A method for preparing a chiral camphorsulfonamide-modified oxacalix[4]arene

Abstract

The application belongs to the field of supramolecular chiral calixarene, and particularly relates to a preparation method of chiral camphor sulfonamide modified oxacalix[4]arene, which comprises the following steps: step one, preparation of chiral camphor sulfonamide modified oxacalix[4]arene; and step two, host-guest property research of chiral camphor sulfonamide modified oxacalix[4]arene. The application first prepares tetranitro oxacalix[4]arene through an aromatic nucleophilic substitution reaction, reduces nitro groups into amino groups, introduces camphor sulfonyl chloride derivative modules, and realizes preparation of chiral tetra-camphor sulfonamide derived oxacalix[4]arene through acylation reaction. The introduction of camphor sulfonamide enables it to simultaneously act as a hydrogen bond donor and a hydrogen bond acceptor, forms hydrogen bonds with guest molecules respectively, and occurs intermolecular interaction, and the synergistic effect of multiple sulfonamide groups can further expand and enhance the interaction force between the oxacalix[4]arene host and the guest molecules.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of supramolecular chiral calixarenes, and particularly relates to a preparation method of a chiral camphor sulfonamide modified oxacalix[4]arene. BACKGROUND

[0002] Oxacalixarene refers to a compound containing a calix[4]arene structure in a molecule, wherein the bridging carbon atoms are replaced by oxygen atoms. The molecular structure of the oxacalixarene is similar to that of the traditional calixarene, and both have a concave and convex cup-shaped structure, but the presence of oxygen atoms in the structure makes it have more diverse and rich chemical properties and reaction characteristics. Oxacalixarene has broad application prospects in host-guest inclusion, molecular recognition, supramolecular self-assembly and the like. By introducing a chiral camphor sulfonamide group, a chiral oxacalixarene molecule can be conveniently prepared for chiral recognition. Chirality is one of the basic properties of nature and plays an important role in the life process. Prolinol is an important chemical raw material intermediate, and there are two enantiomeric configurations of S(-)-prolinol and R(+)-prolinol, and the two have obvious differences in physiological activity, use and molecular recognition.

[0003] Therefore, it is of great significance to carry out research on the preparation of new chiral oxacalixarene and the host-guest recognition of chiral prolinol. SUMMARY

[0004] To solve the above technical problems, the application provides a preparation method of a chiral camphor sulfonamide modified oxacalix[4]arene, which is based on a tetraamino oxacalix[4]arene skeleton, and then a chiral enantiomer with a sulfonamide functional group is synthesized through an affinity substitution reaction of chiral camphor sulfonyl chloride and an amino group, and a chiral molecular recognition process is realized based on this.

[0005] To achieve the above technical purposes, the technical scheme adopted by the application is as follows:

[0006] A preparation method of a chiral camphor sulfonamide modified oxacalix[4]arene, characterized by comprising the following steps:

[0007] Step one, synthesis of tetranitro oxacalix[4]arene (compound 1): a mixture of 4,6-dihydroxyisophthalic acid, 1,5-difluoro-2,4-dinitrobenzene and potassium carbonate is stirred vigorously at room temperature in DMSO overnight, TLC is used to monitor the complete reaction of the raw material, ethyl acetate and a large amount of water are added to the reaction liquid, the mixture is transferred into a separatory funnel for extraction, the organic phases are combined and washed twice with saturated brine, the organic phase is collected again, dried with anhydrous Na2SO4, and rotary evaporation under reduced pressure to obtain a crude product, which is recrystallized to obtain white floccules, which are tetranitro oxacalix[4]arene;

[0008] Step two, synthesis of tetraamino calix[4]arene (compound 2): compound tetranitro calix[4]arene was dissolved in a mixed solvent of dichloromethane and methanol, and Pd / C was added as a catalyst, then hydrogen was continuously introduced into the reaction solution, and the reaction was tracked by TLC plate. After the reaction was completed, the catalyst was removed by filtration, and the filtrate was rotary evaporated to dryness. The solid was washed with methanol to obtain the pure product.

