Preparation method of alanine containing sulfonyl

Abstract

The invention belongs to the technical field of compound synthesis, and particularly relates to a preparation method of alanine containing sulfonyl. The preparation method comprises the step of mixing and reacting a sulfonyl-containing free radical compound, a hydrogen atom donor and dehydroalanine to prepare sulfonyl-containing alanine. According to the preparation method, sulfur can be introduced into amino acid, the conversion rate can reach 93%, reaction conditions are mild, raw materials are easy to obtain, and peculiar smell is avoided; in addition, the product is obtained only through one-step reaction, the reaction process is simple and efficient, and industrial production is facilitated.

Description

Technical Field

[0001] The invention belongs to the technical field of compound synthesis, and particularly relates to a method for preparing sulfonyl alanine. Background Art

[0002] Sulfur compounds are a common raw material for drug synthesis. For example, thiourea can be used to synthesize sulfathiazole, which has a broad-spectrum antibacterial effect. For example, cysteine ​​can be prepared into drugs such as antioxidants, detoxification and immune enhancement. For example, thiophene pyridine derivatives can be prepared into antiplatelet aggregation drugs such as clopidogrel. Therefore, with more and more approved organosulfur drugs, many researchers are currently trying to install sulfur elements in organic molecules.

[0003] Sulfur-containing amino acids are one of the research and development directions for installing sulfur elements in organic molecules, such as sulfonylalanine. The existing preparation method of sulfonylalanine requires the use of thiol / phenol, specifically including: dehydroalanine as the starting material, using thiol / phenol as the sulfur donor, then performing an addition reaction through Michael addition, and finally oxidizing the sulfur atom into sulfone to obtain sulfonylalanine; during the preparation process, thiol / phenol has a strong malodor that makes people uncomfortable and pollutes the environment, so research and development and production are subject to certain restrictions.

[0004] Therefore, it is necessary to develop a method for preparing sulfonylalanine-containing amino acids which avoids using raw materials having a foul odor. Summary of the invention

[0005] The present invention generates a carbon radical intermediate by addition of a sulfonyl radical to dehydroalanine, and then extracts hydrogen from a hydrogen atom donor by hydrogen atom transfer (HAT) to obtain a target product. The method introduces sulfur into amino acids to prepare sulfonylalanine, and avoids the stench caused by the use of thiol / phenol in the preparation process.

[0006] In order to achieve the above object, the present invention can adopt the following technical solutions:

[0007] The present invention provides a method for preparing sulfonyl alanine, comprising: reacting a sulfonyl radical compound, a hydrogen atom donor and dehydroalanine to obtain the sulfonyl alanine.

[0008] Preferably, the structural formula of the sulfonylalanine-containing amino acid is R is selected from an aromatic group or a first alkyl group.

[0009] More preferably, the aromatic group comprises a substituted or unsubstituted aromatic hydrocarbon group and / or a substituted or unsubstituted aromatic heterocyclic group; or the first alkyl group comprises a linear alkyl group or a cycloalkyl group.

[0010] More preferably, in the above aromatic groups: the substituted or unsubstituted aromatic hydrocarbon group is phenyl, biphenyl, triphenyl, naphthyl, binaphthyl, anthracenyl or phenanthryl; and / or the substituted or unsubstituted aromatic heterocyclic group is furanyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, coumarin, carbazolyl, phenanthridinyl, phenazinyl, phenoxazinyl or phenothiazinyl;

[0011] In the first alkyl group, the number of carbon atoms in the linear alkyl group is ≤10; or the number of ring atoms in the cycloalkyl group is ≤6.

[0012] More preferably, in the above-mentioned aromatic groups: the substituents of the substituted aromatic hydrocarbon group or the substituted aromatic heterocyclic group are independently selected from one or more of a second alkyl group, a halogen, a carboxyl group, an alkoxy group, a cyano group, a nitro group, a carbonyl group, a hydroxyl group or an amino group; in the above-mentioned first alkyl group: the straight-chain alkyl group is a n-pentyl group; or the cycloalkyl group is a cyclopropyl group.

[0013] More preferably, the second alkyl group is a linear alkyl group or a cycloalkyl group; or the halogen is selected from fluorine, chlorine or bromine.

