7.34–7.28(m,4H),2.82(s,12H),2.35(s,12H). 13 C NMR (126MHz, CDCl3) δ165.1,144.6,144.1,141.8,134.0,133.6,133.3,132.8,132.6,130.5,130.0, 129.9,128.5,128.0,127.7,127.6,127.6,127.4,126.4,126.3,124.0,37.5.HRMS(ESI+)m / z:[M+H] + Calculated value C 50 H 47 N4O6S4 + 927.2373, measured value 927.2372.

[0418] Synthesis of compound (R)-8l

[0419]

[0420] By using preferred rearrangement reaction conditions, but changing the original reaction temperature from 290°C to 250°C and the reaction time from 45 minutes to 80 minutes, while keeping the other operations unchanged, a pale yellow solid compound of formula (R)-8l (71% yield) was finally obtained from the acylated product of formula (R)-7l. f =0.15 (PE / EA = 10 / 1). 1 H NMR (400MHz, CDCl3) δ7.96 (s, 2H), 7.92–7.77 (m, 8H), 7.60 (d, J = 7.8Hz, 2H), 7.55–7.45 (m, 4H), 7.28 (d, J = 2.7Hz, 2H), 2.46 (s, 12H). 13 C NMR (101MHz, CDCl3) δ165.4,144.5,142.7,142.7,133.9,133.6,132.8,129.7 ,129.5,127.9,127.8,127.6,127.2,126.8,125.8,123.7,123.1,36.8,34.4. 19F NMR(376MHz, CDCl3)δ-62.3.IR(neat)2949,1665,1339,1075,896,707,458cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C 40 H 31 F6N2O2S2 + 749.1726, measured value 749.1730.

[0421] Synthesis of compound (R)-8m

[0422]

[0423] By using preferred rearrangement reaction conditions, a solid compound of formula (R)-8m was obtained from the acylated product of formula (R)-7m (22% yield). f =0.18 (PE / EA = 30 / 1). 1 H NMR (500MHz, CDCl3) δ8.05–8.00(m,4H),7.99(s,2H),7.95(d,J=8.2Hz,2H),7.81(s ,2H),7.56–7.51(m,2H),7.32(t,J=7.4Hz,2H),7.22(d,J=8.5Hz,2H),2.46(s,12H). 13 C NMR (126MHz, CDCl3) δ179.0,143.9,141.6,133.5,130.7,130.6,130.0,128.0,127.9,127.4,127.1,127.0,121.8,121.5,119.3,36.1. 19 F NMR(471MHz, CDCl3)δ-75.48,-75.50.HRMS(ESI+)m / z:[M+H] + Calculated value C 50 H 29 F 28 N2O2S2 + 1285.1218, measured value 1285.1177.

[0424] (2.6) Step 6:

[0425] Preferably, the oxidation reaction conditions are as follows: In a round-bottom flask, add the rearranged compound (R)-8 (1.0 equivalent) obtained in step 5 and a mixture of methanol and tetrahydrofuran (volume ratio 1:1, 0.25 mol / L), cool to 0°C, add N-chlorosuccinimide (6.0 equivalent) in batches, then heat to 15°C and stir at this temperature for 30 minutes. Quench the reaction with water, remove as much organic solvent as possible by rotary evaporation under reduced pressure, then extract three times with dichloromethane. Wash the extracted dichloromethane solution with saturated brine, dry with anhydrous sodium sulfate, and remove the solvent by rotary evaporation under reduced pressure. Purify the residue by silica gel column chromatography (eluents: petroleum ether and ethyl acetate) to obtain the oxidation product, a disulfonyl chloride compound (R)-9.

[0426] Synthesis of compound (R)-9a

[0427]

[0428] By using preferred oxidation reaction conditions, a yellow solid compound (R)-9a (99% yield) was obtained from the rearranged product (R)-8a. f =0.25 (PE / EA = 2 / 1).[α] D 19.1 =+42.0(c=0.25,CHCl3,(R)). 1 H NMR (500MHz, CDCl3) δ8.16(d,J=69.0Hz,2H),7.92(s,2H),7.73(s,2H),7.69(d,J=7.8Hz,2H),7.42(d,J=7.9Hz,2H),7.35(d,J=10.1Hz,2H) ,7.09(d,J=8.7Hz,2H),2.83(s,12H),2.79(t,J=7.8Hz,4H),2.72(s,6H),1.69(t,J=7.6Hz,4H),1.40–1.20(m,20H),0.86(t,J=6.8Hz,6H). 13 C NMR (126MHz, CDCl3) δ171.2,146.7,138.9,138.0,137.4,137.3,135.6,135.1,134.9,134.1,132.3,132.2,130.9,130.2, 128.1,126.7,37.2,36.2,32.0,30.9,29.5,29.5,29.3,28.0,22.8,14.2.IR(neat)2923,1382,1160,959,733,560,518cm -1 .HRMS(APCI+)m / z:[M+H] +Calculated value C 54 H 67 Cl2N2O8S4 + 1069.3152, measured value 1069.3148.

[0429] Synthesis of compound (R)-9b

[0430]

[0431] By using preferred oxidation reaction conditions, a yellow solid compound of formula (R)-9b (67% yield) was obtained from the rearrangement product formula (R)-8b. f =0.70 (PE / EA = 2 / 1). 1 H NMR (400MHz, CDCl3) δ8.17(d,J=51.4Hz,2H),7.92(s,2H),7.73(s,2H),7.69(d,J=7.7Hz,2H),7.42(d,J=7.9Hz,2H),7.34(d,J=9.0Hz,2H ),7.09(d,J=8.8Hz,2H),2.83(s,12H),2.78(t,J=7.9Hz,4H),2.73(s,6H),1.75–1.64(m,4H),1.39–1.20(m,52H),0.87(t,J=6.6Hz,6H). 13 C NMR (101MHz, CDCl3) δ146.7,138.9,138.0,137.4,137.3,135.6,135.2,134.9,134.1,132.3,132.1,130.9,130.7,130 .2,128.1,126.7,37.2,36.2,32.1,30.9,29.8,29.8,29.7,29.6,29.5,29.5,22.8,20.7,14.3.HRMS(APCI+)m / z:[M+H] + Calculated value C 70 H 99 Cl2N2O8S4 + 1293.5656, measured value 1293.5659.

[0432] Synthesis of compound (R)-9c

[0433]

[0434] By using preferred oxidation reaction conditions, a white solid compound of formula (R)-9c (99% yield) was obtained from the rearrangement product formula (R)-8c. f =0.70 (PE / EA = 2 / 1).1 H NMR (400MHz, CDCl3) δ8.16(d,J=55.7Hz,2H),7.97(s,2H),7.84(d,J=2.0Hz,2H),7.72–7.65(m,2H),7.57(s,2H),7.42(d, J=7.8Hz,2H),7.12(d,J=9.1Hz,2H),2.82(s,12H),2.72(s,6H),2.13(s,6H),1.97(d,J=3.0Hz,12H),1.86–1.72(m,12H). 13 C NMR (101MHz, CDCl3) δ171.2,154.6,138.8,138.0,137.4,137.3,135.3,135.2,134.8,134.6,132 .3,132.1,130.0,128.0,127.7,123.6,42.8,37.0,36.7,28.8,28.0,20.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 58 H 63 Cl2N2O8S4 + 1113.2839, measured value 1113.2824.

[0435] Synthesis of compound (R)-9d

[0436]

[0437] By using preferred oxidation reaction conditions, a pale yellow solid compound of formula (R)-9d (73% yield) was obtained from the rearrangement product formula (R)-8d. f =0.90 (PE / EA = 2 / 1). 1 H NMR (400MHz, CDCl3) δ8.12–7.98(m,4H),7.94–7.80(m,6H),7.67–7.56(m,4H),7.14(d,J=9.1Hz,2H),2.76(s,12H),1.40(s,18H). 13 C NMR (101MHz, CDCl3) δ171.2,154.7,154.7,140.5,138.8,137.2,135.4,134.9,134.7,134.6,130.0,129 .7,128.4,128.0,127.4,123.7,38.2,31.0,28.0.IR(neat)1963,1735,1342,1159,956,717,559,548cm -1.HRMS(APCI+)m / z:[M+H] + Calculated value C 44 H 47 Cl2N2O8S4 + 929.1587, measured value 929.1584.

[0438] Synthesis of compounds of formula (R)-9e

[0439]

[0440] By using preferred oxidation reaction conditions, the solid compound (R)-9e was obtained from the rearrangement product (R)-8e (96% yield). f =0.78 (PE / EA = 1 / 1). 1 H NMR (400MHz, CDCl3) δ8.26–8.03(m,2H),8.04(s,2H),8.00(d,J=8.3Hz,2H),7.79–7.69(m,4H),7.49(p,J=6.8 ,6.1Hz,4H),7.18(d,J=8.6Hz,2H),2.92(s,16H),1.89–1.55(m,4H),1.52–1.37(m,8H),0.94(t,J=6.9Hz,6H). 13 CNMR (101MHz, CDCl3) δ143.3,139.8,137.3,136.8,135.7,135.2,134.8,134.6,132.3,131.7,131 .0,131.0,129.2,129.1,128.5,128.2,37.2,33.2,32.2,31.5,28.0,22.7.HRMS(ESI+)m / z:[M+H] + Calculated value C 46 H 51 Cl2N2O8S4 + 957.1900, measured value 957.1887.

[0441] Synthesis of compound (R)-9f

[0442]

[0443] By using preferred oxidation reaction conditions, the solid compound (R)-9f was obtained from the rearrangement product (R)-8f (89% yield). f =0.80 (PE / EA = 1 / 1). 1H NMR (500MHz, CDCl3) δ9.05–8.77(m,2H),8.35–8.13(m,4H),8.07–7.97(m,4H),7.91–7.72(m,4H),7.62(q,J=7.7Hz,2H),7.36(d,J=8 .1Hz,2H),7.19(q,J=10.2,8.7Hz,2H),2.79(s,12H),2.73(t,4H),1.69(q,J=8.0Hz,4H),1.34–1.21(m,20H),0.86(t,J=6.8Hz,6H). 13 C NMR (126MHz, CDCl3) δ146.6,146.5,139.4,139.0,137.3,137.0,134.9,134.5,134.3,134.2,133.9,132.8,130.7,130.3,130. 2,129.0,128.3,127.6,126.9,126.3,124.7,37.6,36.3,32.0,30.9,29.6,29.5,29.3,22.8,18.6,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 60 H 67 Cl2N2O8S4 + 1141.3152, measured value 1141.3136.

