Synthesis method of sulfur-containing benzodihydrofuran structure and benzofuran structure carbon glycoside compound

Abstract

The invention discloses a sulfur-containing benzodihydrofuran structure C-glycoside compound and a synthesis method of the benzofuran structure C-glycoside compound, and the method comprises the following steps: by taking a compound as shown in a formula (3) and sulfur-containing sugar alkene as shown in a formula (2) as reaction raw materials, reacting under the action of an activating reagent and alkali to obtain the sulfur-containing benzodihydrofuran structure C-glycoside compound. And reacting to obtain the sulfur-containing benzodihydrofuran structure carbon glycoside compound. Or sulfur-containing sugar alkene C-glycoside as shown in a formula (4) is taken as a reaction raw material and reacts in an organic solvent under the action of an oxidizing agent and alkali to obtain the benzofuran structure C-glycoside compound. The method has the advantages of mild reaction conditions, cheap and easily available raw materials, simple reaction operation and high yield; reaction substrates are easy to prepare; the reaction provided by the invention can be used for constructing novel sulfur-containing benzodihydrofuran structure and benzofuran structure carbon glycoside compounds.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound process application, and in particular relates to a method for synthesizing sulfur-containing benzodihydrofuran structure and benzofuran structure carbonyl glycoside compounds. Background Art

[0002] Sulfur-containing benzodihydrofuran and benzofuran carbon glycoside compounds are widely present in natural products and drugs. Therefore, the synthesis methods of sulfur-containing benzodihydrofuran and benzofuran carbon glycoside compounds have always attracted wide attention. Nowadays, scientists have designed a variety of glycosylation methods, but the existing preparation methods have a common disadvantage, that is, the raw materials of the compounds need to be pre-functionalized, and the synthesis is carried out through multiple steps of transition metal catalysis. The synthesis route is long and time-consuming and reagent-intensive.

[0003] Therefore, it is particularly important to find a universal, efficient, environmentally friendly, mild and economical method for synthesizing sulfur-containing benzodihydrofuran and benzofuran carbonyl glycosides. Summary of the invention

[0004] The present invention overcomes the limitations of the traditional synthesis of sulfur-containing aryl carbon glycoside compounds, uses the Pummerer reaction strategy, the reaction is highly efficient, does not require pre-functionalization of the reaction substrate, does not require the participation of transition metals, and directly uses simple and readily available raw materials to obtain different sulfur-containing benzodihydrofuran structure carbon glycoside compounds and benzofuran structure carbon glycoside compounds. In view of this, the present invention designs a reaction method for preparing a sulfur-containing benzodihydrofuran structure carbon glycoside compound by reacting a sulfur-containing sugar ene with another molecule of a phenol compound under the action of an activating reagent and a base. At the same time, a reaction method for preparing a benzofuran structure carbon glycoside compound by reacting a sulfur-containing sugar ene with another molecule of a phenol compound under the action of an oxidant and a base is also invented and designed.

[0005] The present invention provides a sulfur-containing benzodihydrofuran structure carbonyl glycoside compound, the structural formula of which is shown in formula (1):

[0006]

[0007] in,

[0008] R is selected from hydrogen, alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from halogen-substituted phenyl; the substituted benzyl is selected from alkoxy-substituted benzyl and benzothiophene benzyl;

[0009] Preferably,

[0010] R is selected from hydrogen, C1-C15 alkyl, halogen, ester group, aldehyde group, aryl group, substituted aryl group, polysubstituted alkyl halogen group, cycloalkyl group, substituted benzyl group, 2-methylenethiophene; wherein the substituted aryl group is selected from 4-bromophenyl group; the substituted benzyl group is selected from 4-methoxybenzyl group, 4-ethoxybenzyl group, 2-benzothiophene benzyl group;

[0011] More preferably,

[0012] R is selected from hydrogen, o-methyl, o-tert-butyl, o-chloro, o-fluoro, p-methyl, p-ethyl, bromo, fluoro, methyl formate, formaldehyde, gem-dimethylphenyl, phenyl, bromo substituted phenyl, 2,3-dimethyl, 2-methyl-3-fluoro, 2-methyl-3-chloro, 3-chloro-4-methyl, 3-fluoro-4-methyl, 2,3-cyclobutyl, 4-methoxybenzyl, 4-ethoxybenzyl, 2-methylenethiophene.

[0013] Furthermore, the sulfur-containing benzodihydrofuran structure carbon glycoside compounds represented by formula (1) of the present invention include:

[0014]

[0015]

[0016]

[0017]

[0018] The present invention also proposes a benzofuran structure carbon glycoside compound, the structural formula of which is shown in formula (5):

[0019]

[0020] in,

[0021] R is selected from hydrogen, alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from halogen-substituted phenyl; the substituted benzyl is selected from alkoxy-substituted benzyl and benzothiophene benzyl;

[0022] Preferably,

[0023] R is selected from hydrogen, C1-C15 alkyl, halogen, ester group, aldehyde group, aryl group, substituted aryl group, polysubstituted alkyl halogen group, cycloalkyl group, substituted benzyl group, 2-methylenethiophene; wherein the substituted aryl group is selected from 4-bromophenyl group; the substituted benzyl group is selected from 4-methoxybenzyl group, 4-ethoxybenzyl group, 2-benzothiophene benzyl group;

[0024] More preferably,

[0025] R is selected from hydrogen, o-methyl, o-tert-butyl, o-chloro, o-fluoro, p-methyl, p-ethyl, bromo, fluoro, methyl formate, formaldehyde, gem-dimethylphenyl, phenyl, bromo substituted phenyl, 2,3-dimethyl, 2-methyl-3-fluoro, 2-methyl-3-chloro, 3-chloro-4-methyl, 3-fluoro-4-methyl, 2,3-cyclobutyl, 4-methoxybenzyl, 4-ethoxybenzyl, 2-methylenethiophene.

[0026] Furthermore, the benzofuran structure carbon glycoside compound represented by formula (5) of the present invention includes:

[0027]

[0028] The present invention also provides a method for synthesizing a sulfur-containing benzodihydrofuran structure carbon glycoside compound, wherein the sulfur-containing glycoside compound shown in formula (2) and the phenol compound shown in formula (3) are used as reaction raw materials, and under the action of an activation reagent and a base, in an organic solvent, a reaction is performed to obtain a sulfur-containing benzodihydrofuran structure carbon glycoside compound shown in formula (1), and the reaction process is shown in reaction formula (a);

[0029]

[0030] in,

[0031] R is selected from hydrogen, alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from halogen-substituted phenyl; the substituted benzyl is selected from alkoxy-substituted benzyl and benzothiophene benzyl;

[0032] Preferably,

[0033] R is selected from hydrogen, C1-C15 alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted C1-C15 alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from 4-bromophenyl; the substituted benzyl is selected from 4-methoxybenzyl, 4-ethoxybenzyl, 2-benzothiophene benzyl;

[0034] More preferably,

[0035] R is selected from hydrogen, o-methyl, o-tert-butyl, o-chloro, o-fluoro, p-methyl, p-ethyl, bromo, fluoro, methyl formate, formaldehyde, gem-dimethylphenyl, phenyl, bromophenyl, 2,3-dimethyl, 2-methyl-3-fluoro, 2-methyl-3-chloro, 3-chloro-4-methyl, 3-fluoro-4-methyl, 2,3-cyclobutyl, 4-methoxybenzyl, 4-ethoxybenzyl, 2-methylenethiophene.

[0036] In the present invention, in reaction formula (a), the molar ratio of the sulfur-containing sugar ene represented by formula (2) to the phenol compound represented by formula (3) is 1:(1-2); preferably, it is 1:1.5.

[0037] In the present invention, in reaction formula (a), the activating agent is selected from one or more of trifluoroacetic anhydride, acetic anhydride, trifluoromethanesulfonic anhydride, trimethylchlorosilane, trifluoromethanesulfonic anhydride trimethylsilicone, perfluoropropionic anhydride, perfluorobutyric anhydride, etc.; preferably, it is trifluoroacetic anhydride.

[0038] In the present invention, in reaction formula (a), the base is selected from one or more of potassium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, pyridine, 2,6-lutidine, 2,4,6-trimethylpyridine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; preferably, it is 2,6-lutidine.

[0039] In the present invention, in reaction formula (a), the organic solvent is selected from one or more of dichloromethane, tetrahydrofuran, nitromethane, toluene, chloroform, acetone, etc.; preferably, dichloromethane and tetrahydrofuran.

[0040] In the present invention, in reaction formula (a), the molar ratio of the activation reagent to the sulfur-containing sugar ene is (1.5-10):1; preferably, it is 3:1.

[0041] In the present invention, in reaction formula (a), the molar ratio of the base to the sulfur-containing sugar ene is (1.5-10):1; preferably, it is 3:1.

[0042] In the present invention, in reaction formula (a), the reaction temperature is -10 to 60°C; preferably, 0°C and 60°C.

[0043] In the present invention, in reaction formula (a), the reaction time is 8-24 hours; preferably, it is 24 hours.

[0044] In the present invention, in reaction formula (a), the reaction is carried out in an air atmosphere.

[0045] The present invention also proposes a method for synthesizing a benzofuran structure carbon glycoside compound, wherein the sulfur-containing glycoside shown in formula (4) is used as a reaction raw material, and under the action of an oxidant and a base, in an organic solvent, a benzofuran structure carbon glycoside compound as shown in formula (5) is obtained by reaction, and the reaction process is shown in reaction formula (b):

[0046]

[0047] in,

[0048] R is selected from hydrogen, alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from halogen-substituted phenyl; the substituted benzyl is selected from alkoxy-substituted benzyl and benzothiophene benzyl;

[0049] Preferably,

[0050] R is selected from hydrogen, C1-C15 alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted C1-C15 alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from 4-bromophenyl; the substituted benzyl is selected from 4-methoxybenzyl, 4-ethoxybenzyl, 2-benzothiophene benzyl;

[0051] More preferably,

[0052] R is selected from hydrogen, o-methyl, o-tert-butyl, o-chloro, o-fluoro, p-methyl, p-ethyl, bromo, fluoro, methyl formate, formaldehyde, gem-dimethylphenyl, phenyl, bromophenyl, 2,3-dimethyl, 2-methyl-3-fluoro, 2-methyl-3-chloro, 3-chloro-4-methyl, 3-fluoro-4-methyl, 2,3-cyclobutyl, 4-methoxybenzyl, 4-ethoxybenzyl, 2-methylenethiophene.

[0053] In the present invention, in reaction formula (b), the oxidant is selected from one or more of hydrogen peroxide, oxygen, 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), meta-chloroperbenzoic acid (m-CPBA), etc.; preferably, it is meta-chloroperbenzoic acid (m-CPBA).

[0054] In the present invention, in reaction formula (b), the base is selected from one or more of potassium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, pyridine, 2,6-lutidine, 2,4,6-trimethylpyridine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; preferably, it is potassium hydroxide.

[0055] In the present invention, in reaction formula (b), the molar ratio of the oxidant to the sulfur-containing glycoside is (1.5-10):1; preferably, it is 2.2:1.

[0056] In the present invention, in reaction formula (b), the molar ratio of the base to the sulfur-containing glycoside is (1.5-10):1; preferably, it is 2:1.

[0057] In the present invention, in reaction formula (b), the organic solvent is selected from one or more of dichloromethane, tetrahydrofuran, nitromethane, toluene, chloroform, acetone, etc.; preferably, dichloromethane and tetrahydrofuran.

[0058] In the present invention, in reaction formula (b), the reaction temperature is -10 to 60°C; preferably, 0°C and 60°C.

[0059] In the present invention, in reaction formula (b), the reaction time is 8-24 hours; preferably, 24 hours.

[0060] In the present invention, in reaction formula (b), the reaction is carried out in an air atmosphere.

[0061] In a specific embodiment, the synthesis reaction of the present invention is carried out in a reaction bottle A, and sulfur-containing sugar olefin (2) (Ummol), phenol compound (3) (Vmmol), activation reagent (Wmmol), base (Xmol), and organic solvent (PmL) are added to the reaction bottle A, and the reaction system is stirred at 0°C in an air atmosphere for 24 hours; after the reaction is completed, the mixture is washed with a saturated sodium bicarbonate aqueous solution, extracted with an organic solvent, the organic solvent is dried, and then added with silica gel and dried, and separated by column chromatography to obtain the target product.