[0014] More preferably, in the second alkyl group, the carbon number of the linear alkyl group is ≤10; or the ring atom number of the cycloalkyl group is ≤6.

[0015] Preferably, the sulfonyl radical-containing compound is obtained by catalysis of a compound containing a sulfonyl chloride group; and / or the hydrogen atom donor is tri(trimethylsilyl)silane; and / or the preparation method of dehydroalanine comprises: mixing phthalimide and triphenylphosphine in a solvent, and adding methyl propionate dropwise at 0°C-4°C to obtain dehydroalanine.

[0016] More preferably, the compound containing a sulfonyl chloride group is R-SO2-Cl.

[0017] More preferably, the above catalytic conditions include: catalysis using a catalyst under light conditions.

[0018] More preferably, the catalyst is a ruthenium-containing catalyst, Ir(ppy)3 or 4CzIPN.

[0019] More preferably, the catalyst is [Ru(bpz)3][PF6]2 or Ru(bpy)3(Cl)2·6H2O.

[0020] The beneficial effects of the present invention include: the preparation method of sulfonylalanine provided by the present invention can introduce sulfur into amino acids, the conversion rate can reach more than 93%, and the reaction conditions are mild, the raw materials are easy to obtain, no thiol / phenol is used, and there is no odor; in addition, the product is obtained by only one-step reaction, and the reaction process is simpler and more efficient than the existing method, which is more conducive to industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a schematic diagram of the reaction mechanism of the preparation method of the present invention;

[0022] Figure 2 Compound A prepared in Example 1 1 HNMR spectra;

[0023] Figure 3 Compound A prepared in Example 1 13 C NMR spectra;

[0024] Figure 4 Compound B prepared in Example 2 1 HNMR spectra;

[0025] Figure 5 Compound B prepared in Example 2 13 C NMR spectra;

[0026] Figure 6 Compound C prepared in Example 3 1 H NMR spectra;

[0027] Figure 7 Compound C prepared in Example 3 13 C NMR spectra;

[0028] Figure 8 Compound D prepared in Example 4 1 H NMR spectra;

[0029] Fig. 9 Compound D prepared in Example 4 13 C NMR spectrum. DETAILED DESCRIPTION

[0030] The examples are provided to better illustrate the present invention, but the present invention is not limited to the examples. Therefore, those skilled in the art may make non-essential improvements and adjustments to the implementation scheme according to the above invention content, which still fall within the protection scope of the present invention.

[0031] The terms used herein are only used to describe specific embodiments and are not intended to limit the present disclosure. Unless the context has a significantly different meaning, expressions in the singular include expressions in the plural. As used herein, it should be understood that terms such as "include", "have", "include" are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials or combinations. The terms of the present invention are disclosed in the specification, and are not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials or combinations thereof may exist or may be added. As used herein, " / " may be interpreted as "and" or "or", depending on the circumstances.

[0032] The terms "first", "second" or "third" etc. in the present invention are only used to distinguish the described objects and do not have any order or technical meaning.

[0033] The embodiment of the present invention provides a method for preparing sulfonyl alanine, comprising: reacting a sulfonyl radical compound, a hydrogen atom donor and dehydroalanine to obtain the sulfonyl alanine.

[0034] Specifically, the sulfonyl radical in the present invention reacts with dehydroalanine to generate a carbon radical intermediate, which is then combined with a hydrogen atom donor to generate the final product, namely, sulfonyl alanine. Figure 1 The reaction mechanism diagram shown is Figure 1 In the equation, PC is [Ru(bpz)3][PF6]2, that is,

[0035] In some specific examples, the structural formula of the sulfonyl alanine-containing amino acid is R may be selected from an aromatic group or a first alkyl group.

[0036] In some specific examples, the aromatic group includes a substituted or unsubstituted aromatic hydrocarbon group and / or a substituted or unsubstituted aromatic heterocyclic group; or the first alkyl group includes a linear alkyl group or a cycloalkyl group.