[0009] Step three, synthesis of dextrorotatory camphorsulfonamide modified calix[4]arene (compound 3): tetraamino calix[4]arene and dextrorotatory camphorsulfonyl chloride were dissolved in dichloromethane solution. The reaction was stirred at room temperature under the condition of triethylamine, and the reaction was tracked by TLC plate until the reaction was completed. The reaction was quenched by adding water, and the organic layer was washed with water for 2-5 times, saturated brine for 2-5 times, and then dried over anhydrous Na2SO4. The organic phase was filtered and rotary evaporated under reduced pressure to obtain the crude product, which was recrystallized to obtain white crystalline material, which was dextrorotatory camphorsulfonyl modified calix[4]arene.

[0010] Step four, synthesis of levorotatory camphorsulfonamide modified calix[4]arene (compound 4): tetraamino calix[4]arene and levorotatory camphorsulfonyl chloride were dissolved in dry dichloromethane solution. The reaction was stirred at room temperature under the condition of triethylamine, and the reaction was tracked by TLC plate until the reaction was completed. The reaction was quenched by adding water, and the organic layer was washed with water for 2-5 times, saturated brine for 2-5 times, and then dried over anhydrous Na2SO4. The organic phase was filtered and rotary evaporated under reduced pressure to obtain the crude product, which was recrystallized to obtain white crystalline material, which was levorotatory camphorsulfonyl modified calix[4]arene.

[0011] As a preferred, the molar ratio of compound 4,6-dihydroxyisophthalic acid, 1,5-difluoro-2,4-dinitrobenzene and potassium carbonate in step one is 1:1:2-3.

[0012] As a preferred, the volume ratio of dichloromethane: methanol in step two is 1:1-3, and the molar ratio of tetranitro calix[4]arene to Pd / C is 1:0.05-0.2.

[0013] Specifically, the molar ratio of tetraamino calix[4]arene to triethylamine in step three is 1:5-20, dichloromethane is dry dichloromethane, the stirring temperature is 20°C, and the reaction time is 6-8h.

[0014] As a preferred, the recrystallization solvent in step three is methanol.

[0015] Further, the molar ratio of tetraamino calix[4]arene to levorotatory camphorsulfonyl chloride in step four is 1:5-20.

[0016] As preferred, the molar ratio of tetraaminooxacalix[4]arene to triethylamine in the step four is 1:5-20, dichloromethane is dry dichloromethane, the stirring temperature is 20℃, and the reaction time is 6-8h. As preferred, the recrystallization solvent in the step four is a methanol solvent.

[0017] An application of the chiral camphorsulfonamide-modified oxacalix[4]arene supramolecule, which can realize the recognition of guests, especially the recognition of two enantiomers of L-prolinol (S-G1) and D-prolinol (R-G1).

[0018] Compared with the prior art, the present application has the following beneficial effects:

[0019] 1. The present application introduces camphorsulfonyl chloride as a derivative module based on the skeleton of tetraaminooxacalix[4]arene, and realizes the synthesis of tetra-camphorsulfonamide-derivatized oxacalix[4]arene through one-step nucleophilic substitution reaction.

[0020] 2. The present application acts as a hydrogen bond donor and acceptor, the N-H bond in the sulfonamide can act as a hydrogen bond donor, and the oxygen atom and the nitrogen atom can act as hydrogen bond acceptors, respectively forming hydrogen bonds with other molecules or functional groups to occur intermolecular interaction; the hydrogen bond interaction can regulate the stereochemistry of the molecules by providing or accepting hydrogen bonds in the reaction; in addition, the synergistic effect of multiple sulfonamide groups can further expand and enhance the force between the oxacalixarene host and the guest molecules. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 Chemical synthesis reaction of chiral camphorsulfonamide-modified oxacalix[4]arene;

[0022] Figure 2 1H NMR spectrum of tetraaminooxacalix[4]arene;

[0023] Figure 3 1H NMR spectrum of dextrorotatory camphorsulfonamide-modified oxacalix[4]arene;

[0024] Figure 4 1H NMR spectrum of levorotatory camphorsulfonamide-modified oxacalix[4]arene;

[0025] Figure 5 Circular dichroism (CD) of enantiomers of chiral camphorsulfonamide-modified oxacalix[4]arene;

[0026] Figure 6 X-ray crystal structure of dextrorotatory camphorsulfonamide-modified oxacalix[4]arene;