[0062] In another specific embodiment, the synthesis reaction of the present invention is carried out in a reaction bottle B, and sulfur-containing glycoside (4) (Ymmol), an oxidant (Zmmol), a base (Qmol), and an organic solvent (OmL) are added to the reaction bottle B, and the reaction system is stirred at 0-60°C in an air atmosphere for 24 hours; after the reaction is completed, the mixture is washed with a saturated sodium bicarbonate aqueous solution, extracted with an organic solvent, the organic solvent is dried, and then silica gel is added and dried, and the target product is obtained by column chromatography separation.

[0063] The present invention also provides a sulfur-containing benzodihydrofuran structure carbonyl glycoside compound as shown in formula (1) prepared according to the above-mentioned synthesis method of the present invention.

[0064] The present invention also provides a benzofuran structure carbonyl glycoside compound as shown in formula (5) prepared according to the above-mentioned synthesis method of the present invention.

[0065] The present invention also proposes that the sulfur-containing benzodihydrofuran structure carbon glycoside compound shown in formula (1) or the benzofuran structure carbon glycoside compound shown in formula (5) can be used as or in the preparation of dapagliflozin and ipragliflozin small molecule drug analogs.

[0066] The yield of the sulfur-containing benzodihydrofuran shown in formula (1) and the benzofuran structure carbon glycoside compound shown in formula (5) prepared by the synthesis method of the present invention is 55% or more.

[0067] The invention has the following advantages: raw materials do not need to be pre-functionalized, do not need excessive metal catalysis, raw materials are cheap and easy to obtain, reaction substrates are easy to prepare, reaction operation is simple, reaction is efficient, yield is high, sulfur-containing sugar ene is simple to prepare, stable, and has no irritating odor; reaction conditions are relatively mild. The sulfur-containing sugar ene of the invention reacts with a phenol compound to obtain a sulfur-containing benzodihydrofuran structure carbon glycoside compound, the reaction operation is simple, the reaction conditions are relatively mild, and the compound can be used to construct a novel sulfur-containing benzodihydrofuran structure carbon glycoside compound, which is suitable for large-scale industrial production. DETAILED DESCRIPTION

[0068] The present invention is further described in detail in conjunction with the following specific examples, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, the changes and advantages that can be thought of by those skilled in the art are included in the present invention, and the attached claims are the scope of protection. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are all common knowledge and common common sense in the art, and the present invention has no special restrictions. The data given in the following examples include specific operations and reaction conditions and products. The purity of the product is identified by nuclear magnetic resonance.

[0069] The synthesis reaction of sulfur-containing benzodihydrofuran and benzofuran structure carbon glycoside compounds of the present invention comprises the following steps:

[0070] As shown in reaction formula (a), the synthesis reaction of the present invention is to add sulfur-containing sugar olefin (2), phenol compound (3), activation reagent, base, organic solvent into reaction bottle A, and stir the reaction system at 0°C in air atmosphere for 24 hours; after the reaction is completed, wash with saturated sodium bicarbonate aqueous solution, extract with organic solvent, dry the organic solvent, add silica gel and spin dry, and separate by column chromatography to obtain the target product.

[0071] As shown in reaction formula (b), the synthesis reaction of the present invention is to add sulfur-containing glycoside (4), oxidant, base, and organic solvent into reaction bottle B, and stir the reaction system at 0-60° C. in air atmosphere for 24 hours; after the reaction is completed, washing with saturated sodium bicarbonate aqueous solution, extraction with organic solvent, drying the organic solvent, adding silica gel and spin drying, and separation by column chromatography to obtain the target product.

[0072] The sulfur-containing benzodihydrofuran and benzofuran structure carbon glycoside compounds shown in Table 1 are all products synthesized by the method of the present invention, and there is no public document that discloses these compounds.

[0073] Table 1 New sulfur-containing benzodihydrofuran structure carbon glycoside compounds of the present invention

[0074]

[0075]

[0076]

[0077]

[0078]

[0079] Example 1

[0080] Synthesis of compounds 1a and 1b:

[0081]

[0082] 2 (63.2 mg, 0.1 mmol, 1 equiv), phenol (14.1 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and the mixture was washed with 10 mL of saturated sodium bicarbonate aqueous solution. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1a (20.5 mg, 29%). 1 H NMR (400 MHz, CDCl 3 )δ7.67(dd,J=7.5,1.1Hz,1H),7.50–7.44(m,2H),7.41–7.18(m,12H),7.11–7.05(m,2H),6.94(td,J=7.5,0 .7Hz,1H),6.85(d,J=8.0Hz,1H),5.83(s,1H),5.12(d,J=10.7Hz,1H),4.96(d,J=10.7Hz,1H),4.69(d,J=10 .9Hz,1H),4.47(dt,J=14.4,11.5Hz,3H),4.03(d,J=9.4Hz,1H),3.79(m,1H),3.57(m,2H),3.35(t,J=9.2Hz ,1H),2.36(dt,J=11.7,7.3Hz,1H),2.16(dt,J=11.7,7.4Hz,1H),1.41–1.08(m,22H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3)δ158.58,138.57,138.06,137.90,129.65,128.42,128.38,128.33,128.04,127.95, 127.90,127.84,127.76,127.70,127.58,126.26,121.98,110.28,83.88,75.88,74.81 ,73.50,69.97,61.03,31.94,29.64,29.57,29.45,29.36,29.34,29.10,28.97,29.04, . 22.71,14.14.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,840.HRMS(ESI)Calcd for C 45 H 56 O 5 SNa 731.3746,Found 731.3742.

[0083] Dosage 1b(41mg.58%). 1 H NMR (400MHz, CDCl 3 )δ7.44(dd,J7.8,1.4Hz,2H),7.38–7.17(m,13H),7.02(dd,J6.6,2.9Hz,2H),6.93(td, J7.5,0.8Hz,1H),6.89–6.85(m,1H),6.18(s,1H),4.77–4.67(m,2H),4.59(d,J12.1Hz,1 H), 4.44(dd,J25.1,11.9Hz,2H),4.18(t,J6.9Hz,2H),3.81(dd,J7.4,2.0Hz,1H),3.6 3–3.50(m,3H),2.23(m,1H),2.05–1.92(m,1H),1.45–1.09(m,20H),0.90(t,J6.9Hz,3H). 13 C NMR (101MHz, CDCl 3)δ159.34,138.20,137.78,137.76,129.65,128.40,128.29,128.24,127.14,127.83,127 .64,127.54,127.51,126.38,125.26,121.32,110.13,109.23,80.28,75.07,73.54,73.35 ,71.54,71.32,69.97,58.16,31.94,29.64,29.57,29.43,29.36,29.12,29.10,29.02,28. 29,22.70,14.13.IR(neat,cm-1)3052,2962,1527,1380,1136,1069,842.HRMS(ESI)Calcd for C 45 H 56 O 5 SNa 731.3746,Found 731.3743.

[0084] Example 2

[0085] Synthesis of compounds 1c and 1d:

[0086]

[0087] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-methylphenol (16.2 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and the mixture was washed with 10 mL of saturated sodium bicarbonate aqueous solution. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1c (20 mg, 27.7%). 1 H NMR (400 MHz, CDCl 3)δ 7.51–7.45 (m, 3H), 7.42–7.19 (m, 12H), 7.12–7.05 (m, 2H), 7.01 (dd, J = 8.1, 1.3 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 5.80 (s, 1H), 5.14 (d, J = 10.8 Hz, 1H), 4.96 (d, J = 10.8 Hz, 1H), 4.74–4.66 (m, 1H), 4.54–4.41 (m, 3H), 4.02 (d, J = 9.4 Hz, 1H), 3.78 (m, 1H), 3.59 (m, 2H), 3.37 (t, J = 9.1 Hz, 1H), 2.37 (dt, J = 11.7, 7.3 Hz, 1H), 2.29 (d, J = 5.1 Hz, 3H), 2.16 (dt, J = 11.7, 7.4 Hz, 1H), 1.43–1.10 (m, 20H), 0.88 (t, J = 6.9 Hz, 3H). 13 C NMR(101MHz,CDCl 3 )δ 156.55, 138.65, 138.08, 137.94, 128.42, 128.35, 128.30, 127.92, 127.91, 127.75, 127.63, 127.57, 126.07, 110.34, 109.77, 83.76, 75.75, 74.79, 73.49, 70.01, 61.15, 31.92, 29.63, 29.57, 29.45, 29.35, 29.28, 29.11, 28.97, 22.69, 21.10, 14.12. IR(neat, cm-1) 3052, 2962, 1528, 1380, 1132, 1069, 840. HRMS(ESI) Calcd for C 46 H 58 O 5 SNa 745.3903, Found 745.3901.

[0088] Colorless liquid 1d (40 mg, 55.3%). 1 H NMR(400MHz,CDCl 3)δ7.48–7.42(m,2H),7.40–7.21(m,12H),7.05–6.95(m,4H),6.74(d,J=8.7Hz,1H),6.15 (s,1H),4.74(d,J=2.0Hz,2H),4.61(d,J=12.1Hz,1H),4.47(d,J=12.1Hz,1H),4.38(d,J= 11.6Hz,1H),4.19(d,J=1.8Hz,1H),4.15(d,J=11.6Hz,1H),3.83–3.76(m,1H),3.63–3.49 (m,3H),2.32–2.18(m,4H),2.03–1.92(m,1H),1.45–1.08(m,20H),0.89(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ157.50,138.23,137.80,137.76,130.56,130.23,128.40,128.29,128.25,128.21,127.8 5,127.57,127.53,127.34,125.99,125.55,110.21,108.71,80.11,75.34,73.48,73.35,71 .39,71.15,70.02,58.25,31.93,29.64,29.58,29.43,29.36,29.16,29.12,29.02,28.29,2 2.70,20.88,14.12.IR(neat,cm-1)3053,2965,1528,1380,1136,1071,840.HRMS(ESI)Calcd for C 46 H 58 O 5 SNa 745.3903,Found 745.3898.

[0089] Example 3

[0090] Synthesis of compounds 1e and 1f:

[0091]

[0092] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-ethylphenol (18.3 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1e (20.1 mg, 27.3%). 1 H NMR (400 MHz, CDCl 3 )δ7.49(dd,J=12.4,4.3Hz,3H),7.41–7.20(m,12H),7.07(dd,J=6.6,2.9Hz,2H),7.03(dd,J=8.2,1.9Hz,1H), 6.75(d,J=8.2Hz,1H),5.81(s,1H),5.14(d,J=10.8Hz,1H),4.96(d,J=10.8Hz,1H),4.72–4.64(m,1H),4.47(d t,J=14.5,11.5Hz,3H),4.01(d,J=9.4Hz,1H),3.77(m,1H),3.57(m,2H),3.36(t,J=9.2Hz,1H),2.58(q,J=7.6 Hz,2H),2.36(dt,J=11.8,7.3Hz,1H),2.15(dt,J=11.8,7.4Hz,1H),1.40–1.06(m,20H),0.87(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ156.66,138.72,138.09,137.89,137.70,129.03,128.35,128.34,128.31,128.01,127.92,1 27.75,127.62,127.59,127.57,127.24,126.03,110.50,109.76,83.83,77.30,76.90,75.79,74 .76,73.50,70.05,61.18,31.93,29.64,29.58,29.46,29.36,29.34,29.16,29.10,28.97,28.4 0,22.70,15.70,14.13.IR(neat,cm-1)3058,2962,1526,1380,1137,1069,841.HRMS(ESI)Calcd for C47 H 60 O 5 SNa 759.4059,Found759.4046.