[0037] In some specific examples, in the above aromatic groups: the substituted or unsubstituted aromatic hydrocarbon group is phenyl, biphenyl, triphenyl, naphthyl, binaphthyl, anthracenyl or phenanthryl; and / or the substituted or unsubstituted aromatic heterocyclic group is furanyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, coumarin, carbazolyl, phenanthridinyl, phenazinyl, phenoxazinyl or phenothiazinyl;

[0038] In some specific examples, among the above-mentioned first alkyl groups, when a straight-chain alkyl group is selected, the number of carbon atoms in the straight-chain alkyl group can be ≤10, such as methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl, etc.; in addition, it also includes branched butyl groups (such as isobutyl and sec-butyl), branched pentyl groups, branched hexyl groups, branched heptyl groups, branched octyl groups, branched nonyl groups or branched n-decyl groups, etc.; when a cycloalkyl group is selected, the number of ring atoms in the cycloalkyl group can be ≤6, such as cyclopropyl, cyclobutyl or cyclopentyl, etc.; similarly, the cyclopropyl, cyclobutyl or cyclopentyl groups can also be connected to branches.

[0039] In some specific examples, in the above aromatic groups: the substituents of the substituted aromatic hydrocarbon group or the substituted aromatic heterocyclic group can be independently selected from one or more of a second alkyl group, a halogen, a carboxyl group, an alkoxy group, a cyano group, a nitro group, a hydroxyl group or an amino group.

[0040] Specifically, the above “independently selected from” means that the substituents of the substituted aromatic hydrocarbon group or the substituted aromatic heterocyclic group are selected independently and do not interfere with each other, and the substituents of the two groups can be the same or different. In addition, the number of substituents can be one or more, such as 2, 3, 4 or 5.

[0041] In some specific examples, in the first alkyl group: the straight-chain alkyl group is preferably n-pentyl; or the cycloalkyl group is preferably cyclopropyl.

[0042] In some specific examples, the second alkyl group is a linear alkyl group or a cycloalkyl group; or the halogen is selected from fluorine, chlorine or bromine.

[0043] In some specific examples, in the second alkyl group, the carbon number of the linear alkyl group is ≤10; or the ring atom number of the cycloalkyl group is ≤6.

[0044] Specifically, the type of the second alkyl group can be the same as the first alkyl group. Of course, in the same sulfonyl alanine, the second alkyl group can be the same as the first alkyl group or different from the first alkyl group.

[0045] In some specific examples, the sulfonyl radical-containing compound is obtained by catalysis of a sulfonyl chloride group-containing compound.

[0046] Specifically, the above-mentioned sulfonyl radical-containing compound can be prepared by all methods known in the art, preferably, it can be prepared by catalysis of a compound containing a sulfonyl chloride group; in addition, the compound containing a sulfonyl chloride group can be obtained commercially, which can avoid the stench of thiol / phenol used in other synthesis methods.

[0047] In some specific examples, the compound containing a sulfonyl chloride group is R-SO2-Cl.

[0048] Specifically, it should be understood that R in R-SO2-Cl is are the same, the choice of R in R-SO2-Cl is the same R.

[0049] In some specific examples, the above-mentioned catalytic conditions include: catalysis using a catalyst under light conditions.

[0050] Specifically, visible light is generally selected for illumination, and blue light can generally be selected.

[0051] In some specific examples, the catalyst is a ruthenium-containing catalyst.

[0052] In some specific examples, the catalyst is a ruthenium-containing catalyst, Ir(ppy)3 or 4CzIPN.

[0053] In some specific examples, the catalyst is [Ru(bpz)3][PF6]2 or Ru(bpy)3(Cl)2·6H2O.

[0054] Specifically, the catalyst in the present invention is preferably [Ru(bpz)3][PF6]2, which has a better catalytic effect.

[0055] In some specific examples, the hydrogen atom donor is tris(trimethylsilyl)silane.

[0056] In some specific examples, the preparation method of the above dehydroalanine includes: mixing phthalimide and triphenylphosphine in a solvent, and adding methyl propionate dropwise at 0° C.-4° C. to obtain dehydroalanine.

[0057] In some specific examples, the present invention can utilize sulfonyl chloride to generate a sulfonyl radical by single electron transfer (SET) under the action of blue light and a catalyst, which is then added with dehydroalanine to generate a carbon radical intermediate, and finally combined with a hydrogen atom donor to generate the final product, i.e., sulfonyl alanine.