[0444] Synthesis of compound (R)-9g

[0445]

[0446] By using preferred oxidation reaction conditions, a white solid compound of formula (R)-9 g (75% yield) was obtained from the rearrangement product formula (R)-8 g. f =0.80 (PE / EA = 2 / 1). 1 H NMR (400MHz, CDCl3) δ8.21(d,J=69.8Hz,2H),7.92(s,2H),7.74(s,2H),7.67(d,J=7.0Hz,2H),7.40(d,J=7.9Hz,2H),7.35(d,J=9.1Hz,2H),7.10(d, J=8.8Hz,2H),3.48–3.19(m,8H),2.79(t,J=7.8Hz,4H),2.69(s,6H),1.70 (s,4H),1.41–1.23(m,20H),1.11(t,J=7.1Hz,12H),0.87(t,J=6.5Hz,6H).13 C NMR (101MHz, CDCl3) δ146.6,138.9,138.1,137.6,137.4,137.2,135.7,134.9,134.0,132.0,131.7,130.8,130. 7,130.1,128.1,126.7,40.6,36.2,31.9,30.9,29.5,29.5,29.3,22.8,20.2,14.2,13.6.HRMS(APCI+)m / z:[M+H] + Calculated value C 58 H 75 Cl2N2O8S4 + 1125.3783, measured value 1125.3789.

[0447] Synthesis of compound (R)-9h

[0448]

[0449] By using preferred oxidation reaction conditions, a pale yellow solid compound of formula (R)-9h (63% yield) was obtained from the rearrangement product formula (R)-8h. f =0.84 (PE / EA = 2 / 1). 1 H NMR (500MHz, CDCl3) δ8.26(d,J=12.5Hz,4H),8.18(s,2H),7.96(s,2H),7.79(s,2H),7.41(d,J=8.9Hz, 2H),7.13(d,J=8.8Hz,2H),2.80(m,28H),1.74–1.66(m,4H),1.40–1.21(m,20H),0.86(t,J=6.7Hz,6H). 13 C NMR (126MHz, CDCl3) δ147.3,141.5,138.2,137.2,134.5,133.7,133.4,132.6,131.3,131.3,130.0,127. 9,126.7,126.0,37.9,37.9,37.8,36.0,31.7,30.6,29.2,29.2,29.0,22.5,14.0.HRMS(ESI+)m / z:[M+H] + Calculated value C 56 H 73 Cl2N4O 12 S6 + 1255.2921, measured value 1255.2858.

[0450] Synthesis of compound (R)-9i

[0451]

[0452] By using preferred oxidation reaction conditions, the solid compound (R)-9i was obtained from the rearrangement product (R)-8i (46% yield). f =0.65 (PE / EA = 5 / 1). 1 H NMR (400MHz, CDCl3) δ8.24(d,J=9.0Hz,1H),8.14(d,J=9.0Hz,1H),7.94(s,1H),7.81(s,1H),7.75–7.66(m,2H),7.42(d,J=7.9Hz,1H),7.33(s,1 H),7.29–7.23(m,1H),7.20(d,J=8.7Hz,1H),6.95(d,J=8.8Hz,1H),2.9 1–2.64(m,13H),1.69(m,4H),1.41–1.22(m,20H),0.87(m,J=7.0Hz,6H). 13 C NMR (101MHz, CDCl3) δ146.6,145.9,139.4,138.0,137.2,135.8,135.8,135.5, 135.3,134.9,134.4,134.0,132.2,132.1,130.6,130.6,130.5,130.2,128.2, 128.0,127.0,126.7,123.5,37.2,36.2,36.2,31.9,31.9,30.9,30.8,29.5,29 .5,29.4,29.4,29.3,29.3,29.3,22.8,22.7,20.7,14.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 45 H 56 Cl2NO6S3 + 872.2642, measured value 872.2635.

[0453] Synthesis of compound (R)-9j

[0454]

[0455] By using preferred oxidation reaction conditions, a white solid compound of formula (R)-9j (99% yield) was obtained from the rearrangement product formula (R)-8j. f =0.65 (PE / EA = 1 / 1). 1H NMR (500MHz, CDCl3) δ8.13–7.99(m,6H),7.93–7.82(m,4H),7.77(t,J=7.7Hz,2H ),7.66(t,J=7.9Hz,2H),7.58–7.49(m,2H),7.20(d,J=8.6Hz,2H),2.76(s,12H). 1 H NMR(500MHz,DMSO)δ7.98(d,J=8.1Hz,2H),7.92(s,2H),7.82(d,J=14.4Hz,4H),7.69(d,J=7.7Hz,2H),7 .65(d,J=7.6Hz,2H),7.51(t,J=7.5Hz,2H),7.28(t,J=7.8Hz,2H),6.92(d,J=8.8Hz,2H),2.64(s,12H). 13 C NMR (126MHz, DMSO) δ144.6,138.8,137.0,134.6,133.2,133.1,132.7,131.4,130 .1,129.4,128.2,128.1,128.0,127.7,127.1,125.9,38.3.HRMS(ESI+)m / z:[M+H] + Calculated value C 36 H 31 Cl2N2O8S4 + 817.0335, measured value 817.0330.

[0456] Synthesis of compound (R)-9k

[0457]

[0458] By using preferred oxidation reaction conditions, a white solid compound of formula (R)-9k (99% yield) was obtained from the rearrangement product formula (R)-8k. f =0.51 (PE / EA = 2 / 1). 1 H NMR (500MHz, CDCl3) δ9.07–8.82(m,2H),8.24(d,J=7.3Hz,2H),8.19–8.08(m,4H),8.06–7.98(m,4H),7.86(dd,J=3 4.9,8.7Hz,2H),7.76(s,2H),7.64(t,J=7.7Hz,2H),7.53(d,J=8.0Hz,2H),7.29(m,2H),2.79(s,6H),2.73(s,6H). 13C NMR (126MHz, CDCl3) δ139.4,137.5,137.3,135.1,134.9,134.9,134.7,134.5,134.2,134.1,133.1,132.2,13 1.8,131.3,131.0,130.5,129.3,128.8,128.6,128.0,126.7,125.1,38.4,37.9,37.4.HRMS(ESI+)m / z:[M+H] + Calculated value C 44 H 35 Cl2N2O8S4 + 917.0648, measured value 917.0650.

[0459] Synthesis of compound (R)-9l

[0460]

[0461] By using preferred oxidation reaction conditions, a white solid compound of formula (R)-9l (84% yield) was obtained from the rearrangement product formula (R)-8l. f =0.16 (PE / EA = 10 / 1). 1 H NMR (400MHz, CDCl3) δ8.08–7.98(m,4H),7.90(s,2H),7.82(d,J=7.8Hz,2H),7.75(t ,J=8.0Hz,4H),7.60(t,J=7.8Hz,2H),7.52(t,J=7.6Hz,2H),7.22(d,J=8.7Hz,2H). 13 C NMR (101MHz, CDCl3) δ139.8,139.7,137.4,136.0,134.6,134.6,133.6,131.9,131.0,129.2,128.5,128.2,127.9,127.0,125.1,125.1. 19 FNMR(376MHz, CDCl3)δ-62.5.IR(neat)1387,1310,1125,805,703,528,468cm -1 .HRMS(ESI+)m / z:[M+H] + Calculated value C 34 H 19 C l2 F6O4S2 + 739.0001, measured value 739.0005.

[0462] (2.7) Step 7:

[0463] Preferably, the hydrolysis reaction conditions are as follows: In a round-bottom flask, the oxidation product obtained in step 6, disulfonyl chloride compound (R)-9 (1.0 equivalent), and methanol (0.04 mol / L) are added, followed by the addition of solid sodium hydroxide (50.0 equivalent). The mixture is then heated to 70°C and stirred at this temperature for 5 hours. After the reaction is complete, the temperature is lowered to room temperature, and the pH of the reaction is adjusted to 8 with 1M HCl. The mixture is extracted three times with ethyl acetate. The extracted ethyl acetate solution is washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are ethyl acetate and methanol) to obtain the hydrolysis product, sodium disulfonate compound (R)-10.

[0464] Synthesis of compound (R)-10a

[0465]

[0466] By using preferred hydrolysis reaction conditions, a white solid compound (R)-10a (76% yield) was obtained from the oxidation product (R)-9a. f =0.13(EA / MeOH=10 / 1).[α] D 18.6 = +70.9 (c = 0.25, MeOH, (R)). 1 H NMR (400MHz, CD3OD) δ8.19(s,2H),7.81(d,J=8.2Hz,2H),7.63(s,2H),7.59(s,2H),7.36(d,J=7.9Hz,2H),7.09(d,J=7.1Hz ,2H),7.01(d,J=8.8Hz,2H),2.84(s,12H),2.68(m,10H),1.64(t,J=7.4Hz,4H),1.35–1.23(m,20H),0.87(t,J=6.5Hz,6H). 13 C NMR (101MHz, CD3OD) δ142.1,141.6,138.3,137.0,136.7,135.4,134.8,133.3,132.9,131.8,131.6,131.0,130.3,127.9,127.7 ,125.5,36.4,35.5,31.7,31.0,29.2,29.1,29.0,22.3,19.5,13.1.IR(neat)3445,2930,1459,1159,1036,956,737,588,507cm -1 .HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 70 H98 N2NaO 10 S4 - 1031.3684, measured value 1031.3675.

[0467] Synthesis of compound (R)-10b

[0468]

[0469] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10b (95% yield) was obtained from the oxidation product of formula (R)-9b. f =0.06 (EA / MeOH = 10 / 1). 1 H NMR (400MHz, CD3OD) δ8.17(s,2H),7.80(d,J=7.9Hz,2H),7.61(d,J=15.4Hz,4H),7.36(d,J=7.9Hz,2H),7.08(d,J=8.8Hz,2 H),6.98(d,J=8.8Hz,2H),2.82(s,12H),2.72–2.64(m,10H),1.69–1.57(m,4H),1.37–1.23(m,52H),0.89(t,J=6.6Hz,6H). 13 C NMR (101MHz, CD3OD) δ143.3,143.2,143.1,138.3,138.1,136.9,136.2,134.8,134.4,133.1,133.1,132.4,131.8,129.2,129.1 ,127.0,37.7,36.9,33.1,32.3,30.8,30.8,30.7,30.7,30.7,30.6,30.6,30.5,30.4,23.7,20.8,14.5.HRMS(ESI-)m / z:[M-Na] - Calculated value C 70 H 98 N2NaO 10 S4 - 1277.6007, measured value 1277.6000.