[0093] Colorless liquid 1f (40.2 mg, 54.7%). 1 H NMR (400 MHz, CDCl 3 )δ7.47–7.42(m,2H),7.39–7.21(m,11H),7.05–6.97(m,4H),6.76(d,J=8.0Hz,1H),6.15(s,1H),4 .77–4.67(m,2H),4.61(d,J=12.1Hz,1H),4.46(d,J=12.1Hz,1H),4.39(d,J=11.6Hz,1H),4.20(d, J=1.8Hz,1H),4.15(d,J=11.6Hz,1H),3.84–3.78(m,1H),3.62–3.52(m,3H),2.55(q,J=7.6Hz,2H) ,2.23(m,1H),2.02–1.91(m,1H),1.44–1.16(m,20H),1.13(t,J=7.6Hz,3H),0.89(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ157.60,138.23,137.81,137.78,137.25,129.07,128.40,128.28,128.23,128.15,127.91,127 .85,127.82,127.59,127.53,127.40,126.01,124.38,110.27,108.77,80.33,75.31,73.53,73.3 5,71.51,71.19,69.99,58.36,31.93,29.64,29.57,29.43,29.35,29.20,29.09,29.01,28.35,28 .31,22.70,15.89,14.12.IR(neat,cm-1)3048,2963,1528,1380,1136,1069,840.HRMS(ESI)Calcd forC 47 H 60 O 5 SNa 759.4059,Found 759.4051.

[0094] Example 4

[0095] Synthesis of compounds 1g and 1h:

[0096]

[0097] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-fluorophenol (16.8 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain 1 g (20.0 mg, 27.6%) of a colorless liquid. 1 HNMR (400MHz, CDCl 3 )δ7.48–7.43(m,2H),7.39(m,3H),7.36–7.22(m,9H),7.13–7.07(m,2H),6.91(td,J=8.8, 2.8Hz,1H),6.77(dd,J=8.7,4.1Hz,1H),5.81(s,1H),5.09(d,J=10.6Hz,1H),4.95(d,J=10 .6Hz,1H),4.71(d,J=10.9Hz,1H),4.54–4.43(m,3H),4.00(d,J=9.4Hz,1H),3.75(m,1H),3 .58(m,2H),3.37(t,J=9.2Hz,1H),2.26(m,2H),1.44–1.12(m,20H),0.88(t,J=6.9Hz,3H). 19 FNMR (376MHz, CDCl 3 )δ-121.52(td,J=8.6,4.1Hz). 13 CNMR (101MHz, CDCl 3)δ159.23, 156.86, 154.54, 138.25, 137.96, 137.79, 128.47, 128.40, 128.33, 127.93, 127.88, 127.84, 127.82, 127.62, 116.18, 115.94, 115.16, 114.90, 110.65, 110.54, 83.79, 75.54, 74.87, 73.51, 69.67, 61.25, 31.92, 29.62, 29.55, 29.42, 29.34, 29.09, 29.00, 28.95, 22.69, 14.11. IR(neat, cm-1) 3053, 2966, 1531, 1378, 1136, 1069, 840. HRMS(ESI) Calcd for C 45 H 55 O 5 SFNa 749.3652, Found 749.3646.

[0098] Colorless liquid 1h (30.0 mg, 41.4%). 1 1H NMR (400 MHz, CDCl 3 )δ7.41 (dd, J = 7.7, 1.4 Hz, 2H), 7.37–7.23 (m, 11H), 7.02 (dd, J = 6.9, 2.4 Hz, 2H), 6.87 (m, 2H), 6.80–6.74 (m, 1H), 6.16 (s, 1H), 4.70 (s, 2H), 4.58 (d, J = 12.1 Hz, 1H), 4.46 (d, J = 12.1 Hz, 1H), 4.38 (d, J = 11.6 Hz, 1H), 4.17 (d, J = 11.6 Hz, 1H), 4.09 (d, J = 2.2 Hz, 1H), 3.80 (dd, J = 7.4, 2.2 Hz, 1H), 3.61–3.49 (m, 3H), 2.32–1.87 (m, 2H), 1.47–1.07 (m, 20H), 0.88 (t, J = 6.8 Hz, 3H). 19 19F NMR (376 MHz, CDCl 3 )δ - 122.42 (td, J = 8.3, 4.1 Hz). 13 13C NMR (101 MHz, CDCl 3)δ158.99,156.62,155.18,138.12,137.54,128.43,128.35,128.31,128.19,127.93,127.83,1 27.75,127.58,127.54,116.29,116.05,112.22,111.97,110.67,109.70,109.62,80.04,74.95 ,73.65,73.38,71.76,71.47,69.95,58.28,31.92,29.63,29.56,29.42,29.35,29.11,29.01,2 8.27,22.69,14.12.IR(neat,cm-1)3053,2962,1528,1380,1136,1058,840.HRMS(EI)CalcdforC 45 H 55 O 5 SFNa749.3652,Found749.3650.

[0099] Example 5

[0100] Synthesis of compounds 1i and 1j:

[0101]

[0102] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-bromophenol (25.8 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and the mixture was washed with 10 mL of saturated sodium bicarbonate aqueous solution. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1i (19.8 mg, 25.2%). 1 H NMR (400 MHz, CDCl 3)δ7.79(d,J=2.2Hz,1H),7.48–7.43(m,2H),7.42–7.37(m,2H),7.36–7.22(m,10H),7.12–7. 06(m,2H),6.73(d,J=8.5Hz,1H),5.81(s,1H),5.10(d,J=10.8Hz,1H),4.96(d,J=10.8Hz,1H ),4.70(d,J=10.9Hz,1H),4.54–4.42(m,3H),3.99(d,J=9.4Hz,1H),3.82–3.73(m,1H),3.63 –3.51(m,2H),3.37(t,J=9.2Hz,1H),2.26(m,2H),1.45–1.11(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ157.62,138.23,137.93,137.76,132.48,130.93,128.75,128.45,128.39,128.35,12 7.97,127.90,127.81,127.79,127.75,127.65,113.93,111.85,110.54,83.47,76.88,7 5.70,74.86,73.51,69.69,60.85,31.92,29.63,29.56,29.43,29.35,29.10,29.00,28. 94,22.69,14.12.IR(neat,cm-1)3051,2962,1526,1380,1136,1069,582.HRMS(EI)Calcd for C 45 H 55 O 5 SBrNa 809.2851,Found 809.2849.

[0103] Colorless liquid 1j (29.7 mg, 37.8%). 1 H NMR (400 MHz, CDCl 3)δ7.42(dd,J=7.8,1.5Hz,2H),7.38–7.24(m,13H),7.06–7.00(m,2H),6.73(d ,J=8.4Hz,1H),6.16(s,1H),4.72(s,2H),4.59(d,J=12.1Hz,1H),4.46(d,J=12 .1Hz,1H),4.37(d,J=11.5Hz,1H),4.15–4.09(m,2H),3.78(dd,J=7.4,1.8Hz,1 H),3.57–3.49(m,3H),2.11(m,2H),1.46–1.10(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ158.43,138.10,137.47,132.51,128.74,128.46,128.32,128.26,128.18,127.98, 127.84,127.69,127.60,127.47,113.25,110.74,79.67,75.14,73.61,73.39,71.72, 71.33,69.96,57.72,31.93,29.64,29.57,29.42,29.35,29.11,29.02,28.98,28.31, 22.69,14.12.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,586.HRMS(EI)Calcd for C 45 H 55 O 5 SBrNa 809.2851,Found 809.2849.

[0104] Example 6

[0105] Synthesis of compounds 1k and 1l:

[0106]

[0107] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-methylphenol formate (22.8 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1k (14.8 mg, 19.3%). 1 H NMR (400 MHz, CDCl 3 )δ8.40(d,J=1.8Hz,1H),7.99(dd,J=8.5,1.9Hz,1H),7.50(d,J=7.1Hz,2H) ,7.44–7.20(m,10H),7.16(dd,J=7.1,2.4Hz,2H),7.06(dd,J=6.4,3.1Hz,2H ),6.87(d,J=8.5Hz,1H),5.93(s,1H),5.17(d,J=10.8Hz,1H),4.98(dd,J=1 1.0,3.4Hz,2H),4.85(d,J=10.8Hz,1H),4.67(d,J=10.8Hz,1H),4.60(dd,J= 14.1,11.7Hz,2H),4.54–4.46(m,3H),4.43–4.36(m,2H),4.04(d,J=9.4Hz, 1H),3.94(t,J=9.6Hz,1H),3.87(s,3H),3.83(m,2H),3.72(dd,J=10.8,1.9H z,1H),3.57(m,2H),3.33(t,J=9.2Hz,1H),2.69(m,2H),2.36(m,1H),2.18( m,1H),1.63(dd,J=15.0,7.4Hz,2H),1.46–1.10(m,20H),0.96–0.83(m,3H). 13 C NMR (101 MHz, CDCl 3) δ 198.95, 166.69, 162.09, 138.33, 137.92, 137.85, 137.73, 137.46, 132.42, 130.12, 128.45, 128.40, 128.36, 128.34, 128.27, 128.02, 127.98, 127.86, 127.79, 127.71, 127.64, 126.71, 124.26, 111.25, 110.07, 86.94, 84.51, 83.20, 78.79, 76.03, 75.19, 74.87, 73.99, 73.54, 73.47, 72.03, 69.88, 68.36, 60.05, 51.91, 31.92, 29.74, 29.63, 29.59, 29.54, 29.51, 29.42, 29.34, 29.09, 28.95, 28.66, 22.69, 14.12. IR (neat, cm-1) 3053, 2962, 1729, 1380, 1136, 1069, 840. HRMS (ESI) Calcd for C 47 H 58 O 7 SNa 789.3801, Found 789.3800.

[0108] Colorless liquid 1 l (29.6 mg, 38.7%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.97–7.91 (m, 2H), 7.44 (d, J = 6.5 Hz, 2H), 7.38–7.25 (m, 8H), 7.23–7.19 (m, 3H), 6.98 (dd, J = 6.4, 2.9 Hz, 2H), 6.88 (d, J = 8.7 Hz, 1H), 6.25 (s, 1H), 4.73 (q, J = 11.6 Hz, 2H), 4.58 (d, J = 12.1 Hz, 1H), 4.46 (d, J = 12.1 Hz, 1H), 4.35 (d, J = 11.5 Hz, 1H), 4.22 (d, J = 1.4 Hz, 1H), 4.09 (d, J = 11.5 Hz, 1H), 3.87 (d, J = 2.6 Hz, 3H), 3.77 (dd, J = 7.6, 1.5 Hz, 1H), 3.55–3.51 (m, 2H), 3.47 (dt, J = 11.3, 3.7 Hz, 1H), 2.25–2.14 (m, 1H), 1.97 (dt, J = 11.7, 7.5 Hz, 1H), 1.46–1.06 (m, 20H), 0.89 (t, J = 6.8 Hz, 3H). 13C NMR (101 MHz, CDCl 3 )δ166.44,163.06,138.08,137.52,137.40,132.32,128.31,128.45,128.32,128.25,128.23,127 .95,127.83,127.67,127.61,127.57,127.37,126.79,123.70,111.26,109.01,79.57,75.01,73. 65,73.38,71.52,71.32,69.98,57.14,51.93,31.92,29.63,29.55,29.40,29.35,29.10,29.03,2 8.99,28.38,22.69,14.12.IR(neat,cm-1)3053,2962,1718,1380,1136,1069,840.HRMS(EI)Calcd for C 47 H 58 O 7 SNa789.3801,Found 789.3797.

[0109] Example 7

[0110] Synthesis of compounds 1m and 1n:

[0111]

[0112] Add 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-cresol (4 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) to the reaction tube and react at 0°C for 24 hours. After the reaction is complete, add 5 mL of dichloromethane, wash with 10 mL of saturated sodium bicarbonate aqueous solution, dry the organic phase, spin dry, and obtain colorless liquid 1m (10.1 mg, 13.7%) by column chromatography. 1 H NMR (400 MHz, CDCl 3)δ9.82(s,1H),8.15(d,J=1.7Hz,1H),7.82(dd,J=8.4,1.8Hz,1H),7.48(d,J=7.0Hz,2H),7.43–7.20(m,11H),7.08(dd,J=6.6,2.9Hz,2H),6.94(d,J=8.3Hz,1H),5.95(s,1H),5.12(d,J=10.7Hz,1H),4.98(d,J=10.7Hz,1H),4.69(d,J=10.9Hz,1H),4.49(d,J=3.5Hz,2H),4.42(d,J=10.9Hz,1H),4.05(d,J=9.4Hz,1H),3.83(m,1H),3.61–3.51(m,2H),3.32(t,J=9.2Hz,1H),2.26(m,3H),1.43–1.11(m,20H),0.88(dd,J=7.8,5.9Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ190.65,163.27,138.10,137.86,137.66,132.15,131.57,130.99,128.49,128.39,128.34,127.94,127.90,127.84,127.67,111.29,110.91,83.01,76.17,74.85,73.48,69.78,59.79,31.91,29.60,29.53,29.40,29.33,29.08,28.93,28.90,22.67,14.10.IR(neat,cm-1)3052,2962,1658,1380,1136,1068,840.HRMS(ESI)Calcd forC 46 H 56 O 6 SNa 759.3695,Found 759.3688.