[0058] In some specific examples, the reaction formula for preparing sulfonyl alanine by using a compound containing a sulfonyl chloride group and dehydroalanine in the present invention is as follows:

[0059]

[0060] In order to better understand the present invention, the content of the present invention is further explained below in conjunction with specific examples, but the content of the present invention is not limited to the following examples.

[0061] In the following examples, dehydroalanine is used Synthesized according to the following synthetic route:

[0062]

[0063] The specific synthesis method is as follows:

[0064] Phthalimide (1.49 g, 10.1 mmol, 1.01 equiv.), triphenylphosphine (1.05 g, 4 mmol, 0.4 equiv.) and 1,4-dioxane (20 mL) were added to a round-bottom flask equipped with a stirrer; the mixture was placed in an ice bath; methyl propionate (840.7 mg, 10 mmol, 1 equiv.) was then added dropwise over 30 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature; the reaction was monitored by TLC; after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and separated and purified by silica gel column chromatography (PE: EA = 4: 1), and dehydroalanine was finally obtained as a light yellow solid with a yield of 78%.

[0065] In the following example, the prepared sulfonylalanine-containing detection conditions include: characterization using 600 Hz nuclear magnetic resonance spectroscopy (Bruker AVANCE III 600), using deuterated chloroform as solvent for dissolution; using tetramethylsilane (TMS) as an internal standard; the prepared sulfonylalanine-containing nuclear magnetic resonance data report is as follows: 1 In HNMR chemical shift, the unit is δ; peak shape: s = singlet, d = doublet, t = triplet, m = multiplet, coupling constant J (unit is Hz); 13 CNMR data were reported as chemical shifts; the compounds were further confirmed by high-resolution mass spectrometry (HRMS, instrument model Vanquishflex+oribitrapexploris120, ThermoScientific).

[0066] 1. Optimization of preparation conditions of sulfonylalanine

[0067] 3a was prepared from compounds 1a and 2a according to the following synthetic route:

[0068]

[0069] The specific preparation method is as follows:

[0070] In a glove box, dehydroalanine (1a) (1 equiv.), 3-fluorobenzenesulfonyl chloride (2a), a hydrogen atom donor (HAD) and a solvent were added to a dry round-bottom flask, and then a photocatalyst was added. The reaction was carried out at room temperature (25°C) under the irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 4:1 to 3:1) as the eluent, to finally obtain compound 3a, and the yield was calculated.

[0071] Different hydrogen atom donors, different photocatalysts, and different reactant equivalents and reaction times were selected to prepare the target compound 3a, and the yield was calculated. The specific situation is shown in Table 1 below.

[0072] Table 1 Yields under different reaction conditions

[0073]

[0074] In Table 1 above, the structures of catalysts PC1 to PC1 are as follows:

[0075]

[0076] The structural formulas of hydrogen atom donors HAD to HAD5 are shown below:

[0077]

[0078] As shown in Table 1, 1.5 equivalents of HAD1 were used as hydrogen donors and the reaction was carried out under blue light (λ max =470nm) irradiation for 6 hours was used to screen commonly used photocatalysts, among which PC3 showed the best performance and obtained the target product with a yield of 53%, but the raw material reaction was not sufficient. Trying to increase the amount of 2a and the hydrogen donor, the yield continued to increase to 64%; in addition, reducing the equivalent of the catalyst and increasing the reaction concentration, the sulfonylalanine product can be completely reacted with a yield of 79%; in addition, the control test of the effect of solvent type on the experiment showed that 0.16M acetonitrile still had the best effect (compared to entries 8 to 11); then several common hydrogen donors were screened again, but the reaction effects were not as good as HAD1 (compared to entries 12 to 15); above, the present invention determined that under room temperature conditions, 2.5 equivalents of 2a (3-fluorobenzenesulfonyl chloride), 2.0 equivalents of hydrogen atom donor HAD1, 1.0 mol% photocatalyst PC3, irradiated with blue light (λmax=470nm) for 6 hours in 0.16M acetonitrile were the optimal reaction conditions.