[0470] Synthesis of compound (R)-10c

[0471]

[0472] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10c (60% yield) was obtained from the oxidation product of formula (R)-9c. f =0.10 (EA / MeOH = 10 / 1).1 H NMR (400MHz, CD3OD) δ8.17(s,2H),7.82(d,J=7.8Hz,2H),7.72(d,J=2.0Hz,2H),7.68(s,2H),7.42–7.30(m,4H ),7.02(d,J=9.0Hz,2H),2.83(s,12H),2.68(s,6H),2.08(s,6H),1.99(d,J=3.0Hz,12H),1.85–1.77(m,12H). 13 C NMR (101MHz, CD3OD) δ151.1,143.5,139.8,138.2,137.9,136.8,136.3,134.7,134.2,133.2,132. 9,132.3,132.1,129.1,125.7,123.5,44.1,37.9,37.7,37.4,30.4,20.8.HRMS(ESI-)m / z:[M-Na] - Calculated value C 58 H 62 N2NaO 10 S4 - 1097.3190, measured value 1097.3188.

[0473] Synthesis of compound (R)-10d

[0474]

[0475] By using preferred hydrolysis reaction conditions, a pale yellow solid compound of formula (R)-10d (76% yield) was obtained from the oxidation product formula (R)-9d. f =0.20 (EA / MeOH = 10 / 1). 1 H NMR(500MHz,CD3OD)δ8.15(s,2H),7.96(s,2H),7.80(s,2H),7.74(d,J=7.8Hz,2H),7.70(s,2H), 7.59(t,J=7.7Hz,2H),7.38(d,J=9.1Hz,2H),7.05(d,J=9.1Hz,2H),2.76(s,12H),1.36(s,18H). 13C NMR (126MHz, CD3OD) δ151.0,146.4,139.6,138.3,137.7,136.2,134.4,134.1,132.8,13 2.1,129.0,128.4,126.8,126.6,123.6,79.5,38.6,35.6,31.5.HRMS(ESI-)m / z:[M-Na] - Calculated value C 44 H 46 N2NaO 10 S4 - 913.1938, measured value 913.1931.

[0476] Synthesis of compounds of formula (R)-10e

[0477]

[0478] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10e (81% yield) was obtained from the oxidation product of formula (R)-9e. f =0.72 (EA / MeOH = 10 / 1). 1 H NMR(500MHz,CD3OD)δ8.17(s,2H),7.86(d,J=8.1Hz,4H),7.74(s,2H),7.48–7.39(m,4H),7.23(ddd,J=8.3,6.8,1.3H z,2H),7.08(d,J=8.7Hz,2H),3.04(s,4H),2.82(s,12H),1.79–1.69(m,4H),1.52–1.37(m,8H),0.97(t,J=7.0Hz,6H). 13 C NMR (126MHz, CD3OD) δ143.2,142.0,140.5,138.5,138.1,136.1,134.6,134.4,134.2,133.1,132.2 ,131.5,129.2,128.5,128.1,127.5,37.7,34.3,33.3,32.8,23.6,14.4.HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 46 H 51 N2O 10 S4 - 919.2432, measured value 919.2416.

[0479] Synthesis of compound (R)-10f

[0480]

[0481] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10f was obtained from the oxidation product of formula (R)-9f (85% yield). f =0.18 (EA / MeOH = 10 / 1). 1 H NMR(500MHz,CD3OD)δ8.92(s,2H),8.17(t,J=8.7Hz,4H),8.11–8.01(m,2H),7.96(s,2H),7.71(s,2H),7.63–7.53(m,4 H),7.10(s,4H),2.81(s,12H),2.69(t,J=7.7Hz,4H),1.65(t,J=7.6Hz,4H),1.35–1.23(m,20H),0.87(t,J=6.9Hz,6H). 13 C NMR (126MHz, CD3OD) δ144.0,141.7,138.5,136.8,133.9,133.4,133.0,132.3,131.7,130.4,129.7,128.3,128. 1,127.6,126.5,125.6,123.2,36.7,35.5,31.7,31.0,29.2,29.1,29.0,22.3,13.1.HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 60 H 67 N2O 10 S4 - 1103.3684, measured value 1103.3665.

[0482] Synthesis of compound (R)-10g

[0483]

[0484] By using preferred hydrolysis reaction conditions, a pale yellow solid compound of formula (R)-10g (94% yield) was obtained from the oxidation product formula (R)-9g. f =0.10 (EA / MeOH = 10 / 1). 1H NMR(400MHz,CD3OD)δ8.26(d,J=14.2Hz,2H),7.93–7.81(m,2H),7.75–7.59(m,4H),7.38(d,J=7.8Hz,2H),7.18–6.98(m,4H),3.4 4(q,J=7.1Hz,8H),2.78–2.65(m,10H),1.67(p,J=7.2Hz,4H),1.44–1.28(m,20H),1.20(t,J=7.1Hz,12H),0.91(t,J=6.6Hz,6H). 13 C NMR (101MHz, CD3OD) δ143.3,142.9,139.6,138.4,138.0,137.4,136.3,135.7,134.3,132.9,132.5,132.2,131.6, 129.2,129.0,126.9,42.2,36.9,33.0,32.3,30.5,30.5,30.3,23.7,20.3,14.5,14.4.HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 58 H 75 N2O 10 S4 - 1087.4310, measured value 1087.4297.

[0485] Synthesis of compound (R)-10h

[0486]

[0487] By using preferred hydrolysis reaction conditions, the solid compound formula (R)-10h was obtained from the oxidation product formula (R)-9h (92% yield). f =0.20 (EA / MeOH = 10 / 1). 1 H NMR (500MHz, CD3OD) δ8.37(d,J=60.4Hz,4H),8.07(s,2H),7.73(s,2H),7.68(s,2H),7.17(d,J=8.9Hz,2H),7.06(d,J=8 .8Hz,2H),2.81(s,24H),2.72(t,J=7.7Hz,4H),1.66(dt,J=6.4,3.4Hz,4H),1.39–1.21(m,20H),0.87(t,J=6.9Hz,6H). 13C NMR (126MHz, CD3OD) δ147.7,143.2,139.3,137.5,136.6,135.9,134.7,134.0,133.1,131.4,129 .4,129.0,126.9,125.8,38.3,36.7,32.8,32.1,30.4,30.3,30.2,23.5.HRMS(ESI-)m / z:[M-Na] - Calculated value C 56 H 72 N4NaO 14 S6 - 1239.3272, measured value 1239.3236.

[0488] Synthesis of compound (R)-10i

[0489]

[0490] By using preferred hydrolysis reaction conditions, the solid compound (R)-10i was obtained from the oxidation product (R)-9i (55% yield). f =0.15(EA / MeOH=10 / 1).HRMS(ESI-)m / z:[M-Na] - Calculated value C 45 H 55 NNaO8S3 - 856.2992, measured value 856.2999.

[0491] Synthesis of compound (R)-10j

[0492]

[0493] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10j (82% yield) was obtained from the oxidation product of formula (R)-9j. f =0.70 (EA / MeOH = 5 / 1). 1 H NMR (500MHz, CD3OD) δ8.17(s,2H),7.98(s,2H),7.89(d,J=8.1Hz,2H),7.76(d,J=6.4Hz,4H),7.61( t,J=7.8Hz,2H),7.48(t,J=7.5Hz,2H),7.26(t,J=7.9Hz,2H),7.12(d,J=8.5Hz,2H),2.78(s,12H). 13C NMR (126MHz, CD3OD) δ146.1,140.2,138.3,137.8,136.1,134.4,134.3,133.9,131.9 ,130.8,129.0,128.4,128.2,128.0,127.4,126.7,38.4.HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 36 H 31 N2O 10 S4 - 779.0867, measured value 779.0870.

[0494] Synthesis of compound (R)-10k

[0495]

[0496] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10k (80% yield) was obtained from the oxidation product of formula (R)-9k. f =0.70 (EA / MeOH = 2 / 1). 1 H NMR (400MHz, CD3OD) δ8.52(d,J=4.2Hz,2H),7.61(d,J=7.4Hz,2H),7.54(s,2H),7.49(d,J=8.3Hz,2H),7.40(s,4H),7.36(d,J=8.1Hz, 2H),6.95(t,J=7.7Hz,2H),6.82(t,J=7.1Hz,2H),6.79–6.73(m,2H),6.68(d,J=8.8Hz,2H),2.22(s,12H).HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 44 H 35 N2O 10 S4 - 879.1180, measured value 879.1155.

[0497] Synthesis of compound (R)-10l

[0498]

[0499] By using preferred hydrolysis reaction conditions, a white solid compound of formula (R)-10l (99% yield) was obtained from the oxidation product of formula (R)-9l. f =0.20 (EA / MeOH = 10 / 1). 1H NMR (400MHz, CD3OD) δ7.24(s,2H),7.18(d,J=7.8Hz,2H),7.06(d,J=8.2Hz,2H),6.95(s,2H),6.85(d,J=7.9H z,2H),6.74(t,J=7.8Hz,2H),6.66(t,J=7.5Hz,2H),6.43(td,J=7.1,6.7,3.4Hz,2H),6.34(d,J=8.6Hz,2H). 13 C NMR (101MHz, CD3OD) δ145.8,140.1,138.6,137.9,135.3,134.4,134.1,132.3,130.1,129.8,129.1,128.5,128.3,128.2,127.6,124.0. 19 F NMR(376MHz,CD3OD)δ-63.2.HRMS(ESI-)m / z:[M-Na] - Calculated value C 34 H 18 F6NaO6S2 - 723.0352, measured value 723.0353.

[0500] (2.8) Step 8:

[0501] Preferably, the acidification conditions are as follows: the hydrolysis product sodium disulfonate compound (R)-10 obtained in step 7 is dissolved in methanol, and then the methanol solution is passed through a cation exchange resin Amberlyst 15 (10 cm⁻¹). 3 / 200mg of formula (R)-10) was eluted twice with methanol, and the methanol in the solution was removed by rotary evaporation under reduced pressure. The resulting solid was then dried under vacuum at 50°C for 6 hours to obtain the final product, chiral binaphthyl disulfonic acid formula (R)-1.