[0113] Colorless liquid 1n(30.3mg,41.2%). 1 H NMR(400MHz,CDCl 3)δ9.77(s,1H),7.73(s,1H),7.43(dd,J=7.8,1.5Hz,2H),7.38–7.24(m,9H),7.21(dd,J=4.9,1.7Hz,3H), 6.98–6.91(m,3H),6.26(s,1H),4.77–4.68(m,2H),4.58(d,J=12.1Hz,1H),4.46(d,J=12.1Hz,1H),4.28(d ,J=11.4Hz,1H),4.20(d,J=1.6Hz,1H),4.08(d,J=11.4Hz,1H),3.76(dd,J=7.6,1.7Hz,1H),3.52(dd,J=3 .9,2.2Hz,2H),3.44(dt,J=7.7,3.9Hz,1H),2.27–1.91(m,2H),1.40–1.05(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ190.25,164.19,138.01,137.36,137.23,133.42,131.03,128.50,128.34,128.06, 127.94,127.83,127.65,127.57,126.87,111.41,109.66,79.32,74.91,73.66,73.40 ,71.59,71.46,69.94,56.75,31.91,29.62,29.53,29.39,29.34,29.09,28.98,28.43 ,22.68,14.11.IR(neat,cm-1)3052,2964,1649,1380,1136,1069,840.HRMS(EI)Calcd for C 46 H 56 O 6 SNa 759.3695,Found759.3687.

[0114] Example 8

[0115] Synthesis of compounds 1o and 1p:

[0116]

[0117] 2 (63.2 mg, 0.1 mmol, 1 equiv), phenol (31.8 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1o (20.9 mg, 25.3%). 1 H NMR (400 MHz, CDCl 3 )δ7.62(d,J=2.1Hz,1H),7.39–7.09(m,18H),7.08–7.01(m,3H),6.73(d,J=8.4Hz,1H),5.83( s,1H),5.06(d,J=10.8Hz,1H),4.91(d,J=10.8Hz,1H),4.61(d,J=10.9Hz,1H),4.50(q,J=12.1 Hz,2H),4.39(d,J=10.9Hz,1H),3.98(d,J=9.4Hz,1H),3.79(m,1H),3.55(m,2H),3.28(t,J=9. 2Hz,1H),2.36–2.06(m,2H),1.61(d,J=6.0Hz,6H),1.39–1.09(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ156.44,151.07,144.31,138.64,138.12,137.76,128.35,128.32,128.14,127.90,127.85,127. 78,127.57,127.42,127.33,126.62,125.61,125.47,110.85,109.34,83.99,76.82,76.52,75.97,7 4.69,73.46,70.13,61.03,42.68,31.93,30.90,30.87,29.65,29.63,29.57,29.48,29.35,29.17,2 9.11,28.99,22.69,14.12.IR(neat,cm-1)3046,2961,1528,1382,1137,1069,840.HRMS(ESI)Calcd forC 54 H 66 O 5SNa 849.4529,Found 849.4519.

[0118] Colorless liquid 1p (41.8 mg, 50.7%). 1 H NMR (400 MHz, CDCl 3 )δ7.38(dd,J=7.8,1.5Hz,2H),7.35–7.08(m,18H),7.06–6.99(m,3H),6.75(d, J=8.4Hz,1H),6.14(s,1H),4.66–4.55(m,3H),4.46(d,J=12.1Hz,1H),4.32(d,J =11.8Hz,1H),4.16–4.09(m,2H),3.77(dd,J=8.1,2.2Hz,1H),3.62–3.48(m,3H) ,2.05(m,2H),1.57(d,J=2.8Hz,6H),1.42–1.08(m,20H),0.89(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ157.36,150.86,143.91,138.19,137.87,137.76,128.34,128.31,128.29,127.94,127.84,12 7.74,127.70,127.53,126.66,125.65,123.57,110.52,108.47,80.85,74.97,73.58,73.35,71.7 4,71.34,69.96,58.52,42.62,31.93,30.99,30.93,29.66,29.65,29.59,29.49,29.36,29.23,29 .12,28.40,22.70,14.13.IR(neat,cm-1)3051,2965,1528,1380,1136,1069,840.HRMS(EI)Calcd forC 54 H 66 O 5 SNa 849.4529,Found 849.4517.

[0119] Example 9

[0120] Synthesis of compounds 1q and 1r:

[0121]

[0122] 2 (63.2 mg, 0.1 mmol, 1 equiv), 2-cresol (16.2 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and the mixture was washed with 10 mL of saturated sodium bicarbonate aqueous solution. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1q (18.3 mg, 25.3%). 1 H NMR (400 MHz, CDCl 3 )δ7.52–7.44(m,3H),7.41–7.20(m,11H),7.08(dd,J=6.5,2.9Hz,2H),7.04(d,J=7.4Hz,1H),6.85(t,J=7.5Hz, 1H),5.85(s,1H),5.11(d,J=10.7Hz,1H),4.95(d,J=10.7Hz,1H),4.68(d,J=10.9Hz,1H),4.50(q,J=12.1Hz,2H) ,4.42(d,J=10.9Hz,1H),4.02(d,J=9.4Hz,1H),3.86–3.76(m,1H),3.58(dd,J=10.7,6.1Hz,1H),3.51(dd,J=10. 7,3.1Hz,1H),3.33(t,J=9.1Hz,1H),2.34(m,1H),2.26–2.16(m,4H),1.44–1.10(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ156.91,138.61,138.06,137.92,130.90,128.38,128.35,128.33,127.97,127.87,127. 82,127.73,127.65,127.59,125.41,125.32,121.76,120.12,110.14,83.67,76.12,74.72 ,73.46,70.09,61.28,31.93,29.64,29.57,29.45,29.36,29.34,29.14,29.11,28.99,22. 70,15.10,14.13.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,840.HRMS(ESI)Calcd for C 46 H58 O 5 SNa 745.3903,Found 745.3901.

[0123] Colorless liquid 1r (36.6 mg, 50.7%). 1 H NMR (400 MHz, CDCl 3 )δ7.44(d,J=6.7Hz,2H),7.37–7.22(m,11H),7.02(t,J=6.6Hz,4H),6.84(t,J= 7.5Hz,1H),6.17(s,1H),4.71(d,J=2.8Hz,2H),4.60(d,J=12.0Hz,1H),4.45(dd ,J=22.3,11.9Hz,2H),4.21–4.12(m,2H),3.82(dd,J=7.6,2.5Hz,1H),3.58(m, 3H),2.29–2.17(m,4H),2.00(m,1H),1.44–1.11(m,20H),0.89(t,J=6.8Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ157.68,138.24,137.83,137.80,130.83,128.39,128.29,128.23,128.15,127.96,127.84,127 .80,127.71,127.62,127.56,127.43,125.70,122.54,121.19,119.26,109.76,80.56,75.16,73. 67,73.33,71.65,71.37,69.98,58.66,31.93,29.64,29.58,29.45,29.36,29.23,29.12,29.05,2 8.38,22.70,15.22,14.12.IR(neat,cm-1)3052,2958,1526,1380,1137,1069,840.HRMS(EI)Calcd for C 46 H 58 O 5 SNa 745.3903,Found 745.3900.

[0124] Example 10

[0125] Synthesis of compounds 1s and 1t:

[0126]

[0127] 2 (63.2 mg, 0.1 mmol, 1 equiv), 2-tert-butylphenol (22.5 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1s (18.3 mg, 24%). 1 H NMR (400 MHz, CDCl 3 )δ7.57(dd,J=7.5,1.3Hz,1H),7.48(d,J=7.0Hz,2H),7.41–7.35(m,2H),7.35–7.21(m,7H),7.20–7.15(m,3H), 7.12–7.08(m,2H),6.91(t,J=7.7Hz,1H),5.87(s,1H),5.12(d,J=10.7Hz,1H),4.96(d,J=10.7Hz,1H),4.69(d, J=10.9Hz,1H),4.56–4.42(m,3H),4.01(d,J=9.5Hz,1H),3.79(m,1H),3.63(dd,J=10.9,5.9Hz,1H),3.51(dd,J =10.9,2.9Hz,1H),3.39(t,J=9.2Hz,1H),2.21(m,2H),1.36(s,9H),1.33–1.12(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ156.52,138.69,138.25,137.99,133.35,128.35,128.34,128.29,127.99,127.79,127.7 0,127.59,127.46,126.47,126.28,125.66,121.79,110.15,83.90,77.16,76.94,76.14,74 .71,73.35,69.83,60.86,33.99,31.92,29.62,29.56,29.44,29.36,29.26,29.19,29.07,2 8.99,22.69,14.11.IR(neat,cm-1)3051,2962,1526,1380,1136,1069,842.HRMS(ESI)Calcd for C 49 H64 O 5 SNa 787.4372,Found 787.4370.

[0128] Colorless liquid 1t (36.6 mg, 48%). 1 H NMR (400 MHz, CDCl 3 )δ7.46–7.41(m,2H),7.37–7.20(m,12H),7.13(dd,J=7.8,1.2Hz,1H),7.03(m,3H), 6.87(t,J=7.6Hz,1H),6.18(s,1H),4.70(q,J=11.6Hz,2H),4.54(d,J=12.1Hz,1H), 4.42(dd,J=26.2,11.9Hz,2H),4.17(dd,J=11.8,6.7Hz,2H),3.75–3.67(m,1H),3.5 3–3.44(m,3H),2.01(m,2H),1.37(s,9H),1.35–1.08(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ157.66,138.33,137.83,137.78,132.34,128.40,128.24,128.19,127.82,127.69,127.6 5,127.60,127.45,126.21,126.18,122.94,121.17,109.73,80.41,75.53,73.50,73.19,71 .39,71.21,70.24,58.11,34.09,31.94,29.63,29.58,29.45,29.36,29.10,29.07,29.03,2 8.25,22.70,14.13.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,842.HRMS(ESI)Calcd for C 49 H 64 O 5 SNa787.4372,Found 787.4368.

[0129] Embodiment 11

[0130] Synthesis of compounds 1u and 1v:

[0131]

[0132] Add 2 (63.2 mg, 0.1 mmol, 1 equiv), 2-fluorophenol (16.8 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) to the reaction tube and react at 0°C for 24 hours. After the reaction is complete, add 5 mL of dichloromethane, wash with 10 mL of saturated sodium bicarbonate aqueous solution, dry the organic phase, spin dry, and column chromatography to obtain a colorless liquid 1u (19.2 mg, 26.4%). 1 HNMR (400MHz, CDCl 3 )δ7.44(dd,J=10.6,3.9Hz,2H),7.42–7.21(m,12H),7.09(dd,J=6.5,2.9Hz,2H),7.00(dd,J=13.8,4. 7Hz,1H),6.88(td,J=8.0,4.4Hz,1H),5.94(s,1H),5.09(d,J=10.7Hz,1H),4.95(d,J=10.6Hz,1H),4.6 8(d,J=10.9Hz,1H),4.48(dt,J=17.4,11.5Hz,3H),4.01(d,J=9.5Hz,1H),3.84(m,1H),3.58(m,2H),3. 34(t,J=9.2Hz,1H),3.10(s,1H),2.29(m,2H),1.47–1.35(m,2H),1.26(m,18H),0.88(t,J=6.9Hz,3H). 19 FNMR (376MHz, CDCl 3 )δ-137.97(dd,J=10.2,4.1Hz). 13 CNMR (101MHz, CDCl 3)δ148.59,146.14,145.07,138.37,137.98,137.77,129.75,128.42,128.38,128.33,127.93,127.85,127.80,127.76,127.59,123.31,122.32,116.84,116.68,111.56,83.25,76.94,76.46,74.79,73.52,70.05,61.07,45.93,31.92,29.62,29.5429.42,29.34,29.29,29.08,28.94,22.69,14.11,8.70.IR(neat,cm-1)3051,2958,1528,1380,1136,1069,840.HRMS(ESI)CalcdforC 45 H 55 O 5 SFNa749.3652,Found749.3648.