[0079] 2. Preparation and characterization of sulfonylalanine

[0080] Example 1

[0081] In the embodiment of the present invention, the specific structural formula of the sulfonylalanine (also referred to as compound A) is:

[0082] The specific preparation method of compound A is as follows:

[0083] In a glove box, dehydroalanine (46.2 mg, 0.2 mmol, 1 equiv.), 3-fluorobenzenesulfonyl chloride (97.3 mg, 0.5 mmol, 2.5 equiv.), tris(trimethylsilyl)silane (99.5 mg, 0.2 mmol, 2 equiv.) and acetonitrile (1.2 mL) were added to a dry round-bottom flask, and then a photocatalyst [Ru(bpz)3][PF6]2 (1.7 mg, 1% mol) was added. The mixture was reacted at room temperature (25°C) for 6 hours under irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 4:1 to 3:1) as the eluent, to finally obtain compound A as a white solid with a calculated yield of 82% and a purity of 98%.

[0084] The structural characterization data of the obtained compound A are as follows: 1 HNMR(600MHz, CDCl3)δ7.82-7.80(m,2H),7.75-7.73(m,2H),7.65-7.63(m ,1H),7.55-7.53(dt,J1=7.8,J2=2.4Hz,1H),7.40(td,J1=8.4,J2=5.4Hz,1 H),7.12(td,J1=8.4,J2=2.4Hz,1H),5.37(dd,J=11.4,2.4Hz,1H),4.31(dd ,J1=15.6,J2=11.4Hz,1H),4.00(dd,J1=15.6,J2=2.4Hz,1H),3.73(s,3H); 13CNMR(150MHz,CDCl3)δ167.14,166.92,163.25-161.57(d,J=251.85Hz),1 40.55-140.51(d,J=6.45Hz),134.64,131.50,131.42-131.37(d,J=7.65H z),124.13-124.11(d,J=3.3Hz),123.89,121.29-121.15(d,J=21Hz),115.78-115.62(d,J=24.3Hz),53.89,53.10,46.85ppm; HRMS-ESI(m / z)calcd for[C 18 H 14 FNNaO6S] + ,414.0418;found,414.0427.

[0085] In addition, the obtained compound A 1 HNMR Figure 2 As shown, 13 C NMR Figure 3 shown.

[0086] Example 2

[0087] In the embodiment of the present invention, the specific structural formula of the sulfonylalanine (also referred to as compound B) is: The preparation method of compound B is as follows:

[0088] In a glove box, dehydroalanine (46.2 mg, 0.2 mmol, 1 equiv.), 5-bromothiophene-2-sulfonyl chloride (130.8 mg, 0.5 mmol, 2.5 equiv.), tris(trimethylsilyl)silane (99.5 mg, 0.2 mmol, 2 equiv.) and acetonitrile (1.2 mL) were added to a dry round-bottom flask, and then [Ru(bpz)3][PF6]2 (1.7 mg, 1% mol) was added, and the mixture was reacted at room temperature (25°C) for 6 hours under irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 4:1 to 3:1) as the eluent, to finally obtain compound B as a white solid with a calculated yield of 84% and a purity of 99%.

[0089] The structural characterization data of the obtained compound B are as follows: 1HNMR (600MHz, CDCl3) δ7.87-7.85(m,2H),7.77-7.75(m,2H),7.46(d,J=4.2Hz,1H),6.98(d,J=4.2Hz,1H),5.37( dd, J1=11.4, J2=2.4Hz, 1H), 4.33 (dd, J1=15.0, J2=11.4Hz, 1H), 4.06 (dd, J1=15.6, J2=2.4Hz, 1H), 3.75 (s, 3H); 13 C NMR (150MHz, CDCl3) δ167.07,167.06,139.78,135.78,134.72,131.61,131.16,123.98,123.35,54.50,53.93,47.01ppm; HRMS-ESI(m / z)calcd for[C 16 H 12 BrNNaO6S2] + ,479.9182;found,479.9189.

[0090] In addition, the obtained compound B 1 HNMR Figure 4 As shown, 13 C NMR Figure 5 shown.