[0502] Synthesis of compound (R)-1a

[0503]

[0504] By using preferred acidification conditions, a pale yellow solid compound (R)-1a (99% yield) was obtained from the hydrolysis product (R)-10a. [α] D 18.0 = +62.9 (c = 0.11, MeOH, (R)). 1H NMR (500MHz, CD3OD) δ8.10(s,2H),7.75–7.69(m,4H),7.67(s,2H),7.39(d,J=7.8Hz,2H),7.15(d,J=8.4Hz,2H),7.01(d,J=8. 4Hz,2H),2.82(s,12H),2.71(t,J=7.8Hz,4H),2.68(s,6H),1.65(t,J=7.5Hz,4H),1.35–1.25(m,20H),0.87(t,J=6.7Hz,6H). 13 C NMR (126MHz, CD3OD) δ142.7,141.1,137.1,136.7,136.3,135.9,134.3,133.9,133.4,131.4,131. 3,131.2,130.9,128.2,127.7,125.8,36.3,35.5,31.6,30.9,29.2,29.1,29.0,22.3,19.4,13.1. 1 H NMR (400MHz, CDCl3) δ7.94(s,2H),7.71(s,2H),7.60(s,6H),7.15(d,J=8.9Hz,2H),6.98(d,J=8.8Hz,2H),2.8 0–2.63(m,16H),2.57(s,6H),1.64(t,J=7.6Hz,4H),1.30(m,J=23.2,11.1,5.8Hz,20H),0.87(t,J=6.5Hz,6H). 13 C NMR (101MHz, CDCl3) δ143.9,140.3,137.5,136.9,136.1,134.6,134.3,133.9,133.5,132.3,131.9,131.2,130.0,129.5,128.0 ,126.2,37.3,36.1,32.0,31.0,29.6,29.6,29.4,22.8,20.6,14.2.IR(neat)3441,2930,1315,1139,1033,952,737,589,508cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 70 H 99 N2O 10 S4 - 1031.3684, measured value 1031.3678.

[0505] Synthesis of compound (R)-1b

[0506]

[0507] By using preferred acidification conditions, a brown solid compound of formula (R)-1b (94% yield) was obtained from the hydrolysis product formula (R)-10b. [α] D 18.3 = +10.9 (c = 1.01, MeOH, (R)). 1 H NMR (400MHz, CD3OD) δ8.11(s,2H),7.73–7.62(m,4H),7.58(s,2H),7.36(d,J=7.8Hz,2H),7.09(d,J=8.9Hz,2H),7.0 3(d,J=8.9Hz,2H),2.81(s,12H),2.72–2.58(m,10H),1.68–1.52(m,4H),1.39–1.14(m,52H),0.87(t,J=6.5Hz,6H). 13 C NMR (101MHz, CD3OD) δ143.9,142.4,138.5,138.1,137.7,137.2,135.6,135.3,134.7,132.7,132.6,132.3,129.6,129.1,127.2,79.5 ,37.7,36.9,33.1,32.3,30.9,30.8,30.8,30.8,30.7,30.6,30.5,30.5,23.8,20.8,14.6.IR(neat)3388,2922,1465,1143,738,594cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 70 H 99 N2O 10 S4 - 1255.6188, measured value 1255.6179.

[0508] Synthesis of compound (R)-1c

[0509]

[0510] By using preferred acidification conditions, a gray solid compound of formula (R)-1c (99% yield) was obtained from the hydrolysis product formula (R)-10c. [α] D 18.4 = +52.9 (c = 0.21, MeOH, (R)). 1H NMR(500MHz,CD3OD)δ8.11(s,2H),7.73(dd,J=24.4,8.3Hz,6H),7.42–7.36(m,4H),7.03(d, J=9.1Hz,2H),2.83(s,12H),2.68(s,6H),2.06(s,6H),1.97(s,12H),1.79(m,J=9.7Hz,12H). 13 C NMR (126MHz, CD3OD) δ152.1,142.5,138.3,137.9,137.8,137.3,135.7,135.2,134.6,132.8,132.6,128.9 ,126.4,123.8,44.0,37.8,37.7,37.5,30.4,30.3,20.8.IR(neat)3341,2904,1318,1139,903,734,590cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 58 H 63 N2O 10 S4 - 1075.3371, measured value 1075.3372.

[0511] Synthesis of compound (R)-1d

[0512]

[0513] By using preferred acidification conditions, a brown solid compound of formula (R)-1d (97% yield) was obtained from the hydrolysis product formula (R)-10d. [α] D 18.7 = +72.0 (c = 0.25, CHCl3, (R)). 1 H NMR (400MHz, CD3OD) δ8.08(s,2H),7.87(d,J=12.8Hz,4H),7.77(d,J=14.2Hz,4H),7.61(t ,J=7.8Hz,2H),7.43(d,J=9.2Hz,2H),7.06(d,J=9.2Hz,2H),2.74(s,12H),1.36(s,18H). 13C NMR (101MHz, CD3OD) δ152.0,145.5,138.2,138.0,137.9,135.9,134.9,134.5,132.7,132.6,130.8,128.9 ,128.7,127.1,123.9,79.5,38.6,35.7,31.5.IR(neat)3440,2967,1475,1335,1153,949,710,584,518cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 44 H 47 N2O 10 S4 - 891.2119, measured value 891.2115.

[0514] Synthesis of compounds of formula (R)-1e

[0515]

[0516] By using preferred acidification conditions, a brown solid compound of formula (R)-1e (86% yield) was obtained from the hydrolysis product formula (R)-10e. [α] D 22.7 =+45.5(c=0.15,MeOH,(R)). 1 H NMR (500MHz, CD3OD) δ8.10(s,2H),7.91(d,J=8.2Hz,2H),7.82(s,2H),7.77(d,J=7.9Hz,2H),7.51(t,J=7.4Hz,2H),7.45(d,J=7.8Hz,2H ),7.28(t,J=7.8Hz,2H),7.10(d,J=8.7Hz,2H),3.04(s,4H),2.81(s,12H),1.78–1.69(m,4H),1.47–1.39(m,8H),0.96(t,J=6.8Hz,6H). 13 C NMR (126MHz, CD3OD) δ142.5,142.2,138.7,138.5,138.2,135.7,134.9,134.5,134.3,132.8,132.7,131.8,129.0 ,128.9,128.8,128.0,37.7,34.3,33.3,32.8,23.6,14.4.IR(neat)3436,2932,1698,1310,1125,1029,752,590cm -1 .HRMS(ESI-)m / z:[MH]- Calculated value C 46 H 51 N2O 10 S4 - 919.2432, measured value 919.24321.

[0517] Synthesis of compound (R)-1f

[0518]

[0519] By using preferred acidification conditions, a yellowish-brown solid compound of formula (R)-1f was obtained from the hydrolysis product formula (R)-10f (89% yield). [α] D 18.0 = +77.4 (c = 0.12, MeOH, (R)). 1 H NMR (500MHz, CD3OD) δ8.90(s,2H),8.20(d,J=7.0Hz,4H),7.96(s,4H),7.78(s,2H),7.67(s,2H),7.60(t,J=7.8Hz,2H),7.17(d ,J=8.6Hz,2H),7.11(s,2H),2.78(s,12H),2.71(t,J=7.8Hz,4H),1.70–1.61(m,4H),1.35–1.24(m,20H),0.86(t,J=6.8Hz,6H). 13 C NMR (126MHz, CD3OD) δ143.1,142.8,138.2,137.3,136.3,134.0,133.5,133.4,132.3,131.4,131.2,130.1,130.0,128.4,128.2,1 27.8,126.6,125.8,125.2,123.5,36.5,35.5,31.6,30.9,29.2,29.1,29.0,22.3,13.1.IR(neat)3463,1324,1133,838,721,584cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 60 H 67 N2O 10 S4 - 1103.3684, measured value 1103.3661.

[0520] Synthesis of compound of formula (R)-1g

[0521]

[0522] By using preferred acidification conditions, a reddish-brown solid compound of formula (R)-1g (99% yield) was obtained from the hydrolysis product formula (R)-10g. [α] D 18.4 =+44.1(c=0.25,MeOH,(R)). 1 H NMR (400MHz, CD3OD) δ8.10(s,2H),7.75–7.65(m,6H),7.38(d,J=7.7Hz,2H),7.15(d,J=8.9Hz,2H),7.00(d,J=8.8Hz,2H),3.41–3.33(q, 8H),2.72(t,J=7.6Hz,4H),2.66–2.63(m,6H),1.70–1.62(m,4H),1.29(t,J=9.7,0.2Hz,20H),1.18–1.09(t,12H),0.87(t,J=8.4Hz,6H). 13 C NMR (101MHz, CD3OD) δ144.0,142.4,138.6,138.3,137.9,137.8,136.8,135.2,134.8,132.8,132.5,132.3,132.1,129.5,129.1 ,127.2,42.6,36.9,33.0,32.3,30.6,30.5,30.4,23.7,20.3,14.5,14.4.IR(neat)3431,2939,1297,1143,1016,919,782,591cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 58 H 75 N2O 10 S4 - 1087.4310, measured value 1087.4299.

[0523] Synthesis of compounds of formula (R)-1h

[0524]

[0525] By using preferred acidification conditions, a yellowish-brown solid compound of formula (R)-1h (86% yield) was obtained from the hydrolysis product formula (R)-10h. [α] D 18.0 = +68.4 (c = 0.11, MeOH, (R)). 1H NMR (500MHz, CD3OD) δ8.27(d,J=16.7Hz,4H),8.08(s,2H),7.81(s,2H),7.73(s,2H),7.22(d,J=8.1Hz,2H),7.08(d,J =8.8Hz,2H),2.78(s,24H),2.73(t,J=7.7Hz,4H),1.71–1.63(m,4H),1.30(d,J=26.9Hz,20H),0.87(t,J=6.7Hz,6H). 13 C NMR (126MHz, CD3OD) δ147.0,144.3,138.1,137.8,136.5,136.5,134.6,134.5,133.0,132.1,130.1,129.0,127.4, 126.2,38.5,36.9,33.0,32.3,30.5,30.5,30.3,23.7,14.4.IR(neat)3446,2929,1351,1156,954,824,707,574cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 56 H 73 N4O 14 S6 - 1217.3453, measured value 1217.3423.

[0526] Synthesis of compounds of formula (R)-1i

[0527]

[0528] By using preferred acidification conditions, a brown solid compound of formula (R)-1i (99% yield) was obtained from the hydrolysis product formula (R)-10i. 1 H NMR (400MHz, CD3OD) δ8.10(d,J=8.5Hz,1H),7.95(d,J=8.9Hz,1H),7.72(d,J=12.8Hz,3H),7.65–7.62(m,1H),7.39(d,J=7.8Hz,1H),7.14(d,J=8. 8Hz,1H),7.07(d,J=8.8Hz,2H),6.84(d,J=8.8Hz,1H),2.82(s,6H),2.76 –2.64(m,7H),1.70–1.58(m,4H),1.40–1.22(m,20H),0.93–0.82(m,6H). 13C NMR (101MHz, CD3OD) δ144.2,143.4,142.4,138.4,138.0,137.3,137.2,137.1,13 5.7,135.6,135.4,134.8,133.3,132.8,132.7,132.7,132.6,130.8,129.5,129. 3,129.2,129.0,128.6,127.3,127.1,125.5,37.7,36.9,36.8,33.0,33.0,32.3, 32.2,30.6,30.5,30.5,30.4,30.3,30.3,23.7,20.8,14.4.HRMS(ESI-)m / z:[MH] - Calculated value C 45 H 56 NO8S3 - 834.3173, measured value 834.3184.