[0133] Colorless liquid 1v(28.8mg,39.6%). 1 HNMR(400MHz,CDCl 3 )δ7.42(d,J = 6.7Hz,2H),7.37–7.22(m,11H),7.04–6.94(m,4H),6.85(td,J = 7.9,4.3Hz,1H),6.25(s,1H),4.70(s,2H),4.60(d,J = 12.0Hz,1H),4.47(d,J = 12.0Hz,1H),4.39(d,J = 11.7Hz,1H),4.17(dd,J = 14.6,6.9Hz,2H),3.86(dd,J = 7.7,2.1Hz,1H),3.60(m,3H),2.12(m,2H),1.47–1.10(m,20H),0.89(t,J = 6.8Hz,3H). 19 FNMR(376MHz,CDCl 3 )δ-137.29(dd,J = 10.4,4.2Hz). 13 CNMR(101MHz,CDCl 3)δ147.57,145.97,145.86,145.11,138.14,137.66,137.62,130.21,128.42,128.31,128.26,128.14 ,127.88,127.84,127.68,127.57,127.50,121.75,121.70,120.53,129.50,116.64,116.47,111.41,8 0.25,74.75,73.70,73.41,71.74,71.65,69.81,58.25,31.93,29.63,29.55,29.42,29.35,29.09,29 .00,28.35,22.69,14.11.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,840.HRMS(EI)CalcdforC 45 H 55 O 5 SFNa749.3652,Found749.3649.

[0134] Example 12

[0135] Synthesis of compounds 1w and 1x:

[0136]

[0137] Add 2 (63.2 mg, 0.1 mmol, 1 equiv), 2-chlorophenol (4 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) to the reaction tube and react at 0°C for 24 hours. After the reaction is complete, add 5 mL of dichloromethane, wash with 10 mL of saturated sodium bicarbonate aqueous solution, dry the organic phase, spin dry, and obtain a colorless liquid 1w (16.1 mg, 21.7%) by column chromatography. 1 HNMR (400MHz, CDCl 3)δ 7.53 (dd, J = 7.5, 1.0 Hz, 1H), 7.45 (d, J = 7.0 Hz, 2H), 7.41–7.20 (m, 12H), 7.09 (dd, J = 6.5, 2.9 Hz, 2H), 6.89 (t, J = 7.8 Hz, 1H), 5.96 (s, 1H), 5.08 (d, J = 10.6 Hz, 1H), 4.95 (d, J = 10.6 Hz, 1H), 4.66 (d, J = 10.9 Hz, 1H), 4.51 (dd, J = 27.7, 12.1 Hz, 2H), 4.42 (d, J = 10.9 Hz, 1H), 4.00 (d, J = 9.5 Hz, 1H), 3.86 (m, 1H), 3.60 (dd, J = 10.7, 6.0 Hz, 1H), 3.51 (dd, J = 10.7, 3.2 Hz, 1H), 3.31 (t, J = 9.1 Hz, 1H), 2.29 (m, 2H), 1.39 (dd, J = 14.9, 7.5 Hz, 2H), 1.26 (dd, J = 35.2, 15.0 Hz, 18H), 0.88 (t, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl 3 ) δ 154.31, 138.36, 138.00, 137.77, 129.90, 128.42, 128.37, 128.33, 128.11, 127.93, 127.88, 127.77, 127.59, 126.33, 122.73, 115.57, 111.02, 82.99, 74.73, 73.52, 70.14, 61.18, 31.92, 29.62, 29.54, 29.42, 29.34, 29.26, 29.08, 28.96, 28.93, 22.69, 14.11. IR (neat, cm-1) 3050, 2966, 1528, 1380, 1136, 1077, 840. HRMS (ESI) Calcd for C 45 H 55 O 5 SClNa 765.3356, Found 765.3348.

[0138] Colorless liquid 1x (32.2 mg, 43.3%). 1 1H NMR (400 MHz, CDCl 3)δ7.41(d,J=6.8Hz,2H),7.37–7.22(m,11H),7.19(d,J=7.9Hz,1H),7.08(d,J=7.4Hz,1H), 7.03–6.97(m,2H),6.85(t,J=7.8Hz,1H),6.24(s,1H),4.69(s,2H),4.60(d,J=12.0Hz,1H), 4.47(d,J=12.0Hz,1H),4.38(d,J=11.7Hz,1H),4.19(d,J=11.7Hz,1H),4.12(d,J=2.3Hz,1 H),3.91–3.84(m,1H),3.58(m,3H),2.12(m,2H),1.50–1.08(m,20H),0.89(t,J=6.8Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ154.96,138.14,137.65,137.59,129.76,128.59,128.42,128.30,128.26,128.16,127. 87,127.68,127.57,127.50,127.66,123.51,122.14,114.70,110.69,80.34,74.72,73.75, 73.39,71.72,69.73,58.57,31.92,29.63,29.55,29.42,29.35,29.09,29.04,29.00,28.39 ,22.69,14.12.IR(neat,cm-1)3053,2962,1528,1380,1136,1075,840.HRMS(EI)CalcdforC 45 H 55 O 5 SClNa765.3356,Found765.3352.

[0139] Embodiment 13

[0140] Synthesis of compounds 1y and 1z:

[0141]

[0142] 2 (63.2 mg, 0.1 mmol, 1 equiv), 2-methyl, 3-fluorophenol (18.9 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1y (24.6 mg, 33.2%). 1 HNMR (400MHz, CDCl 3 )δ7.46(d,J=6.9Hz,2H),7.43–7.22(m,12H),7.09(dd,J=6.5,2.9Hz,2H),6.70–6.55(m ,1H),5.89(s,1H),5.09(d,J=10.7Hz,1H),4.95(d,J=10.7Hz,1H),4.69(d,J=10.9Hz,1 H),4.49(dt,J=14.9,11.5Hz,3H),3.99(d,J=9.4Hz,1H),3.82(m,1H),3.54(m,2H),3.3 2(t,J=9.1Hz,1H),2.29(m,2H),2.11(s,3H),1.46–1.12(m,20H),0.89(t,J=6.9Hz,3H). 19 FNMR (376MHz, CDCl 3 )δ-117.12–-117.26(m). 13 CNMR (101MHz, CDCl 3 )δ163.49,161.06,158.08,157.98,138.47,137.97,137.82,128.42,128.37,128.35,127.98,127. 84,127.82,127.79,127.73,127.65,125.34,125.24,120.95,111.01,108.57,108.34,83.38,77.1 0,76.84,76.27,74.73,73.46,70.01,60.85,31.92,29.63,29.56,29.45,29.34,29.31,29.11,28. 99,22.69,14.12,7.80.IR(neat,cm-1)3046,2963,1528,1382,1136,1068,840.HRMS(EI)Calcdfor C46 H 57 O 5 SFNa 763.3808, Found 763.3810.

[0143] Colorless liquid 1z (36.9 mg, 49.8%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.42 (d, J = 6.4 Hz, 2H), 7.37–7.23 (m, 11H), 7.02 (dd, J = 6.5, 2.9 Hz, 2H), 6.93 (dd, J = 8.3, 5.4 Hz, 1H), 6.63–6.54 (m, 1H), 6.18 (s, 1H), 4.70 (s, 2H), 4.59 (d, J = 12.0 Hz, 1H), 4.47 (d, J = 12.1 Hz, 1H), 4.38 (d, J = 11.7 Hz, 1H), 4.17 (d, J = 11.7 Hz, 1H), 4.12 (d, J = 2.2 Hz, 1H), 3.83–3.75 (m, 1H), 3.55 (dd, J = 9.6, 4.4 Hz, 3H), 2.26–2.13 (m, 4H), 2.01 (m, 1H), 1.46–1.09 (m, 20H), 0.89 (t, J = 6.9 Hz, 3H). 19 FNMR (376 MHz, CDCl 3 ) δ -116.88– -117.06 (m). 13 CNMR (101 MHz, CDCl 3 ) δ 163.30, 160.87, 158.82, 158.72, 138.16, 137.69, 137.66, 128.41, 128.30, 128.28, 128.17, 127.86, 127.83, 127.70, 127.57, 127.53, 122.49, 121.24, 110.72, 108.17, 107.92, 107.60, 107.38, 80.34, 75.03, 73.64, 73.36, 71.66, 71.43, 69.95, 58.23, 31.92, 29.63, 29.57, 29.44, 29.35, 29.19, 29.13, 29.04, 28.39, 22.69, 14.12, 7.92, 7.88. IR (neat, cm-1) 3050, 2961, 1527, 1380, 1135, 1069, 840. HRMS (EI) Calcd for C 46 H 57 O 5SFNa763.3808,Found763.3802.

[0144] Embodiment 14

[0145] Synthesis of compounds 1aa and 1ab:

[0146]

[0147] 2 (63.2 mg, 0.1 mmol, 1 equiv), 2-methyl, 3-chlorophenol (21.3 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1aa (26.3 mg, 34.8%). 1 HNMR (400MHz, CDCl 3 )δ7.47–7.42(m,2H),7.41–7.21(m,12H),7.08(dd,J=6.6,2.9Hz,2H),6.95(d,J=8.1Hz,1H), 5.87(s,1H),5.08(d,J=10.7Hz,1H),4.94(d,J=10.7Hz,1H),4.68(d,J=10.9Hz,1H),4.48(dt ,J=17.7,11.5Hz,3H),3.99(d,J=9.5Hz,1H),3.81(m,1H),3.54(m,2H),3.31(t,J=9.2Hz,1H) ,2.35(dt,J=11.7,7.3Hz,1H),2.28–2.17(m,4H),1.45–1.11(m,20H),0.88(t,J=6.9Hz,3H). 13 CNMR (101MHz, CDCl 3) δ 157.65, 138.42, 137.96, 137.78, 135.41, 128.42, 128.36, 127.99, 127.83, 127.74, 127.65, 125.50, 124.16, 122.55, 119.10, 110.67, 83.39, 76.86, 76.24, 74.74, 73.48, 69.99, 61.07, 31.92, 29.62, 29.56, 29.44, 29.34, 29.11, 29.08, 28.96, 22.68, 14.10, 12.52. IR (neat, cm-1) 3050, 2962, 1528, 1380, 1138, 1092, 840. HRMS (ESI) Calcd for C 46 H 57 O 5 SClNa 779.3513, Found 779.3509.

[0148] Colorless liquid 1ab (39.5 mg, 52.2%). 1 1H NMR (400 MHz, CDCl 3 ) δ 7.42 (dd, J = 7.8, 1.5 Hz, 2H), 7.37–7.23 (m, 12H), 7.01 (dd, J = 6.5, 2.9 Hz, 2H), 6.92 (s, 2H), 6.17 (s, 1H), 4.69 (s, 2H), 4.58 (d, J = 12.1 Hz, 1H), 4.47 (d, J = 12.1 Hz, 1H), 4.38 (d, J = 11.7 Hz, 1H), 4.17 (d, J = 11.7 Hz, 1H), 4.11 (d, J = 2.3 Hz, 1H), 3.80 (dd, J = 7.6, 2.2 Hz, 1H), 3.60–3.51 (m, 3H), 2.28 (s, 3H), 2.25–1.95 (m, 2H), 1.45–1.09 (m, 20H), 0.89 (t, J = 6.9 Hz, 3H). 13 13C NMR (101 MHz, CDCl 3)δ158.36,138.14,137.65,137.62,135.21,128.42,128.30,128.17,128.88,127.83,127.71 ,127.58,127.54,124.43,122.69,122.01,118.28,110.33,80.23,74.99,73.69,73.38,71.7 0,71.49,69.98,58.39,31.93,29.64,29.58,29.44,29.35,29.15,29.13,29.02,28.39,22.6 9,14.11,12.64.IR(neat,cm-1)3053,2962,1528,1382,1136,1091,840.HRMS(ESI)CalcdforC 46 H 57 O 5 SClNa779.3513,Found779.3511.