[0091] Example 3

[0092] In the embodiment of the present invention, the specific structural formula of the sulfonylalanine (also referred to as compound C) is:

[0093] The preparation method of compound C is as follows:

[0094] In a glove box, dehydroalanine (46.2 mg, 0.2 mmol, 1 equiv.), p-propanesulfonyl chloride (70.3 mg, 0.5 mmol, 2.5 equiv.), tris(trimethylsilyl)silane (99.5 mg, 0.2 mmol, 2 equiv.) and acetonitrile (1.2 mL) were added to a dry round-bottom flask, and then a photocatalyst [Ru(bpz)3][PF6]2 (1.7 mg, 1% mol) was added. The mixture was reacted at room temperature (25°C) for 6 hours under irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 4:1 to 3:1) as the eluent, to finally obtain compound C as a white solid with a calculated yield of 93% and a purity of 98%.

[0095] The structural characterization data of the obtained compound C are as follows: 1 HNMR (600MHz, CDCl3) δ7.89-7.88(m,2H),7.76-7.75(m,2H),5.55(dd,J1=11.4,J2=3.0Hz,1H),4.06(dd,J1=15.0,J2=11.4Hz, 1H),3.93(dd,J1=15.0,J2=3Hz,1H),3.78(s,3H),2.48-2.45(m,1H),1.33-1.30(m,1H),1.19-1.16(m,1H),1.05-1.01(m,2H); 13 C NMR (150MHz, CDCl3) δ167.62,167.16,134.62,131.81,124.05,53.84,51.11,46.29,29.92,5.14,5.12ppm; HRMS-ESI(m / z)calcd for[C 15 H 15 NNaO6S] + ,360.0512;found,360.0521.

[0096] In addition, the obtained compound C 1 HNMR Figure 6 As shown, 13 C NMR Figure 7 shown.

[0097] Example 4

[0098] In the embodiment of the present invention, the specific structural formula of the sulfonylalanine (also referred to as compound D) is:

[0099] The preparation method of compound D is as follows:

[0100] In a glove box, dehydroalanine (46.2 mg, 0.2 mmol, 1 equiv.), 4-n-pentylbenzenesulfonic acid chloride (123.4 mg, 0.5 mmol, 2.5 equiv.), tris(trimethylsilyl)silane (99.5 mg, 0.2 mmol, 2 equiv.) and acetonitrile (1.2 mL) were added to a dry round-bottom flask, and then [Ru(bpz)3][PF6]2 (1.7 mg, 1% mol) was added. The mixture was reacted at room temperature (25°C) for 6 hours under irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 4:1 to 3:1) as the eluent, to finally obtain compound D as a white solid with a calculated yield of 65% and a purity of 96%.

[0101] The structural characterization data of the obtained compound D are as follows: 1 H NMR (600MHz, CDCl3) δ7.81-7.78(m,2H),7.73-7.70(m,4H),7.17(d,J=7.8Hz,2H),5.37(dd,J1=11.4,J2=1.8Hz,1H),4.30(dd,J1=15.6,J2=11.4Hz, 1H),3.96(dd,J1=15.0,J2=2.4Hz,1H),3.72(s,3H),2.46(t,J=7.8Hz,1H) ,1.48-1.41(m,2H),1.31(m,2H),1.27-1.21(m,3H),0.88(t,J=7.2Hz,3H); 13 CNMR (150MHz, CDCl3) δ167.36,166.93,150.08,135.71,134.44,131.64,129.30,128.26,123 .76,53.79,52.98,47.14,35.88,31.50,30.72,22.55,14.08ppm; HRMS-ESI(m / z)calcdfor[C 23 H 25 NNaO6S] + ,466.1295;found,466.1298.

[0102] In addition, the obtained compound D 1 HNMR Figure 8 As shown, 13 C NMR Fig. 9 shown.

[0103] Example 5

[0104] In the embodiment of the present invention, the specific structural formula of the sulfonylalanine (also referred to as compound E) is:

[0105] The specific preparation method of compound E is as follows:

[0106] In a glove box, dehydroalanine (44.6 mg, 0.2 mmol, 1 equiv.), 1-naphthalenesulfonyl chloride (113.3 mg, 0.5 mmol, 2.5 equiv.), tris(trimethylsilyl)silane (99.5 mg, 0.2 mmol, 2 equiv.) and acetonitrile (1.2 mL) were added to a dry round-bottom flask, and then a photocatalyst [Ru(bpz)3][PF6]2 (1.7 mg, 1% mol) was added. The mixture was reacted at room temperature (25°C) for 6 hours under irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 4:1 to 3:1) as the eluent, to finally obtain compound A as a white solid with a calculated yield of 73% and a purity of 97%.