[0529] Synthesis of compound (R)-1j

[0530]

[0531] By using preferred acidification conditions, a brown solid compound of formula (R)-1j was obtained from the hydrolysis product of formula (R)-10j (94% yield). 1 H NMR(500MHz,CD3OD)δ8.06(s,2H),7.91(d,J=8.2Hz,2H),7.87(d,J=7.5Hz,2H),7.82(s,2H),7.74(d,J=7.9Hz ,2H),7.60(t,J=7.7Hz,2H),7.51(t,J=7.4Hz,2H),7.29(t,J=7.3Hz,2H),7.10(d,J=8.0Hz,2H),2.72(s,12H). 13 C NMR (126MHz, CD3OD) δ144.1,137.0,136.8,134.5,133.5,133.0,133.0,131.3 ,129.4,127.7,127.5,127.4,127.3,126.7,125.8,37.2.HRMS(ESI-)m / z:[MH] - Calculated value C 36 H 31 N2O 10 S4 - 779.0867, measured value 779.0869.

[0532] Synthesis of compounds of formula (R)-1k

[0533]

[0534] By using preferred acidification conditions, a brown solid compound of formula (R)-1k was obtained from the hydrolysis product of formula (R)-10k (98% yield). 1 H NMR(500MHz,CD3OD)δ8.92(s,2H),8.23(d,J=8.2Hz,2H),8.16(s,2H),8.01(s,4H),7.87(d,J=8.1Hz,2H),7.81( s,2H),7.62(t,J=7.8Hz,2H),7.47(t,J=7.5Hz,2H),7.25(t,J=7.8Hz,2H),7.13(d,J=8.7Hz,2H),2.82(s,13H). 13 C NMR (126MHz, CD3OD) δ140.0,135.5,135.0,134.8,134.3,133.9,132.3,129.8,129.5,128.7,128.3,127.6,124.9,38.2.HRMS(ESI-)m / z:[MH] - Calculated value C 44 H 35 N2O 10 S4 - 879.1180, measured value 879.1175.

[0535] Synthesis of compound (R)-1l

[0536]

[0537] By using preferred acidification conditions, a brown solid compound of formula (R)-1l (92% yield) was obtained from the hydrolysis product formula (R)-10l. [α] D 18.5 = +77.4 (c = 0.19, MeOH, (R)). 1 H NMR (400MHz, CD3OD) δ7.95–7.84(m,6H),7.82(s,2H),7.64(d,J=7.9Hz,2H),7.54(dt,J=14.8,7.7Hz,4H),7.29(t,J=7.8Hz,2H),7.12(d,J=8.7Hz,2H). 13C NMR (101MHz, CD3OD) δ145.1,138.6,138.4,135.0,134.5,134.3,132.8,130.3,130.0,129.0,128.9,128.8,128.5,128.1,127.4,124.4. 19 F NMR(376MHz,CD3OD)δ-63.8.IR(neat)3337,1338,1122,1029,807,704,673,550cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 34 H 19 F6O6S2 - 701.0532, measured value 701.0536.

[0538] Synthesis of compounds of formula (R)-1m

[0539]

[0540] Since the rearrangement product (R)-8m cannot be successfully oxidized to (R)-9m using the preferred oxidation conditions, a method is provided here to directly oxidize the final disulfonic acid product (R)-1m from (R)-8m. Preferably, the specific steps are as follows: Compound (R)-8m (55.0 mg, 0.04 mmol) and 1 mL of dichloromethane are added to a 10 mL round-bottom flask, followed by the sequential addition of 1.5 mL of formic acid and hydrogen peroxide (145.6 mg, 1.3 mmol). The mixture is stirred at room temperature for 10 hours. After the reaction is complete, the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluent: dichloromethane:methanol = 20:1). The resulting solid is acidified with concentrated hydrochloric acid, and the residual water is removed by azeotropic heating with toluene. The solid is then dried under vacuum at 50 °C to obtain a grayish-white solid compound (R)-1m (35.9 mg, 72% yield). [α] D 22.7 = +37.6 (c = 0.26, MeOH, (R)). 1 H NMR (500MHz, CD3OD) δ8.24(s,4H),7.95(d,J=8.1Hz,2H),7.81(s,4H),7.53(t,J=7.4Hz,2H),7.37–7.31(m,2H),7.09(d,J=8.7Hz,2H). 13C NMR (126MHz, CD3OD) δ147.2,137.8,136.7,134.5,134.4,134.3,132.8,131.0,129.0,128.9,128.8,128.5,126.2,121.8. 19 F NMR(471MHz,CD3OD)δ-76.70,-76.94,-76.98,-77.01,-77.06.HRMS(ESI-)m / z:[MH] - Calculated value C 44 H 17 F 28 O6S2 - 1237.0024, measured value 1237.0015.

[0541] Example 3

[0542] This embodiment describes the preparation method of compounds of formula (R)-2a,2b,2c, which consists of 3 steps. The synthetic route is as follows:

[0543]

[0544] Includes the following steps:

[0545] (3.1) Step 1:

[0546] Preferably, the nitrogen-sulfur bond breaking reaction conditions are as follows: Under nitrogen protection, the hydrolysis product (R)-10 (1.0 equivalent) obtained in step 7 of Example 2 is added to a round-bottom flask. After cooling to 0°C, methyl trifluoromethanesulfonate (160.0 equivalent) is slowly added. After the addition is complete, the temperature is raised to 100°C and stirring is continued for 20 hours. After cooling to room temperature, an appropriate amount of water is added and the mixture is stirred at room temperature for 1 hour. Then, an appropriate amount of saturated ammonium chloride aqueous solution is added, and the mixture is extracted three times with dichloromethane. The extracted dichloromethane solution is washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are petroleum ether and ethyl acetate) to obtain the tetrabasic methyl sulfonate compound (R)-11.

[0547] Synthesis of compound (R)-11a

[0548]

[0549] By using preferred nitrogen-sulfur bond cleavage reaction conditions, a yellow solid compound (R)-11a (81% yield) was obtained from the hydrolysis product (R)-10a. f =0.48 (PE / EA = 1 / 1). 1H NMR (500MHz, CDCl3) δ8.20(s,2H),7.86(s,2H),7.75(s,2H),7.70(d,J=1.7Hz,2H),7.44(d,J=7.9Hz,2H),7.30(d,J=8.9Hz,2H),7.13(d,J=8.8Hz, 2H),3.78(s,6H),3.40(s,6H),2.80–2.74(m,4H),2.72(s,6H),1.73–1.65 (m,4H),1.46–1.14(m,20H),0.87(t,J=6.9Hz,6H).HRMS(ESI+)m / z:[M+H] + Calculated value C 54 H 67 O 12 S4 + 1035.3510, measured value 1035.3572.

[0550] Synthesis of compound (R)-11b

[0551]

[0552] By using preferred nitrogen-sulfur bond cleavage reaction conditions, a pale yellow solid compound of formula (R)-11b (99% yield) was obtained from the hydrolysis product of formula (R)-10j. f =0.71 (PE / EA = 1 / 1). 1 H NMR(500MHz, CDCl3)δ8.16(s,2H),8.03–7.94(m,6H),7.89(s,2H),7.68(dt,J= 20.2,7.7Hz,4H),7.50(s,2H),7.23(d,J=8.6Hz,2H),3.82(s,6H),3.40(s,6H). 13 C NMR (126MHz, CDCl3) δ141.6,138.9,135.3,133.9,133.0,132.4,131.9,129.9,128.6,128.2,127.4,127.3,29.3,27.2.HRMS(ESI+)m / z:[M+H] + Calculated value C 36 H 31 O 12 S4 + 783.0693, measured value 783.0693.

[0553] Synthesis of compound (R)-11c

[0554]

[0555] By using preferred nitrogen-sulfur bond cleavage reaction conditions, a yellow solid compound of formula (R)-11c (74% yield) was obtained from the hydrolysis product of formula (R)-10k. f =0.21 (PE / EA = 1 / 1). 1 H NMR (500MHz, CDCl3) δ8.79(s,2H),8.35(d,J=7.3Hz,2H),8.22(d,J=8.2Hz,2H),8.11–7.86(m,8H),7.69(t,J=7.4Hz ,2H),7.63(t,J=7.8Hz,2H),7.51(t,J=7.8Hz,2H),7.32(d,J=9.1Hz,2H),3.76(d,J=10.6Hz,6H),3.65–3.32(m,6H). 13 C NMR (126MHz, CDCl3) δ141.4,141.1,137.2,135.5,133.6,133.2,132.4,131.4,131.2,13 0.5,129.8,128.5,128.4,127.6,125.5,124.6,124.5,56.8,56.5.HRMS(ESI+)m / z:[M+H] + Calculated value C 44 H 35 O 12 S4 + 883.1006, measured value 883.0999.

[0556] (3.2) Step 2:

[0557] Preferably, the hydrolysis reaction conditions are as follows: In a round-bottom flask, the tetrabasic methyl sulfonate compound (R)-11 (1.0 equivalent) obtained in step 1 and methanol (0.05 mol / L) are added, followed by the addition of solid sodium hydroxide (50.0 equivalent). The mixture is then heated to 70°C and stirred at this temperature for 5 hours. After the reaction is complete, the temperature is lowered to room temperature, and the pH of the reaction is adjusted to 8 using a 2M HCl methanol solution. The solvent is then removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are ethyl acetate and methanol) to obtain the hydrolysis product, sodium tetrabasic sulfonate compound (R)-12.

[0558] Synthesis of compound (R)-12a

[0559]

[0560] By using preferred hydrolysis reaction conditions, a yellowish-brown solid compound (R)-12a (99% yield) was obtained from the nitrogen-sulfur bond cleavage product (R)-11a.f =0.30 (EA / MeOH = 1 / 1). 1 H NMR (400MHz, CD3OD) δ8.21(d,J=2.0Hz,2H),7.70–7.61(m,4H),7.58(s,2H),7.24(d,J=7.9Hz,2H),7.06(dd,J=8.8,1.8Hz,2H), 6.94(d,J=8.8Hz,2H),2.75–2.65(m,10H),1.67–1.60(m,4H),1.35–1.24(m,20H),0.87(t,J=6.6Hz,6H).HRMS(ESI-)m / z:[M-Na] - Calculated value C 50 H 54 Na3O 12 S4 - 1043.2196, measured value 1043.2240.