[0149] Embodiment 15

[0150] Synthesis of compounds 1ac and 1ad:

[0151]

[0152] 2 (63.2 mg, 0.1 mmol, 1 equiv), 2,3-dimethylphenol (18.3 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and the mixture was washed with 10 mL of saturated sodium bicarbonate aqueous solution. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1ac (26.9 mg, 36.5%). 1 HNMR (400MHz, CDCl 3)δ 7.49–7.44 (m, 2H), 7.41–7.20 (m, 12H), 7.08 (dd, J = 6.6, 3.0 Hz, 2H), 6.75 (d, J = 7.7 Hz, 1H), 5.83 (s, 1H), 5.12 (d, J = 10.7 Hz, 1H), 4.94 (d, J = 10.8 Hz, 1H), 4.68 (d, J = 10.9 Hz, 1H), 4.56–4.39 (m, 3H), 4.01 (d, J = 9.4 Hz, 1H), 3.80 (m, 1H), 3.56 (m, 2H), 3.33 (t, J = 9.1 Hz, 1H), 2.34 (m, 1H), 2.29–2.18 (m, 4H), 2.12 (s, 3H), 1.43–1.09 (m, 20H), 0.88 (t, J = 6.9 Hz, 3H). 13 13C NMR (101 MHz, CDCl 3 ) δ 157.13, 138.69, 138.57, 138.09, 137.95, 128.34, 128.34, 128.32, 127.96, 127.87, 127.78, 127.71, 127.61, 127.57, 124.57, 123.29, 122.84, 118.78, 110.14, 83.78, 76.02, 74.74, 73.46, 70.13, 61.53, 31.93, 29.64, 29.59, 29.47, 29.36, 29.20, 29.14, 29.01, 22.70, 19.54, 14.12, 11.69. IR (neat, cm-1) 3048, 2956, 1528, 1380, 1132, 1055, 840. HRMS (ESI) Calcd for C 47 H 60 O 5 SNa 759.4059, Found 759.4049.

[0153] Colorless liquid 1ad (26.9 mg, 36.5%). 1 1H NMR (400 MHz, CDCl 3)δ7.46–7.41(m,2H),7.39–7.22(m,11H),7.04(dd,J=6.5,3.0Hz,2H),6.92(d,J=7.6Hz,1H), 6.73(d,J=7.7Hz,1H),6.14(s,1H),4.70(d,J=4.7Hz,2H),4.59(d,J=12.0Hz,1H),4.45(dd,J= 20.3,11.9Hz,2H),4.17(dd,J=10.3,7.0Hz,2H),3.84–3.77(m,1H),3.61–3.52(m,3H),2.24(s ,3H),2.23–2.17(m,1H),2.16(s,3H),2.02(m,1H),1.46–1.06(m,20H),0.89(t,J=6.9Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ157.91,138.50,138.27,137.90,137.82,128.37,128.28,128.23,128.13,127.85,127.76, 127.63,127.51,123.09,122.75,121.73,117.89,109.75,80.67,75.28,73.61,73.33,71.67,7 1.33,70.00,58.96,31.93,29.65,29.60,29.46,29.35,29.29,29.14,29.06,28.42,22.69,19 .62,14.12,11.78.IR(neat,cm-1)3052,2962,1528,1380,1136,1058,840.HRMS(EI)CalcdforC 47 H 60 O 5 SNa759.4059,Found759.4051.

[0154] Example 16

[0155] Synthesis of compounds 1ae and 1af:

[0156]

[0157] 2 (63.2 mg, 0.1 mmol, 1 equiv), 3-chloro, 4-methylphenol (21.3 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1ae (23.8 mg, 31.5%). 1 HNMR (400MHz, CDCl 3 )δ7.50–7.44(m,3H),7.42–7.22(m,11H),7.09(m,2H),6.85(s,1H),5.82(s,1H),5.10(d,J=10 .7Hz,1H),4.96(d,J=10.7Hz,1H),4.69(d,J=10.8Hz,1H),4.55–4.41(m,3H),3.99(d,J=9.4Hz ,1H),3.78(m,1H),3.57(m,2H),3.34(t,J=9.2Hz,1H),2.37(dt,J=11.6,7.3Hz,1H),2.28(s,3 H),2.24–2.12(m,1H),1.39(dd,J=14.9,7.3Hz,2H),1.34–1.10(m,18H),0.88(t,J=6.8Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ157.16,138.45,137.96,137.81,134.86,129.62,129.15,128.39,128.33,127.9 3,127.90,127.78,127.64,125.07,111.00,110.79,83.37,75.92,74.82,73.52,69. 90,60.65,31.92,29.62,29.57,29.44,29.34,29.27,29.12,29.02,28.95,22.69,19 .91,14.11.IR(neat,cm-1)3051,2956,1528,1380,1136,1090,840.HRMS(ESI)Calcd forC 46 H 57 O 5 SClNa779.3513,Found779.3511.

[0158] Colorless liquid 1af (23.8 mg, 31.5%). 1 HNMR (400MHz, CDCl 3 )δ7.43(d,J=7.0Hz,2H),7.38–7.20(m,11H),6.98(s,3H),6.86(s,1H),6. 15(s,1H),4.72(s,2H),4.60(d,J=12.0Hz,1H),4.47(d,J=12.1Hz,1H),4.3 3(d,J=11.6Hz,1H),4.17–4.09(m,2H),3.78(d,J=7.2Hz,1H),3.58–3.47(m ,3H),2.31–2.15(m,4H),1.98(m,1H),1.31(m,20H),0.88(t,J=6.4Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ158.08,138.13,137.60,134.77,128.63,128.44,128.30,128.24,127.93,127.84,12 7.66,127.58,127.30,126.75,110.70,110.00,79.82,75.14,73.52,73.39,71.43,71.25 ,70.01,57.68,31.92,29.63,29.58,29.42,29.34,29.13,29.07,28.99,28.31,22.69,1 9.65,14.11.IR(neat,cm-1)3053,2962,1516,1377,1136,1093,840.HRMS(EI)CalcdforC 46 H 57 O 5 SClNa779.3513,Found779.3509.

[0159] Embodiment 17

[0160] Synthesis of compounds 1ag and 1ah:

[0161]

[0162] 2 (63.2 mg, 0.1 mmol, 1 equiv), 3-fluoro, 4-methylphenol (18.9 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1ag (22.6 mg, 30.5%). 1 HNMR (400MHz, CDCl 3 )δ7.50–7.22(m,14H),7.14–7.07(m,2H),6.53(d,J=9.6Hz,1H),5.84(s,1H),5.11(d,J=10.7 Hz,1H),4.96(d,J=10.7Hz,1H),4.70(d,J=10.8Hz,1H),4.49(dt,J=23.3,11.5Hz,3H),3.99( d,J=9.4Hz,1H),3.79(ddd,J=8.9,5.8,3.1Hz,1H),3.58(ddd,J=13.8,10.7,4.5Hz,2H),3.35 (t,J=9.2Hz,1H),2.37(m,1H),2.23–2.12(m,4H),1.45–1.13(m,20H),0.88(t,J=6.9Hz,3H). 19 FNMR (376MHz, CDCl 3 )δ-113.89(t,J=7.9Hz). 13 CNMR (101MHz, CDCl 3)δ163.22, 160.67, 157.55, 157.42, 138.51, 137.99, 137.86, 129.90, 129.84, 128.38, 128.32, 127.92, 127.88, 127.80, 127.72, 127.62, 121.43, 117.71, 111.02, 98.38, 98.10, 83.38, 77.15, 76.76, 75.97, 74.79, 73.50, 69.96, 60.58, 31.92, 29.63, 29.57, 29.44, 29.34, 29.24, 29.12, 29.06, 28.97, 22.68, 14.48, 14.44, 14.11. IR(neat, cm-1) 3052, 2968, 1528, 1378, 1136, 1032, 840. HRMS(ESI) Calcd for C 46 H 57 O 5 SFNa 763.3808, Found 763.3811.

[0163] Colorless liquid 1ah (22.6 mg, 30.5%). 1 H NMR(400 MHz, CDCl 3 )δ7.46–7.42(m, 2H), 7.38–7.23(m, 11H), 7.00(dd, J=6.8, 2.5 Hz, 2H), 6.93(d, J=7.6 Hz, 1H), 6.54(d, J=9.7 Hz, 1H), 6.17(s, 1H), 4.73(s, 1H), 4.60(d, J=12.1 Hz, 1H), 4.47(d, J=12.1 Hz, 1H), 4.35(d, J=11.5 Hz, 1H), 4.15(dd, J=6.6, 4.9 Hz, 2H), 3.79(dd, J=7.5, 1.6 Hz, 1H), 3.57–3.48(m, 3H), 2.26–2.20(m, 1H), 2.14(d, J=1.8 Hz, 3H), 2.04–1.93(m, 1H), 1.47–1.12(m, 20H), 0.89(t, J=6.9 Hz, 2H). 19 F NMR(376 MHz, CDCl 3 )δ - 113.69– - 113.89(m). 13 C NMR(101 MHz, CDCl 3)δ162.98,160.54,158.47,158.34,138.16,137.66,137.64,128.43,128.31,128.30,128.23,127.97,127 .91,127.84,127.76,127.66,127.58,127.33,127.04,126.97,121.40,117.53,117.34,112.28,110.94,9 7.31,97.04,79.95,75.21,73.48,73.38,71.41,71.21,70.03,57.69,31.93,29.64,29.58,29.43,29.35, 29.13,29.03,28.31,22.69,14.12.IR(neat,cm-1)3054,2962,1528,1380,1136,1036,840.HRMS(EI)Calcd for C 46 H 57 O 5 SFNa 763.3808,Found 763.3806.

[0164] Embodiment 18

[0165] Synthesis of compounds 1ai and 1aj:

[0166]

[0167] 2 (63.2 mg, 0.1 mmol, 1 equiv), phenol (22.2 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1ai (25.9 mg, 34%). 1 H NMR (400 MHz, CDCl 3)δ 7.47 (d, J = 6.9 Hz, 2H), 7.40–7.20 (m, 12H), 7.08 (dd, J = 6.5, 3.0 Hz, 2H), 6.67 (d, J = 7.8 Hz, 1H), 5.86 (s, 1H), 5.12 (d, J = 10.8 Hz, 1H), 4.94 (d, J = 10.8 Hz, 1H), 4.72–4.65 (m, 1H), 4.51 (q, J = 12.1 Hz, 2H), 4.42 (d, J = 10.9 Hz, 1H), 4.00 (d, J = 9.4 Hz, 1H), 3.83 (m, 1H), 3.55 (m, 2H), 3.33 (t, J = 9.1 Hz, 1H), 2.74 (s, 2H), 2.61 (s, 2H), 2.30 (m, 2H), 1.76 (s, 4H), 1.39 (dd, J = 15.0, 7.4 Hz, 2H), 1.33–1.11 (m, 18H), 0.88 (t, J = 6.9 Hz, 3H). 13 13C NMR (101 MHz, CDCl 3 )δ 156.48, 139.19, 138.70, 138.12, 137.96, 128.35, 128.32, 127.97, 127.87, 127.78, 127.69, 127.59, 127.56, 124.38, 122.47, 121.99, 119.97, 110.52, 83.55, 77.35, 77.03, 76.71, 76.29, 74.69, 73.46, 70.30, 61.26, 31.93, 29.64, 29.59, 29.48, 29.42, 29.35, 29.30, 29.25, 29.14, 29.03, 22.97, 22.82, 22.69, 22.44, 14.12. IR (neat, cm-1) 3052, 2962, 1533, 1380, 1136, 1068, 840. HRMS (ESI) Calcd for C 49 H 62 O 5 SNa 785.4216, Found 785.4212.