[0107] Example 6

[0108] In the embodiment of the present invention, the specific structural formula of the sulfonylalanine (also referred to as compound F) is:

[0109] The specific preparation method of compound F is as follows:

[0110] In a glove box, dehydroalanine (44.6 mg, 0.2 mmol, 1 equiv.), coumarin-6-sulfonyl chloride (122.3 mg, 0.5 mmol, 2.5 equiv.), tris(trimethylsilyl)silane (99.5 mg, 0.2 mmol, 2 equiv.) and acetonitrile (1.2 mL) were added to a dry round-bottom flask, and then a photocatalyst [Ru(bpz)3][PF6]2 (1.7 mg, 1% mol) was added. The mixture was reacted at room temperature (25°C) for 6 hours under irradiation of blue light (100 W, 470 nm) (TLC was used as a reaction monitoring method); after the reaction was completed, the organic solvent was concentrated by rotary evaporation, and then separated and purified by silica gel column chromatography, using petroleum ether / ethyl acetate (volume ratio of 2:1 to 1:1) as the eluent, to finally obtain compound F as a white solid with a calculated yield of 63% and a purity of 98%.

[0111] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be covered by the scope of the claims of the present invention.

Claims

1. A method for preparing sulfonylalanine, characterized in that: include: The sulfonyl-containing free radical compound, a hydrogen atom donor and dehydroalanine are mixed for reaction to obtain the sulfonyl-containing alanine.

2. The preparation method according to claim 1, characterized in that: The structural formula of sulfonylalanine is R is selected from an aromatic group or a first alkyl group.

3. The preparation method according to claim 2, characterized in that: The aromatic group comprises a substituted or unsubstituted aromatic hydrocarbon group and / or a substituted or unsubstituted aromatic heterocyclic group; or The first alkyl group comprises a linear alkyl group or a cyclic alkyl group.

4. The preparation method according to claim 3, characterized in that: In aromatic groups: The aromatic hydrocarbon group is phenyl, biphenyl, triphenyl, naphthyl, binaphthyl, anthracenyl or phenanthryl; and / or the aromatic heterocyclic group is furanyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, coumarin, carbazolyl, phenanthridinyl, phenazinyl, phenoxazinyl or phenothiazinyl; in the first alkyl group: The number of carbon atoms in a straight chain alkyl group is ≤ 10; or the number of ring atoms in a cycloalkyl group is ≤ 6.

5. The preparation method according to claim 4, characterized in that: In aromatic groups: The substituents of the substituted aromatic hydrocarbon group or the substituted aromatic heterocyclic group are independently selected from one or more of a second alkyl group, a halogen group, a carboxyl group, an alkoxy group, a cyano group, a nitro group, a carbonyl group, a hydroxyl group or an amino group; In the first alkyl group: The straight chain alkyl group is n-pentyl; or the cycloalkyl group is cyclopropyl.

6. The preparation method according to claim 5, characterized in that: The second alkyl group is a linear alkyl group or a cycloalkyl group; or the halogen group is selected from fluorine, chlorine or bromine.

7. The preparation method according to claim 6, characterized in that: In the second alkyl group, the carbon number of the straight-chain alkyl group is ≤10; or the ring atom number of the cycloalkyl group is ≤6.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The sulfonyl radical-containing compound is obtained by catalysis of a sulfonyl chloride group-containing compound; and / or The hydrogen atom donor is tris(trimethylsilyl)silane; and / or The preparation method of dehydroalanine comprises: mixing phthalimide and triphenylphosphine in a solvent, and adding methyl propionate dropwise at 0-4°C to obtain dehydroalanine.

9. The preparation method according to claim 8, characterized in that: The compound containing the sulfonyl chloride group is R-SO2-Cl.

10. The preparation method according to claim 9, characterized in that: The catalytic conditions include: catalysis using a catalyst under light conditions.

11. The preparation method according to claim 10, characterized in that: The catalyst is a ruthenium-containing catalyst, Ir(ppy)3 or 4CzIPN.

12. The preparation method according to claim 11, characterized in that: The catalyst is [Ru(bpz)3][PF6]2 or Ru(bpy)3(Cl)2·6H2O.

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