[0561] Synthesis of compound (R)-12b

[0562]

[0563] By using preferred hydrolysis reaction conditions, a brown solid compound of formula (R)-12b (99% yield) was obtained from the nitrogen-sulfur bond cleavage product of formula (R)-11b. f =0.24 (EA / MeOH = 3 / 7). 1 H NMR(500MHz,CD3OD)δ8.16(s,2H),7.88(d,J=8.2Hz,2H),7.82(d,J=7.9Hz,3H),7.79(s,2H) ,7.74(d,J=7.6Hz,2H),7.47(q,J=7.1Hz,4H),7.22(t,J=7.7Hz,2H),7.02(d,J=8.7Hz,2H). 13 C NMR (126MHz, CD3OD) δ143.5,142.7,137.7,136.7,133.1,132.9,131.0,127.8,127.3,127.1,126.6,126.3,123.6.HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 32 H 19 Na2O 12 S4 - 768.9560, measured value 768.9272.

[0564] Synthesis of compound (R)-12c

[0565]

[0566] By using preferred hydrolysis reaction conditions, a brown solid compound of formula (R)-12c (99% yield) was obtained from the nitrogen-sulfur bond cleavage product of formula (R)-11c. f =0.36 (EA / MeOH = 1 / 2). 1 H NMR(500MHz,CD3OD)δ8.97(s,2H),8.20(d,J=7.4Hz,2H),8.07–8.00(m,2H),7.96(s,2H),7. 93–7.81(m,6H),7.48(dt,J=15.0,7.7Hz,4H),7.22(d,J=7.9Hz,2H),7.09(d,J=7.1Hz,2H). 13 C NMR (126MHz, CD3OD) δ143.6,141.8,140.5,140.5,138.6,135.0,134.9,134.6,132.8,131.1 ,131.0,129.6,129.0,128.3,128.0,127.4,127.3,125.5,80.0.HRMS(ESI-)m / z:[M-2Na+H] - Calculated value C 40 H 23 Na2O 12 S4 - 868.9873, measured value 868.9876.

[0567] (3.3) Step 3:

[0568] Preferably, the acidification conditions are as follows: the sodium tetrasulfonate compound (R)-12, the hydrolysis product obtained in step 2, is dissolved in water, and then the aqueous solution is passed through a cation exchange resin Amberlyst 15 (10 cm⁻¹). 3 The product (200 mg of hydrolysate) was washed twice with water. The water in the system was removed by heating with toluene to a boil. The resulting solid was then vacuum dried at 50 °C for 6 hours to obtain the final product, chiral binaphthyl tetrasulfonic acid (R)-2a-c.

[0569] Synthesis of compound (R)-2a

[0570]

[0571] By using preferred acidification conditions, a brown solid compound (R)-2a (99% yield) was obtained from the hydrolysis product (R)-12a. [α] D 18.0= +53.0 (c = 0.10, MeOH, (R)). 1 H NMR(500MHz,CD3OD)δ8.17(s,2H),7.72–7.59(m,6H),7.26(d,J=7.7Hz,2H),7.11(d,J=8.8Hz,2H),6. 97(d,J=8.9Hz,2H),2.76–2.67(m,10H),1.70–1.60(m,4H),1.35–1.26(m,20H),0.87(t,J=6.6Hz,6H). 13 C NMR (126MHz, CD3OD) δ142.2,141.0,140.6,137.7,137.0,134.3,133.3,132.2,131.4,130.9,129.8,128.5,127.8 ,127.7,125.6,35.5,31.6,31.0,29.2,29.1,29.0,22.3,19.1,13.0.IR(neat)3422,2929,1468,1163,1019,608cm -1 .HRMS(ESI-)m / z:[MH] - Calculated value C 50 H 57 O 12 S4 - 977.2738, measured value 977.2722.

[0572] Synthesis of compound (R)-2b

[0573]

[0574] By using preferred acidification conditions, a brown solid compound of formula (R)-2b was obtained from the hydrolysis product of formula (R)-12b (99% yield). 1 H NMR (500MHz, CD3OD) δ8.08(s,2H),7.92(d,J=8.2Hz,2H),7.84(d,J=7.3Hz,4H),7.80(d,J=7.9Hz ,2H),7.52(t,J=7.6Hz,2H),7.46(t,J=7.7Hz,2H),7.29(t,J=7.5Hz,2H),7.10(d,J=8.6Hz,2H). 13C NMR (126MHz, CD3OD) δ144.6,144.2,138.9,134.4,134.2,133.7,132.8,129.9, 129.2,129.0,128.8,128.7,128.6,127.8,127.8,125.2.HRMS(ESI-)m / z:[MH] - Calculated value C 32 H 21 O 12 S4 - 724.9921, measured value 724.9915.

[0575] Synthesis of compound (R)-2c

[0576]

[0577] By using preferred acidification conditions, a brown solid compound of formula (R)-2c was obtained from the hydrolysis product of formula (R)-12c (99% yield). 1 H NMR (500MHz, CD3OD) δ9.40–8.45(m,2H),8.20(d,J=7.2Hz,2H),8.11–7.86(m,10H),7.51(dq,J=21.2,13.1,10.3Hz,4H),7.37–6.92(m,4H). 13 C NMR (126MHz, CD3OD) δ142.2,140.0,138.5,137.5,133.4,133.3,131.1,128.6,128.5,128 .0,127.8,127.5,126.4,126.1,125.9,125.6,124.9,124.0,123.6.HRMS(ESI-)m / z:[MH] - Calculated value C 40 H 25 O 12 S4 - 825.0234, measured value 825.0233.

[0578] Example 4

[0579] This embodiment describes the preparation method of compound (R)-2d,2e,2f, which consists of two steps. The synthetic route is as follows:

[0580]

[0581] Includes the following steps:

[0582] (4.1) Step 1:

[0583] Preferably, the coupling reaction conditions are as follows: under nitrogen protection, the halogenated product (R)-4 (1.0 equivalent) obtained in step 1 of Example 2, the borate ester compound (15g-i) containing SO3Et groups obtained in step 2 of Example 1 (3.5 equivalent), tetrakis(triphenylphosphine)palladium (0.1 equivalent), potassium carbonate (3.5 equivalent), and N,N-dimethylformamide (to make the concentration of (R)-4 0.1 mol / L) are added sequentially to a three-necked flask equipped with a reflux condenser. The resulting mixture is stirred at 60°C for 12 hours. After the reaction is complete, the temperature is lowered to room temperature, and the solvent is removed by rotary evaporation under reduced pressure. The residue is purified by silica gel column chromatography (eluents are ethyl acetate and methanol) to obtain the coupling product, potassium disulfonate compound (R)-5m-o.

[0584] Synthesis of compound (R)-5m

[0585]

[0586] By using preferred coupling reaction conditions, a white solid compound (R)-5m (35% yield) was obtained from the halogenated product (R)-4a and the arylboronic ester compound (R)-15g. f =0.54 (EA / MeOH = 5 / 1). 1 H NMR (400MHz, CD3OD) δ8.32(d,J=2.0Hz,2H),7.94(s,2H),7.73(d,J=5.8Hz, 4H),7.39(t,J=6.7Hz,2H),7.18–7.10(m,4H),4.38(d,J=5.6Hz,2H),4.31(d ,J=5.6Hz,2H),2.74(d,J=3.7Hz,10H),2.34(s,6H),1.69(p,J=7.3Hz,4H), 1.31(dt,J=21.7,5.7Hz,20H),0.90–0.84(m,6H).HRMS(ESI-)m / z:[M-2K+H] - Calculated value C 54 H 65 O 10 S2 - 937.4024, measured value 937.4091.

[0587] Synthesis of compounds of formula (R)-5n

[0588]

[0589] By using preferred coupling reaction conditions, a white solid compound of formula (R)-5n (84% yield) was obtained from the halogenated product of formula (R)-4f and the arylboronic ester compound of formula 15h. f=0.63 (EA / MeOH = 4 / 1). 1 H NMR (400MHz, CD3OD) δ8.23(s,2H),8.07(s,2H),7.99(d,J=8.1Hz,2H),7.90–7.84(m,4H),7.56(t,J=7.7Hz,2H),7.45(t,J=7.2Hz,2H ),7.31(t,J=7.5Hz,2H),7.23(d,J=8.5Hz,2H),4.40(d,J=5.7Hz,2H),4.35(d,J=5.8Hz,2H),2.36(s,6H).HRMS(ESI-)m / z:[M-2K+H] - Calculated value C 36 H 29 O 10 S2 - 685.1207, measured value 685.1200.

[0590] Synthesis of compound (R)-5o

[0591]

[0592] By using preferred coupling reaction conditions, a white solid compound of formula (R)-5o (65% yield) was obtained from the halogenated product of formula (R)-4f and the arylboronic ester compound of formula 15i. f =0.33 (EA / MeOH = 4 / 1). 1 H NMR (500MHz, CD3OD) δ9.23(s,2H),8.29(s,2H),8.23(d,J=7.0Hz,2H),8.03(q,J=10.1,7.5Hz,8H),7.54(t,J=7.7Hz,2H),7. 47(t,J=7.3Hz,2H),7.33(t,J=7.6Hz,2H),7.27(d,J=8.4Hz,2H),4.46(d,J=5.6Hz,2H),4.41(d,J=5.6Hz,2H),2.34(s,6H). 13 C NMR (126MHz, CD3OD) δ152.5,142.2,139.2,136.8,135.2,134.8,132.6,132.5,132.2,130.7,129.5,1 29.3,128.9,127.9,127.9,127.5,127.5,127.1,126.4,125.6,99.6,56.4.HRMS(ESI-)m / z:[M-2K+H] - Calculated value C 40 H 25O8S2 - 823.1079, measured value 823.1080.

[0593] (4.2) Step 2:

[0594] Preferably, the acidification conditions are as follows: the coupling product (R)-5m-o (1.0 equivalent) obtained in step 1 is dissolved in methanol (0.01 mol / L), followed by the addition of concentrated hydrochloric acid (10.0 equivalent). The resulting mixture is stirred at 60°C for 5 hours. After the reaction is complete, the temperature is lowered to room temperature, and the solvent is removed by rotary evaporation under reduced pressure. The resulting solid is then dissolved in methanol, and the methanol solution is passed through a cation exchange resin Amberlyst 15, eluted twice with methanol, and the methanol is removed by rotary evaporation under reduced pressure. The resulting solid is then dried under vacuum at 50°C for 6 hours to obtain the final product, binaphthalene chiral dihydroxy disulfonic acid (R)-2d-f.