[0027] Figure 7 Crystal parameters of dextrorotatory camphorsulfonamide-modified oxacalix[4]arene;

[0028] Figure 8 NMR spectra of the interaction of the dextro-camphorsulfonamide modified oxacalix[4]arene with S-G1 / R-G1;

[0029] Figure 9 NMR spectra of the interaction of the levorotatory-camphorsulfonamide modified oxacalix[4]arene with S-G1 / R-G1;

[0030] Figure 10 NMR spectra of the interaction of the compound 3 / compound 4 with S-G2;

[0031] Figure 11 NMR spectra of the interaction of the compound 3 / compound 4 with G3; DETAILED DESCRIPTION

[0032] The present application will be described in detail below with reference to the drawings, obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0033] EMBODIMENT

[0034] A synthesis method of a chiral camphorsulfonamide modified oxacalix[4]arene, the synthesis route is as shown in Figure 1 The specific steps are as follows:

[0035] Synthesis of tetranitro-oxacalix[4]arene: a mixture of 4,6-dihydroxyisophthalic acid (26.8 g, 86.4 mmol), 1,5-difluoro-2,4-dinitrobenzene (17.6 g, 86.4 mmol) and potassium carbonate (30.0 g, 216.0 mmol, 2.5 eq.) was stirred vigorously at room temperature in DMSO overnight. TLC monitoring showed that the raw material was completely reacted, ethyl acetate and a large amount of water were added to the reaction solution, and the mixture was transferred to a separatory funnel, and the product was dissolved in the organic phase, and the organic phase and the aqueous phase were separated. The aqueous phase was collected from the lower end, and the ethyl acetate phase was poured out from the upper end, and the aqueous phase was repeatedly extracted with ethyl acetate until the aqueous phase was free of the target product, and the combined organic phase was washed twice with saturated brine, and the organic phase was collected again, and the organic phase was dried over anhydrous Na2SO4, and the crude product was obtained by rotary evaporation under reduced pressure, and white flocculent material (32.0 g, 79%) was obtained by recrystallization, which was compound 1, tetranitro-oxacalix[4]arene.

[0036]

[0037] Synthesis of tetraamino-calix[4]arene: Compound tetranitro-calix[4]arene (10.9 g, 11.5 mmol) was dissolved in dichloromethane:methanol = 1 : 1 (v:v) 150 mL mixed solvent, then 5% Pd / C was added as catalyst, and hydrogen was continuously introduced into the reaction solution. TLC plate was used to track the reaction. Compound 1 was completely catalytically hydrogenated to compound 2 in one day. The catalyst was filtered off, and the filtrate was rotary evaporated to dryness. The solid was washed with methanol to obtain pure product tetraamino-calix[4]arene (yield 100%).

[0038]

[0039] The 1H NMR spectrum of the synthesized tetraamino-calix[4]arene is shown in Figure 2 The 1H NMR spectrum of the synthesized tetraamino-calix[4]arene is shown in

[0040] Synthesis of d-camphorsulfonamide modified calix[4]arene: Tetraamino-calix[4]arene (0.42 g, 0.5 mmol, 1 eq) and d-camphorsulfonyl chloride (1.25 g, 5.0 mmol, 10 eq) were dissolved in dry dichloromethane 150 mL solution. The reaction was stirred at room temperature under the condition of triethylamine (0.7 mL, 5 mmol, 10 eq), and the reaction was tracked by TLC plate until the reaction was completed. The reaction was quenched by adding water, and the organic layer was washed with water 3 times, saturated brine 3 times, dried over anhydrous Na2SO4, filtered, and rotary evaporated under reduced pressure to obtain the crude product. Recrystallization obtained the pure compound d-camphorsulfonamide modified calix[4]arene (compound 3) as white crystals (0.71 g, 42%).