[0168] Colorless liquid 1aj (51.8 mg, 51%). 1 1H NMR (400 MHz, CDCl 3) δ 7.43 (d, J = 6.6 Hz, 2H), 7.37–7.21 (m, 8H), 7.05 (dd, J = 6.5, 2.9 Hz, 2H), 6.98 (t, J = 7.8 Hz, 1H), 6.92 (d, J = 7.7 Hz, 1H), 6.67 (dd, J = 12.6, 7.7 Hz, 2H), 6.60 (d, J = 7.9 Hz, 1H), 6.15 (s, 1H), 4.71 (q, J = 11.5 Hz, 2H), 4.60 (d, J = 12.0 Hz, 1H), 4.45 (dd, J = 18.4, 11.8 Hz, 2H), 4.18 (dd, J = 9.5, 7.0 Hz, 2H), 3.82 (dd, J = 7.4, 1.9 Hz, 1H), 3.61–3.54 (m, 3H), 2.75 (dd, J = 11.4, 5.4 Hz, 2H), 2.65 (dd, J = 12.0, 5.7 Hz, 2H), 2.28–1.98 (m, 2H), 1.88–1.72 (m, 4H), 1.44–1.09 (m, 20H), 0.89 (t, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 157.30, 153.49, 139.14, 138.92, 138.24, 137.90, 137.81, 128.38, 128.33, 128.29, 128.25, 128.14, 127.88, 127.77, 127.66, 127.53, 125.98, 123.30, 122.22, 122.03, 121.52, 119.18, 111.78, 109.93, 80.65, 75.30, 73.62, 73.35, 71.69, 71.30, 69.97, 58.78, 31.94, 29.65, 29.60, 29.49, 29.39, 29.36, 29.16, 29.10, 28.46, 22.93, 22.80, 22.78, 22.73, 22.70, 22.40, 14.13. IR (neat, cm-1) 3053, 2962, 1522, 1380, 1138, 1059, 840. HRMS (EI) Calcd for C 49 H 62 O 5 SNa 785.4216, Found 785.4210.

[0169] Example 19

[0170] Synthesis of Compounds 1ak and 1al:

[0171]

[0172] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-phenylphenol (25.5 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1ak (20.6 mg, 26.3%). 1 HNMR (400MHz, CDCl 3 )δ7.97(d,J=2.0Hz,1H),7.49(m,5H),7.42–7.20(m,14H),7.09(dd,J=6.6,2.9Hz,2H ),6.91(d,J=8.3Hz,1H),5.88(s,1H),5.15(d,J=10.5Hz,1H),4.99(d,J=10.5Hz,1H), 4.70(d,J=10.9Hz,1H),4.56–4.41(m,4H),4.06(d,J=9.4Hz,1H),3.81(m,1H),3.60( m,2H),3.40(t,J=9.2Hz,1H),2.30(m,2H),1.43–1.08(m,20H),0.88(t,J=6.9Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ158.14,140.72,138.56,138.02,137.83,134.92,128.69,128.39,128.36,128.32,127 .98,127.91,127.81,127.76,127.59,126.91,126.72,126.65,110.78,110.34,83.71,75. 76,74.86,73.51,69.96,60.91,31.91,29.71,29.61,29.55,29.43,29.33,29.10,28.95,2 2.68,14.11.IR(neat,cm-1)3053,2962,1528,1366,1132,1069,840.HRMS(ESI)CalcdforC 51 H 60 O 5 SNa807.4059,Found807.4051.

[0173] Colorless liquid 1al (41.2 mg, 52.7%). 1 HNMR (400MHz, CDCl 3 )δ7.49–7.21(m,18H),7.19–7.10(m,1H),7.04(t,J=7.5Hz,2H),6.92(dd,J=8.0 ,6.5Hz,2H),6.22(s,1H),4.77(s,1H),4.66–4.45(m,4H),4.37(d,J=11.4Hz,1H ),4.25(d,J=10.4Hz,1H),4.13(d,J=11.4Hz,1H),3.81(dd,J=13.3,5.0Hz,2H), 3.62–3.51(m,3H),2.38–1.94(m,2H),1.45–1.03(m,20H),0.88(t,J=6.8Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ159.07,140.86,138.18,137.73,137.51,134.89,128.76,128.68,128.52,128.43,128.30,128. 21,128.16,127.86,127.56,127.36,126.86,127.76,123.99,110.60,109.33,81.45,80.31,75.39 ,73.63,73.39,71.68,71.32,70.00,58.15,31.92,29.62,29.56,29.42,29.34,29.19,29.11,29.0 1,28.41,22.69,14.11.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,840.HRMS(EI)Calcdfor C 51 H 60 O 5 SNa807.4059,Found807.4051.

[0174] Embodiment 20

[0175] Synthesis of compounds 1am and 1an:

[0176]

[0177] 2 (63.2 mg, 0.1 mmol, 1 equiv), 4-bromobiphenol (37.2 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1am (20.9 mg, 24.3%). 1 H NMR (400 MHz, CDCl 3 )δ7.90(d,J=2.0Hz,1H),7.52–7.35(m,8H),7.34–7.20(m,10H),7.10(dd,J=6.6,2.9Hz, 2H),6.90(d,J=8.4Hz,1H),5.89(s,1H),5.14(d,J=10.4Hz,1H),4.99(d,J=10.4Hz,1H), 4.72(d,J=10.8Hz,1H),4.60–4.40(m,3H),4.06(d,J=9.4Hz,1H),3.80(m,1H),3.67–3.5 3(m,2H),3.39(t,J=9.2Hz,1H),2.31(m,2H),1.45–1.06(m,20H),0.88(t,J=6.9Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ158.39,139.61,138.50,137.98,137.79,133.63,131.74,128.43,128.39,128.33,128. 18,128.12,127.96,127.91,127.87,127.79,127.62,127.13,126.72,120.86,110.75,110. 50,83.63,75.68,74.88,73.52,69.89,60.81,31.92,29.63,29.56,29.44,29.38,29.34,29 .09,22.69,14.12.IR(neat,cm-1)3056,2965,1528,1382,1138,1069,659.HRMS(ESI)Calcd for C 51 H 59 O 5 SBrNa 885.3164,Found 885.3138.

[0178] Colorless liquid 1an (41.8 mg, 48.7%). 1 H NMR (400 MHz, CDCl 3 )δ7.50–7.43(m,4H),7.39–7.14(m,13H),7.07(t,J=7.5Hz,2H),6.96–6.89(m,2H ),6.22(s,1H),4.77(s,2H),4.61(d,J=12.1Hz,1H),4.48(d,J=12.1Hz,1H),4.34( d,J=11.4Hz,1H),4.25(d,J=1.5Hz,1H),4.13(d,J=11.4Hz,1H),3.85–3.78(m,1H) ,3.60–3.54(m,2H),2.33–1.94(m,2H),1.45–1.09(m,20H),0.88(t,J=6.9Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ159.31,139.79,138.14,137.67,137.45,133.61,131.73,128.58,128.44,128.38,128.32,128.27,128 .24,128.17,128.02,127.91,127.86,127.79,127.65,127.60,127.33,127.07,123.82,120.88,110.59,10 9.47,80.25,75.39,73.65,73.41,71.68,71.39,70.01,58.01,31.92,29.63,29.57,29.42,29.35,29.16,2 9.10,28.98,28.41,22.69,14.12.IR(neat,cm-1)3053,2962,1528,1380,1136,1069,661.HRMS(ESI)Calcd for C 51 H 59 O 5 SBrNa 863.3345,Found 863.3310.

[0179] Embodiment 21

[0180] Synthesis of compounds 1ao and 1ap:

[0181]

[0182] 2 (63.2 mg, 0.1 mmol, 1 equiv), phenol (37.2 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1ao (27.6 mg, 32%). 1 H NMR (400 MHz, CDCl 3 )δ7.68(s,1H),7.44(t,J=7.0Hz,3H),7.40–7.18(m,10H),7.17(d,J=8.6Hz,2 H),7.08(dd,J=6.5,3.0Hz,2H),6.99(d,J=8.1Hz,1H),6.73(d,J=8.7Hz,2H),5 .90(s,1H),5.06(dd,J=13.2,10.9Hz,2H),4.93(d,J=10.7Hz,1H),4.67(d,J=1 0.9Hz,1H),4.57(dd,J=21.0,9.8Hz,3H),4.50(dd,J=11.9,4.5Hz,2H),4.44(d ,J=2.4Hz,1H),4.38(t,J=10.5Hz,1H),4.25(d,J=10.7Hz,1H),4.01(d,J=4.0H z,1H),3.97(d,J=9.5Hz,1H),3.79(d,J=3.3Hz,2H),3.70(s,3H),3.49–3.40(m ,2H),3.29(t,J=9.2Hz,1H),2.64–2.55(m,2H),2.19(ddt,J=85.4,11.6,7.4Hz ,2H),1.48(dd,J=15.2,7.9Hz,2H),1.39–1.10(m,20H),0.88(t,J=6.8Hz,3H). 13 C NMR (101 MHz, CDCl 3)δ190.69,165.29,157.92,157.69,138.39,138.05,137.77,137.37,137.22,135.11,131.35,129.54,128.52,128.44,128.37,128.33,128.09,127.98,127.82,127.76,127.59,126.29,124.78,123.08,122.45,113.67,111.18,109.75,83.38,81.44,77.22,76.91,74.79,74.55,74.41,73.70,73.43,70.03,67.86,61.03,55.14,34.06,31.92,31.77,29.65,29.60,29.55,29.44,29.35,29.32,29.22,29.13,28.95,28.53,22.69,14.11.IR(neat,cm-1)3053,2968,1524,1380,1136,1093,840.HRMS(ESI)Calcd for C 53 H 63 O 5 SClNa 885.3932,Found 885.3884.

[0183] Colorless liquid 1ap (27.6 mg, 32%). 1 1H NMR (400 MHz, CDCl 3 )δ7.41 (d, J = 7.4 Hz, 2H), 7.37–7.16 (m, 14H), 7.01–6.97 (m, 2H), 6.94 (d, J = 1.1 Hz, 1H), 6.74 (d, J = 8.7 Hz, 2H), 6.20 (s, 1H), 4.69 (d, J = 3.6 Hz, 1H), 4.56 (d, J = 12.1 Hz, 1H), 4.46 (d, J = 12.1 Hz, 1H), 4.44–4.38 (m, 1H), 4.33 (d, J = 11.8 Hz, 1H), 4.12 (dd, J = 9.7, 6.8 Hz, 2H), 4.05 (d, J = 4.6 Hz, 2H), 3.76 (dd, J = 7.6, 1.6 Hz, 1H), 3.70 (s, 3H), 3.48 (td, J = 8.6, 3.9 Hz, 2H), 2.24–1.86 (m, 2H), 1.46–1.08 (m, 20H), 0.89 (t, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl 3)δ158.53,157.92,138.15,137.57,134.89,131.40,129.59,128.42,128.34,128.31,128.29,128.23,128.1 3,127.91,127.79,127.72,127.61,127.57,127.53,124.83,123.43,122.54,121.69,113.72,113.68,110.7 1,79.87,74.98,73.55,73.34,71.50,71.33,69.99,58.25,55.14,31.90,29.66,29.65,29.59,29.46,29.37 ,29.14,29.04,28.29,22.70,14.12.IR(neat,cm-1)3053,2962,1527,1378,1136,1092,840.HRMS(EI)Calcd for C 53 H 63 O 5 SClNa 885.3932,Found 885.3912.

[0184] Embodiment 22

[0185] Synthesis of compounds 1aq and 1ar:

[0186]

[0187] 2 (63.2 mg, 0.1 mmol, 1 equiv), phenol (39.3 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1aq (21.4 mg, 24.4%). 1 H NMR (400 MHz, CDCl 3) δ 7.46–7.18 (m, 14H), 7.15 (d, J = 8.6 Hz, 2H), 7.07 (dd, J = 6.5, 2.9 Hz, 2H), 6.98 (d, J = 8.1 Hz, 1H), 6.72 (d, J = 8.7 Hz, 2H), 5.90 (s, 1H), 5.06 (dd, J = 12.4, 11.0 Hz, 1H), 4.93 (d, J = 10.7 Hz, 1H), 4.67 (d, J = 10.9 Hz, 1H), 4.57 (dd, J = 21.0, 9.8 Hz, 2H), 4.44 (d, J = 3.6 Hz, 1H), 4.38 (t, J = 10.8 Hz, 1H), 4.25 (d, J = 10.7 Hz, 1H), 4.00 (d, J = 4.9 Hz, 1H), 3.96 (d, J = 9.5 Hz, 1H), 3.91 (m, 2H), 3.79 (m, 2H), 3.43 (m, 2H), 3.29 (t, J = 9.2 Hz, 1H), 2.63–2.56 (m, 1H), 2.19 (m, 2H), 1.51–1.09 (m, 23H), 0.88 (t, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 165.30, 157.30, 138.40, 138.06, 137.77, 135.12, 131.19, 129.52, 128.53, 128.44, 128.37, 128.32, 127.97, 127.83, 127.76, 127.58, 127.78, 126.27, 124.75, 123.07, 122.48, 114.26, 111.21, 83.35, 81.44, 74.79, 74.42, 73.70, 73.43, 70.07, 67.85, 63.28, 61.01, 34.06, 31.92, 29.66, 29.59, 29.45, 29.35, 29.22, 29.14, 28.96, 22.69, 14.87, 14.12. IR (neat, cm-1) 3053, 2962, 1528, 1380, 1136, 1093, 842. HRMS (ESI) Calcd for C 54 H 65 O 5 SClNa 899.4088, Found 899.4073.