[0595] Synthesis of compound (R)-2d

[0596]

[0597] By using preferred acidification conditions, a brown solid compound (R)-2d (99% yield) was obtained from the coupling product (R)-5m. 1 H NMR (400MHz, CD3OD) δ8.34(s,2H),7.89(s,2H),7.74(dd,J=7.8,1.7Hz,2H),7.66(d,J=1.6Hz,2H),7.34(d,J=7.9Hz,2H),7.09(dd ,J=8.7,1.7Hz,2H),6.99(d,J=8.6Hz,2H),2.71(d,J=6.6Hz,10H),1.71–1.63(m,4H),1.31(d,J=20.2Hz,20H),0.95–0.82(m,6H). 13 C NMR (101MHz, CD3OD) δ150.0,137.8,136.3,134.9,132.2,131.3,131.0,130.8,129.5,128.1,127.6,126. 3,124.2,116.6,115.1,113.9,35.4,31.6,31.2,29.2,29.0,29.0,22.3,19.0,13.0.HRMS(ESI-)m / z:[MH] - Calculated value C 50 H 57 O8S2 - 849.3500, measured value 849.3476.

[0598] Synthesis of compounds of formula (R)-2e

[0599]

[0600] By using preferred acidification conditions, the brown solid compound (R)-2e was obtained from the coupling product (R)-5n (99% yield). 1 H NMR (500MHz, CD3OD) δ8.23(s,2H),8.00(s,2H),7.92(d,J=8.1Hz,2H),7.88(d,J=7.8Hz,2H),7.83(d,J =7.8Hz,2H),7.51(t,J=7.8Hz,2H),7.31(t,J=7.1Hz,2H),7.24(t,J=7.6Hz,2H),7.07(d,J=8.4Hz,2H). 13 C NMR (126MHz, CD3OD) δ151.1,139.2,134.0,131.6,130.9,130.4,129.3,128.0,127.5,126.9,126.2,124.2,124.1,123.1,114.7.HRMS(ESI-)m / z:[MH] - Calculated value C 32 H 21 O8S2 - 597.0683, measured value 597.0675.

[0601] Synthesis of compound (R)-2f

[0602]

[0603] By using preferred acidification conditions, a reddish-gray solid compound of formula (R)-2f (99% yield) was obtained from the coupling product of formula (R)-5o. 1 H NMR(500MHz,CD3OD)δ9.18(s,2H),8.21(d,J=9.8Hz,4H),8.03(t,J=9.8Hz,4H),7.96(d,J=8.2Hz ,4H),7.51(t,J=7.1Hz,2H),7.33(t,J=7.3Hz,2H),7.25(t,J=7.4Hz,2H),7.14(d,J=8.4Hz,2H). 13C NMR (126MHz, CD3OD) δ152.4,139.1,135.3,134.5,133.0,132.3,132.2,132.2,130.6,130.2, 129.8,129.2,128.3,127.6,127.3,126.8,125.4,125.1,124.3,116.0.HRMS(ESI-)m / z:[MH] - Calculated value C 40 H 25 O8S2 - 697.0996, measured value 697.0997.

[0604] Example 5

[0605] This embodiment describes the preparation method of compound (R)-2g, and the steps are as follows:

[0606]

[0607] Under nitrogen protection, compound (R)-2e (300.0 mg, 0.5 mmol) and 2 mL of pyridine were added sequentially to a three-necked flask equipped with a reflux condenser. Phosphorus oxychloride (307.0 mg, 2.0 mmol) was then slowly added. The resulting mixture was heated to 95 °C and stirred for 16 hours. After cooling to room temperature, 2 mL of water was added, and the mixture was heated to 100 °C and stirred for 4 hours. After cooling to room temperature again, pyridine was removed as much as possible by rotary evaporation under reduced pressure. 2 mL of concentrated hydrochloric acid was slowly added, during which solids precipitated. After the addition was complete, stirring was continued for 5 minutes. Subsequently, water in the system was removed as much as possible by rotary evaporation under reduced pressure. The residue was then placed at -20 °C until a large amount of insoluble matter precipitated, yielding a brown solid compound (R)-2 g (105.0 mg, 34% yield). 1 H NMR(500MHz,CD3OD)δ8.21(s,2H),8.16(s,2H),8.10(d,J=8.3Hz,2H),7.93(d,J=7.8Hz,2H) ,7.88(d,J=7.8Hz,2H),7.55(t,J=7.7Hz,4H),7.36(t,J=7.5Hz,2H),7.30(d,J=8.6Hz,2H). 13 C NMR (126MHz, CD3OD) δ145.0,137.4,133.1,132.0,131.7,131.6,131.3,128.5,127.9,127.3,127.0,126.7,126.3,125.9,124.9,122.6. 31P NMR(202MHz,CD3OD)δ1.7.HRMS(ESI-)m / z:[MH] - Calculated value C 32 H 20 O 10 PS2 - 659.0240, measured value 659.0236.

[0608] Example 1

[0609]

[0610] The procedure was as follows: Under nitrogen protection, titanium isooctanol Ti(EHO)4 (5.7 mg, 0.01 mmol) was added to a cyclohexane solution of compound (R)-1a (5.1 mg, 0.005 mmol). The mixture was heated to 60 °C and stirred for 30 minutes. After cooling to room temperature, 0.22 μL of water was added, and the mixture was heated to 75 °C and stirred for 8 hours. After cooling to room temperature, 2-allylphenol A (13.4 mg, 0.1 mmol) was added, and the mixture was heated to 75 °C and stirred for 24 hours. After the reaction was complete, the product compound B was obtained by direct purification by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 50:1). The ee value of the product was determined by supercritical fluid chromatography (SFC) (chiral column Daciel Chiralcel, OJ-H, isopropanol: carbon dioxide = 1:99, nozzle pressure = 200 bar CO2, flow rate = 3.0 mL / min, detection wavelength = 230 nm). Product: Colorless liquid, 99% yield, 97% ee. 1 H NMR(500MHz, CDCl3)δ7.15(d,J=7.3Hz,1H),7.10(t,J=7.7Hz,1H),6.86–6.79(m,1H),6.76(d,J=8.0Hz,1H),4.9 2(ddq,J=8.9,7.7,6.2Hz,1H),3.31(dd,J=15.4,8.8Hz,1H),2.82(dd,J=15.3,7.7Hz,1H),1.47(d,J=6.2Hz,3H). 13 C NMR (126MHz, CDCl3) δ159.6,128.1,127.2,125.1,120.3,109.5,79.6,37.3,21.9.[α] D 20.2 = +16.7 (c = 0.12, CHCl3).

[0611] Following the method described above, compound A was reacted with catalysts prepared using different chiral ligands, and the results are shown in Table 1 below:

[0612] Table 1

[0613]

[0614]

[0615]

[0616] Note: In Table 1, "-" indicates a yield of less than 1%, meaning almost no reaction.

[0617] Under the above conditions, when compounds 1i, 1l, and 1m were used as catalysts, compound B was almost impossible to obtain. The inventors found that by increasing the reaction temperature and reducing the amount of titanium isooctanol, compounds 1i, 1l, or 1m could also catalyze the reaction. Specific reaction results are shown in Table 2, and the specific experimental steps are as follows:

[0618] Titanium isooctanol Ti(EHO)4 (2.85 mg, 0.005 mmol) was added to a toluene solution of compound (R)-1 or (R)-2 (0.005 mmol). The mixture was heated to 60 °C and stirred for 30 min. After cooling to room temperature, 2-allylphenol A (13.4 mg, 0.1 mmol) was added, and the mixture was heated to 90 °C and stirred for 24 h. After the reaction was complete, the product compound B was obtained by direct purification by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 50:1). The ee value of the product was determined by supercritical fluid chromatography (SFC).

[0619]

[0620] Table 2

[0621]

[0622]

[0623] Example 2

[0624] Following the test method described in Example 1, this invention also catalyzed the cyclization reactions of other similar compound A, yielding a series of products similar to compound B, as shown in Table 3 below. The test results indicate that the compounds prepared by the method described in this invention possess excellent catalytic activity.

[0625] Table 3

[0626]

[0627]

[0628] Notes: In Tables 1, 2 and 3, the yield is: >= 70% (high), 30% (inclusive) to 70% (medium), and <30% (low); the ee value is: >= 85% (A), 60% (inclusive) to 85% (B), 15% (inclusive) to 60% (C), and <15% (D).

[0629] It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the invention. Furthermore, it should be understood that after reading the technical description of this invention, those skilled in the art can make various alterations, modifications, and / or variations to the invention, and all such equivalent forms also fall within the scope of protection defined by the appended claims.

Claims

1. A compound as shown in Formula I-1; ； in, A1 is phenyl, naphthyl, or absent; A1' is phenyl or naphthyl; R 1 H and C independently 1-16 Alkyl or adamantyl; R 2 and R 2 'Independently hydroxyl or -NR 2a R 2b ; R 2a and R 2b Independently for C 1-6 alkyl; R 3 and R 3 'Independently for H, C 1-6 Alkyl or -S(O)2NR 3a R 3b ; R 3a and R 3b Independently for C 1-6 alkyl; R 4 It is -S(O)2OH or a hydroxyl group, or two R groups. 4 Together When R 4 When it is a hydroxyl group, the R... 2 and R 2 ' is a hydroxyl group.

2. The compound of formula I-1 as described in claim 1, characterized in that, The compound shown in Formula I-1 satisfies any one of the following conditions: (1) When R 1 Independently for C 1-16 When alkyl, the C 1-16 Alkyl groups are straight-chain C466. 1-16 alkyl or branched C 1-16 alkyl; (2) When R 2a and R 2b Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl; (3) When R 3 and R 3 'Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, or n-pentyl; (4) When R 3a and R 3b Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl; (5) The general formula of the compound shown in Formula I-1 is: and / or .