[0041]

[0042] The 1H NMR spectrum of the synthesized tetraamino-calix[4]arene is shown in 1 The 1H NMR spectrum of the synthesized tetraamino-calix[4]arene is shown in Figure 3 The 1H NMR spectrum of the synthesized tetraamino-calix[4]arene is shown ina ), 8.20 (s, 2H, ArH b ), 7.28 (s, 2H, ArH c ), 6.90 (s, 2H, ArH d ), 4.19 (m, 8H, H l ), 3.58 (d, J = 15.24 Hz, 4H, H f ), 2.73 (d, J = 15.458 Hz, 4H, H f ), 2.42-2.33 (m, 4H, H H ), 2.20 (dt, J = 18.65, Hz, J = 3.67 Hz, H i ), 2.15-2.05 (m, 4H, H m ), 1.99 (t, J = 4.34 Hz, 4H, H g ), 1.97-1.88 (m, 4H, H H ), 1.79 (s, 2H, H g ), 1.75 (s, 2H, H g ), 1.25 (s, 8H, H j ), 0.98 (d, 24H, H n ), 1.02-0.71 (s, 24H, H k ). According to the analysis of NMR spectrum, four groups of single peaks in the proton signal with chemical shifts in the region of δ = 8.3-7 ppm correspond to the aromatic ring protons of the oxygen calix[4]arene skeleton, ArH d The chemical signal of 6.90 ppm does not have the shielding effect of the 1,3 alternate conformation reported in the oxygen calix[4]arene, and it is guessed that its conformation is not the common 1,3 alternate conformation. The NH signal appears at δ = 8.95 ppm, and the chemical signals in the high field region are complex, because the chemical environment of hydrogen protons has changed after the camphorsulfonamide modification of the oxygen calix[4]arene skeleton, but the integral area shows that the total number of protons matches the target compound. 1 H NMR spectrum assisted Figure 6 X-ray single crystal structure of compound 3 proves that the compound is a right-handed camphorsulfonamide modified oxygen calix[4]arene.

[0043] Synthesis of L-camphorsulfonamide-modified oxacalix[4]arene: Tetraaminooxacalix[4]arene (0.42 g, 0.5 mmol, 1 eq) and L-camphorsulfonyl chloride (1.25 g, 5 mmol, 10 eq) were dissolved in 150 mL of dry dichloromethane. The reaction was stirred at room temperature in the presence of triethylamine (0.7 mL, 5 mmol, 10 eq) and monitored by TLC. Water was then added to quench the reaction. The organic layer was washed three times with water and three times with saturated brine, then dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to obtain the crude product. The pure compound L-camphorsulfonamide-modified oxacalix[4]arene (Compound 4) was recrystallized as white crystals (0.89 g, 53%).

[0044]

[0045] L-camphorsulfonamide modified oxacalix[4]arene 1 H NMR spectrum Figure 4 Shown (300MHz, CDCl3, TMS, 298K, ppm): δ8.96 (s, 4H, NH), 8.28 (s, 2H, ArH a ),8.20(s,2H,ArH b ),7.28(s,2H,ArH c ),6.90(s,2H,ArH d ),4.19(m,8H,H l ),3.58(d,J=15.24Hz,4H,H f ),2.73(d,J=15.458Hz,4H,H f ),2.42-2.33(m,4H,H H ),2.20(dt,J=18.65,Hz,J=3.67Hz,H i ),2.15-2.05(m,4H,H m ),1.99(t,J=4.34Hz,4H,H g ),1.97-1.88(m,4H,H H ),1.79(s,2H,H g ),1.75(s,2H,H g ),1.25(s,8H,H j ),0.98(d,24H,H n ),1.02-0.71(s,24H,H k ) According to the analysis of the nuclear magnetic spectrum, the four groups of singlets in the proton signal with chemical shifts appearing in the region of δ = 8.3 to 7 ppm correspond to the aromatic ring protons of the oxacalix[4]arene skeleton, ArHd The chemical signal of 6.9 ppm, no 1,3-alternate conformation shielding effect reported in the oxacalix[4]arene, guess its conformation is not the common 1,3-alternate conformation. NH signal appears at δ = 8.96 ppm, the chemical signal in the high field area is more complex, because the camphor sulfonamide modified oxacalix[4]arene skeleton, the chemical environment of hydrogen proton has changed, but the integral area shows the total number of protons matches the target compound. According to 1 H NMR spectrum proved that the compound is the left-handed camphor sulfonamide modified oxacalix[4]arene. In addition, by testing the circular dichroism of compound 3 and compound 4, two mirror-symmetry response curves were obtained, indicating that compound 3 and compound 4 are enantiomers.