[0188] Colorless liquid 1ar (42.1 mg, 36.6%). 1 H NMR (400 MHz, CDCl 3)δ7.43–7.38(m,2H),7.29(m,12H),7.19(d,J=8.6Hz,2H),6.98(dd,J=6.5,2.9Hz,2H),6.93(d,J=1.0Hz,1H),6 .72(d,J=8.7Hz,2H),6.19(s,1H),4.68(d,J=3.6Hz,1H),4.55(d,J=12.1Hz,1H),4.44(d,J=12.1Hz,1H),4.32(d ,J=11.8Hz,1H),4.12(dd,J=10.4,6.8Hz,2H),4.04(s,2H),3.91(q,J=7.0Hz,2H),3.76(dd,J=7.6,1.7Hz,1H),3 .47(td,J=8.6,3.7Hz,3H),2.20–1.85(m,2H),1.34(t,J=7.0Hz,3H),1.31–1.10(m,20H),0.88(t,J=6.8Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ158.53,157.28,138.15,137.57,134.89,131.24,129.55,128.42,128.30,128.28,128.22,127 .90,127.78,127.70,127.55,127.52,124.79,123.40,122.53,121.72,114.26,110.71,79.86,74. 97,73.53,73.33,71.39,69.98,63.28,58.24,31.93,29.64,29.60,29.46,29.36,29.14,29.04,2 8.28,22.69,14.86,14.12.IR(neat,cm-1)3050,2962,1527,1380,1137,1094,840.HRMS(EI)Calcd for C 54 H 65 O 5 SClNa 899.4088,Found 899.4060.

[0189] Embodiment 23

[0190] Synthesis of compounds 1as and 1at:

[0191]

[0192] 2 (63.2 mg, 0.1 mmol, 1 equiv), phenol (38.7 mg, 0.15 mmol, 1.5 equiv), TFAA (45 ul, 0.3 mmol, 3 equiv), 2,6-Lutidine (34.9 ul, 0.3 mmol, 3 equiv) and dichloromethane (1 mL) were added to the reaction tube and reacted at 0°C for 24 hours. After the reaction was complete, 5 mL of dichloromethane was added, and 10 mL of saturated sodium bicarbonate aqueous solution was washed. The organic phase was dried, spin-dried, and column chromatography was performed to obtain a colorless liquid 1as (29.6 mg, 34%). 1 H NMR (400 MHz, CDCl 3 )δ7.66(d,J=7.8Hz,1H),7.59(d,J=7.6Hz,1H),7.51–7.43(m,3H),7.41–7.31(m,3H),7.29–7.19(m,8H),7.17–7.11(m,2H),7.09– 7.04(m,2H),7.02(s,1H),6.74–6.65(m,1H),5.99(s,1H),5.08(d,J=10.7Hz,1H),4.94(d,J=10.7Hz,1H),4.67(d,J=10.9Hz,1H),4 .41(d,J=10.9Hz,1H),4.35(d,J=12.1Hz,1H),4.24(d,J=12.1Hz,1H),4.18(s,2H),3.96(d,J=9.5Hz,1H),3.88–3.80(m,1H),3.46( dd,J=10.7,6.3Hz,1H),3.37(dd,J=10.6,3.1Hz,1H),3.30(t,J=9.2Hz,1H),2.23m,2H),1.43–1.09(m,20H),0.89(t,J=6.8Hz,3H). 19 F NMR (376 MHz, CDCl 3 )δ-117.67. 13 C NMR (101 MHz, CDCl 3)δ162.97, 160.52, 157.58, 143.16, 139.62, 138.40, 138.03, 137.77, 128.42, 128.35, 128.27, 127.96, 127.87, 127.77, 127.69, 127.53, 127.06, 126.96, 124.08, 123.60, 122.93, 122.06, 121.79, 121.48, 112.10, 110.53, 110.32, 108.98, 108.75, 82.99, 74.76, 73.25, 70.34, 60.63, 31.93, 29.65, 29.63, 29.56, 29.42, 29.36, 29.12, 28.96, 24.13, 22.69, 14.12. IR(neat, cm-1) 3044, 2967, 1531, 1382, 1136, 1056, 840. HRMS(ESI) Calcd for C 54 H 61 O 5 S 2 FNa 895.3842, Found 895.3816.

[0193] Colorless liquid 1 at (29.6 mg, 34%). 1 1H NMR(400 MHz, CDCl 3 )δ7.65(d, J = 7.7 Hz, 1H), 7.58(d, J = 7.6 Hz, 1H), 7.41(d, J = 6.5 Hz, 2H), 7.37–7.18(m, 13H), 7.05(s, 1H), 7.00(dd, J = 8.3, 5.0 Hz, 3H), 6.68–6.60(m, 1H), 6.24(s, 1H), 4.73–4.63(m, 2H), 4.53(d, J = 12.1 Hz, 1H), 4.42(d, J = 12.1 Hz, 1H), 4.34(d, J = 11.8 Hz, 1H), 4.23(s, 2H), 4.17–4.09(m, 2H), 3.78(dd, J = 7.5, 1.7 Hz, 1H), 3.55–3.43(m, 3H), 2.25–1.87(m, 2H), 1.42–1.01(m, 20H), 0.89(t, J = 6.8 Hz, 3H). 19 19F NMR(376 MHz, CDCl 3 )δ -117.65. 13 13C NMR(101 MHz, CDCl 3)δ158.54,143.07,139.96,139.67,138.14,137.61,137.58,128.42,128.29,128.27,128.22,127 .90,127.80,127.69,127.55,127.49,124.01,123.55,122.90,122.04,121.46,111.37,108.35,79 .97,74.97,73.54,73.31,71.51,71.32,69.90,58.04,31.93,29.63,29.59,29.41,29.36,29.12,2 9.06,28.32,22.69,14.12.IR(neat,cm-1)3049,2960,1535,1380,1136,1053,840.HRMS(EI)Calcd for C 54 H 61 O 5 S 2 FNa 895.3842,Found 895.3820.

[0194] Embodiment 24

[0195] Synthesis of compound 5:

[0196]

[0197] 4 (1.01 g, 1 equiv), m-chloroperbenzoic acid (m-CPBA) (613 mg, 0.15 mmol, 2.2 equiv), and dichloromethane (20 mL) were added to the reaction tube and reacted at 0°C for 2 hours. After the reaction was complete, 50 mL of dichloromethane was added, and the mixture was washed with 100 mL of saturated sodium bicarbonate aqueous solution. The organic phase was dried and spin-dried for the next step. The crude product was dissolved in 20 mL of tetrahydrofuran, potassium hydroxide (208 mg, 2 equiv) was added, and the mixture was reacted at 60°C for 5 hours. After the reaction was complete, 50 mL of ethyl acetate was added, and the mixture was washed with 100 mL of water. The organic phase was dried and spin-dried, and column chromatography gave a white solid 5 (859 mg, 85%). 1 HNMR (400MHz, CDCl 3)δ7.38(d,J=8.4Hz,1H),7.35–7.21(m,18H),6.75(d,J=8.7Hz,2H),4.79–4.60(m,6H),4.52(s,2H),4.29(q,J=1 4.6Hz,2H),4.11(t,J=3.9Hz,1H),4.02–3.81(m,4H),3.74(dd,J=10.8,4.3Hz,1H),1.35(dd,J=11.1,4.1Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ157.43,152.68,137.97,137.83,137.66,137.52,135.62,131.02,130.92,129.71,129.35, 128.55,128.47,128.38,128.02,127.96,127.93,127.86,127.82,127.73,127.68,124.19,12 4.01,119.29,117.36,114.62,114.39,78.51,74.44,73.43,72.70,71.58,71.11,67.94,63.3 6,31.78,14.88.IR(neat,cm-1)3051,2983,1543,1382,1138,1095,663.HRMS(ESI)CalcdforC 42 H 39 O 6 ClNa697.2333,Found697.2331.

[0198] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the attached claims.

Claims

1. A method for synthesizing a sulfur-containing benzodihydrofuran structure carbon glycoside compound, characterized in that: The sulfur-containing sugar ene shown in formula (2) and the phenol compound shown in formula (3) are used as reaction raw materials, and under the action of an activation reagent and a base, in an organic solvent, a reaction is carried out to obtain a sulfur-containing benzodihydrofuran structure carbon glycoside compound shown in formula (1), and the reaction process is shown in reaction formula (a); in, R is selected from hydrogen, alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from halogen-substituted phenyl; the substituted benzyl is selected from alkoxy-substituted benzyl and benzothiophene benzyl.

2. The synthesis method according to claim 1, characterized in that The R is selected from hydrogen, C1-C15 alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted C1-C15 alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from 4-bromophenyl; the substituted benzyl is selected from 4-methoxybenzyl, 4-ethoxybenzyl, 2-benzothiophene benzyl.

3. The synthesis method according to claim 1, characterized in that In reaction formula (a), the molar ratio of the sulfur-containing sugar ene represented by formula (2) to the phenol compound represented by formula (3) is 1:(1-2); and / or the molar ratio of the activation reagent, the base and the sulfur-containing sugar ene is (1.5-10):(1.5-10):

1.

4. The synthesis method according to claim 1, characterized in that In reaction formula (a), the activation reagent is selected from one or more of trifluoroacetic anhydride, acetic anhydride, trifluoromethanesulfonic anhydride, trimethylsilyl chloride, trifluoromethanesulfonic anhydride trimethyl silicone, perfluoropropionic anhydride, and perfluorobutyric anhydride; and / or, the base is selected from one or more of potassium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, pyridine, 2,6-lutidine, 2,4,6-trimethylpyridine, triethylamine, diisopropylethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); and / or, the organic solvent is selected from one or more of dichloromethane, tetrahydrofuran, nitromethane, toluene, chloroform, and acetone.

5. The synthesis method according to claim 1, characterized in that In reaction formula (a), the reaction temperature is -10 to 60° C.; and / or the reaction time is 8 to 24 hours.

6. A method for synthesizing a benzofuran structure carbonyl glycoside compound, characterized in that: The sulfur-containing glycoside shown in formula (4) is used as a reaction raw material, and under the action of an oxidant and a base, a benzofuran structure glycoside compound shown in formula (5) is reacted in an organic solvent. The reaction process is shown in reaction formula (b): in, R is selected from hydrogen, alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from halogen-substituted phenyl; the substituted benzyl is selected from alkoxy-substituted benzyl and benzothiophene benzyl.

7. The synthesis method according to claim 6, characterized in that The R is selected from hydrogen, C1-C15 alkyl, halogen, ester, aldehyde, aryl, substituted aryl, polysubstituted C1-C15 alkyl halogen, cycloalkyl, substituted benzyl, 2-methylenethiophene; wherein the substituted aryl is selected from 4-bromophenyl; the substituted benzyl is selected from 4-methoxybenzyl, 4-ethoxybenzyl, 2-benzothiophene benzyl.

8. The synthesis method according to claim 6, characterized in that In reaction formula (b), the oxidant is selected from one or more of hydrogen peroxide, oxygen, 2,3-dichloro-5,6-dicyanobenzoquinone DDQ, and m-chloroperbenzoic acid m-CPBA; and / or the base is selected from one or more of potassium carbonate, cesium carbonate, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, pyridine, 2,6-lutidine, 2,4,6-trimethylpyridine, triethylamine, diisopropylethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene DBU; and / or the organic solvent is selected from one or more of dichloromethane, tetrahydrofuran, nitromethane, toluene, chloroform, and acetone.

9. The synthesis method according to claim 6, characterized in that In reaction formula (b), the reaction temperature is -10 to 60° C.; and / or the reaction time is 8 to 24 hours.

10. The synthesis method according to claim 6, characterized in that In reaction formula (b), the molar ratio of the oxidant, the base and the sulfur-containing glycoside is (1.5-10): (1.5-10): 1.

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