3. The compound as shown in Formula I-1 as claimed in claim 2, characterized in that, The compound shown in Formula I-1 satisfies any one of the following conditions: (1) When R 1 Independently for C 1-16 When alkyl, the C 1-16 Alkyl groups are straight-chain C 1-16 alkyl; (2) When R 2a and R 2b Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl; (3) When R 3 and R 3 'Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl or n-pentyl; (4) When R 3a and R 3b Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl; (5) The general formula of the compound shown in formula I-1 is shown as I-1a, I-1b, I-1c or I-1d: 。 4. The compound of formula I-1 as described in claim 2 or 3, characterized in that, The compound shown in Formula I-1 satisfies any one of the following conditions: (1) When A1 and A1' are independently phenyl, the R 3 Or R 3 'The para or meta position of the phenyl group at the phenyl ring connection site described above;' (2) When A1 and A1' are independently phenyl, the aforementioned or The meta position located at the phenyl-naphthalene ring connection site on the phenyl group; (3) When the R mentioned above 1 Independently for linear C 1-16 When alkyl, the straight-chain C 1-16 Alkyl n-hexadecyl or n-octyl.

5. The compound of formula I-1 as described in claim 4, characterized in that, The compound shown in Formula I-1 satisfies any one of the following conditions: (1) When A1 and A1' are independently naphthyl groups, the aforementioned or Located at position 8 of the naphthyl group; (2) When the R mentioned above 1 Independent for branch C 1-16 When alkyl, the C of the branched chain 1-16 Alkyl groups are branched C 3-6 alkyl.

6. The compound of formula I-1 as described in claim 5, characterized in that, When the R 1 Independent for branch C 1-16 When alkyl, the C of the branched chain 1-16 The alkyl group is tert-butyl.

7. The compound of formula I-1 as claimed in claim 1, characterized in that, The compound shown in Formula I-1 satisfies any one of the following conditions: (1) A1 is phenyl or naphthyl; (2) R 1 Independently for C 1-16 Alkyl or adamantyl; (3) R 2 and R 2 'for -NR 2a R 2b ; (4) R 3 and R 3 'Independently for C 1-6 Alkyl or -S(O)2NR 3a R 3b ; (5) R 4 It is -S(O)2OH; (6) and Independently , , , , or ; (7) for , , , , , , or .

8. The compound of formula I-1 as described in claim 7, characterized in that, for , , , , , or .

9. The compound of formula I-1 as claimed in claim 1, characterized in that, It is any of the following schemes: Option 1: In the compound shown in Formula I-1: A1 is phenyl or naphthyl; When A1' is naphthyl, the R 1 C 1-16 Alkyl or adamantyl; the R 2 'for -NR 2a R 2b ; When R 4 When it is a hydroxyl group, the R... 3 and R 3 'For H; Option 2: In the compound shown in Formula I-1: A1 is phenyl or naphthyl; R 1 For H or C 1-16 alkyl; R 3 For H or C 1-6 alkyl; R 4 It is -S(O)2OH or hydroxyl group; When R 2 and R 2 Independently for -NR 2a R 2b At that time, the R mentioned 1 C 1-16 alkyl; When R 2 and R 2 When it is independently a hydroxyl group, the R... 1 For H; When R 2 and R 2 'Independently a hydroxyl group, R 4 When it is -S(O)2OH, Al and Al' are independently naphthyl groups; Option 3: In the compound shown in Formula I-1: A1 is a phenyl group; R 1 C 1-16 Alkyl or adamantyl; R 2 and R 2 'for -NR 2a R 2b ; R 3 and R 3 'For C 1-6 alkyl; R 4 It is -S(O)2OH.

10. The compound of formula I-1 as claimed in claim 1, characterized in that, The compound represented by Formula I-1 is any of the following compounds and / or its isomers: 。 11. A method for preparing a compound of formula I-1 as described in any one of claims 1-10, characterized in that, The preparation method is one of the following methods 1, 2, 3 or 4: Method 1: When R 4 When the form is -S(O)2OH, the preparation method of the compound shown in Formula I-1 includes the following steps: under acidic reagent, compound II-a is subjected to an acidification reaction in a solvent as shown in the following formula to obtain the compound shown in Formula I-1; ； Where Z and Z' are independently hydroxyl groups or -SO3M 1a ; M 1a Independently Na or K; R 13 and R 13‘ Independently -ONa, -OK, or -NR 2a R 2b ;R 2a and R 2b The definitions are as described in any one of claims 1-10; Method 2: When R 4 When OH, the preparation method of the compound shown in Formula I-1 includes the following steps: in the presence of an acidic reagent or BBr3, compound II-b is subjected to a deprotection reaction in a solvent as shown in the following formula to obtain the compound shown in Formula I-1; ； Among them, R 15 and R 15’ Independently a hydroxyl protecting group or C 1-3 Alkyl; M 2a and M 2b Independently Na or K; Method 3: When two R 4 Together The method for preparing the compound as shown in Formula I-1 includes the following steps: Step (1): The compound I-1 obtained in method 2 and phosphorus oxychloride are subjected to esterification reaction in a solvent to obtain a mixed solution; Step (2): The mixed solution obtained in step (1) is subjected to a hydrolysis reaction in water to obtain the compound of formula I-1; ； Method 4: When R 4 When the form is -S(O)2OH, the preparation method of the compound shown in Formula I-1 includes the following steps: in the presence of an oxidant and formic acid, compound II-d is oxidized in a solvent according to the following formula to obtain the compound shown in Formula I-1; ； Among them, R 16a and R 16b Independently for C 1-3 alkyl; R 18 For R 3 R 18a -S(O2)R 2 ; R 19 -S(O2)R 2’ R 19a For R 3’ ; In methods 1-4, R 2 R 2’ R 3 and R 3’ The definitions are as described in any one of claims 1-10.

12. A catalyst composition, characterized in that, It includes the compound as shown in Formula I-1 as claimed in any one of claims 1-10 and the titanium salt.

13. The catalyst composition according to claim 12, characterized in that, The titanium salt is one or more of titanium tetramethanol, titanium tetraisopropoxide, titanium tetratert-butoxide, titanium tetraisobutoxide, titanium tetrachloride, titanium triisopropoxide chloride, and titanium isooctyl alcohol.

14. The catalyst composition according to claim 13, characterized in that, The titanium salt is titanium isooctyl alcohol.

15. The use of a compound of formula I-1 as described in any one of claims 1-10 or a catalyst composition as described in any one of claims 12-14 as a catalyst in the preparation of compound B; The preparation method of compound B includes the following steps: In the presence of the compound shown in Formula I-1 and the titanium salt, compound A is subjected to a cyclization reaction in a solvent as follows to obtain compound B; ； ； Among them, R 8 R 9 R 10 and R 11 Independent of H, halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, cyano, -C(=O)OR 8-1 C 3-6 cycloalkyl, C 6-18 Aryl or R 8-2 Replacement C 6-18 Aryl; R 8-1 C 1-6 alkyl; R 8-2 C 2-6 alkenyl or hydroxyl groups; Or, R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 3-6 cycloalkyl, C 6-18 aryl or ; R 12 and R 13 H and C independently 1-6 Alkyl or C 6-18 Aryl, or R 12 and R 13 Together with the carbon atom it is attached to, they form C 3-6 cycloalkyl; n is 1, 2, or 3.

16. The application as described in claim 15, characterized in that, The application satisfies any one of the following conditions: (1) When R 8 R 9 R 10 and R 11 Independently for C 1-6 Alkyl or -OC 1-6 When alkyl, the C 1-6 Alkyl or -OC 1-6 C in alkyl 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl; (2) When R 8 R 9 R 10 and R 11 Independently for C 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; (3) When R 8 R 9 R 10 and R 11 Independently for C 6-18 Aryl or R 8-1 Replacement C 6-18 When aryl, the C 6-18 aryl or the R 8-1 Replacement C 6-18 C in aryl 6-18 The aryl group is phenyl, naphthyl, phenanthryl, or anthracene; (4) When R 8-1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl; (5) When R 8-2 C 2-6 When alkenyl, the C 2-6 The alkenyl group is vinyl or propenyl; (6) When R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; (7) When R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 6-18 When aryl, the C 6-18 The aryl group is phenyl, naphthyl, phenanthryl, or anthracene; (8) When R 12 and R 13 Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, or isopropyl; (9) When R 12 and R 13 Independently for C 6-18 When aryl, the C 6-18 The aryl group is phenyl, naphthyl, phenanthryl, or anthracene; (10) The compound A is , , , , , , , , , , , , , , , , , , , or ; (11) When the compound shown in Formula I-1 is When; the compound B is .

17. The application as described in claim 16, characterized in that, The application satisfies any one of the following conditions: (1) When R 8 R 9 R 10 and R 11 Independently for C 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclohexyl; (2) When R 8 R 9 R 10 and R 11 Independently for C 6-18 Aryl or R 8-1 Replacement C 6-18 When aryl, the C 6-18 aryl or the R 8-1 Replacement C 6-18 C in aryl 6-18 The aryl group is phenyl; (3) When R 8-1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl; (4) When R 8-2 C 2-6 When alkenyl, the C 2-6 alkenyl is ; (5) When R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 3-6 When cycloalkyl, the C 3-6 The cycloalkyl group is cyclohexyl; (6) When R 8 R 9 R 10 and R 11 Any two adjacent substituents together with the carbon atom they are attached to form a C12 carbon atom. 6-18 When aryl, the C 6-18 The aryl group is phenyl; (7) When R 12 and R 13 Independently for C 1-6 When alkyl, the C 1-6 The alkyl group is methyl; (8) When R 12 and R 13 Independently for C 6-18 When aryl, the C 6-18 The aryl group is phenyl; (9) When the compound shown in Formula I-1 is When; the compound B is .

18. A compound II-a, compound II-b, compound II-d, or compound IV-d: ； in, Z and Z' are independently hydroxyl groups or -SO3M 1a M 1a Independently Na or K; R 13 and R 13‘ Independently -ONa, -OK, or -NR 2a R 2b ; R 15 and R 15’ Independently a hydroxyl protecting group or C 1-3 alkyl; M 2a and M 2b Independently Na or K; R 16a and R 16b Independently for C 1-3 alkyl; R 18 For R 3 ;R 18a -S(O2)R 2 ; R 19 -S(O2)R 2’ ;R 19a For R 3’ ; R 1 R 3 R 3’ R 2a R 2b The definitions of A1 and A1' are as described in any one of claims 1-10.

19. The compound II-a, compound II-b, compound II-d, or compound IV-d as claimed in claim 18; characterized in that, Compound II-a, compound II-b, compound II-d, or compound IV-d have the following general formula: 。 20. A compound II-a, compound II-b, compound II-d, compound III-d, or compound IV-d as described in claim 18 or 19, characterized in that, Compound II-a, compound II-b, compound II-d, compound III-d, or compound IV-d are any of the following compounds and / or their isomers: 。

Images