[0046] Molecular recognition properties of chiral camphor sulfonamide modified oxacalix[4]arene:

[0047] (1) Right-handed camphor sulfonamide modified oxacalix[4]arene molecular recognition

[0048] At room temperature, the host-guest nuclear magnetic contrast analysis interaction force in deuterated chloroform, host molecule: right-handed camphor sulfonamide modified oxacalix[4]arene (compound 3), guest molecule: L-prolinol (S-G1) and D-prolinol (R-G1), its nuclear magnetic qualitative analysis as shown in Figure 8 The nuclear magnetic spectrum of 10 mM compound 3, 10 mM S-G1 and R-G1, and 10 mM compound 3 and 10 equivalents of S-G1 / R-G1 is shown.

[0049] At room temperature, the nuclear magnetic signals of the host-guest deuterated chloroform solution show great differences with the host molecule and the guest molecule (as shown in Figure 8As shown in Figure 6, the chemical shifts of the four characteristic aromatic protons H on the host molecule have all shifted significantly, with Δδ = +0.16 ppm (Ar-Ha), -0.58 ppm (Ar-Hb), -0.67 ppm (Ar-Hc), and -0.70 ppm (Ar-Hd) compared with the guest S-G1; and Δδ = +0.14 ppm (Ar-Ha), -0.54 ppm (Ar-Hb), -0.67 ppm (Ar-Hc), and -0.61 ppm (Ar-Hd) compared with the guest R-G1. This is probably because the complexation of the guest molecules with the host molecule changes the spatial configuration of the host molecule, causing it to flip from the original chair conformation to the 1,3-alternate conformation, and Ar-Ha-d is just in the shielding zone of the adjacent benzene ring. In addition, the proton Hl on the isobutyl ester group on the host molecule has changed from a multiplet to a doublet, with Δδ = -0.15 ppm (Hl); and the H2 and H3 on the guest molecules have also shifted, with Δδ = +0.02 ppm (H2) and +0.03 ppm (H3) for the guest S-G1; and Δδ = +0.02 ppm (H2) and +0.04 ppm (H3) for the guest R-G1, indicating that hydrogen bonding has been formed between the host and the guest, and host-guest complexes have been formed between the host molecule compound 3 and the guests S-G1 and R-G1, respectively.

[0050] (2) L-camphorsulfonamide-modified oxacalix[4]arene molecular recognition

[0051] NMR analysis of the host molecule L-camphorsulfonamide-modified oxacalix[4]arene (compound 4) and the guest molecules S-G1 and R-G1. The host-guest NMR comparison was performed in deuterated chloroform at room temperature. Figure 9 The NMR spectra of 10 mM compound 4, 10 mM S-G1 and R-G1, and 10 mM compound 4 with 10 equivalents of S-G1 / R-G1.

[0052] Similarly, the NMR signals in the host-guest deuterated chloroform solution at room temperature showed significant differences from both the host molecule and the guest molecule (as shown in Figure 6). Figure 9 As shown in Figure 6, the chemical shifts of the four characteristic aromatic protons H on the host molecule have all shifted significantly.

[0053] Compared with guest S-G1, Δδ = +0.16ppm (Ar-Ha), -0.59ppm (Ar-Hb), -0.69ppm (Ar-Hc), -0.68ppm (Ar-Hd); compared with guest R-G1, Δδ = +0.14ppm (Ar-Ha), -0.48ppm (Ar-Hb), -0.63ppm (Ar-Hc), -0.59ppm (Ar-Hd); this is probably because the complexation of the guest molecule with the host molecule changes the spatial configuration of the host molecule, which flips from the original chair conformation to the 1,3 alternate conformation of the oxacalix[4]arene, and Ar-Ha-d is just in the shielding area of the adjacent benzene ring. In addition, the proton Hl on the isobutyl ester group on the host changes from a multiplet to a doublet, and after complexation with S-G1, Δδ = -0.15ppm (Hl); after complexation with R-G1, Δδ = -0.13ppm (Hl). This indicates that the chemical environment may have changed; H2 and H3 on the guest molecule also have displacement changes, compared with S-G1, Δδ = +0.01ppm (H2), +0.03ppm (H3); compared with R-G1, Δδ = +0.01ppm (H2), +0.03 (H3). This indicates that hydrogen bonding is formed between the host and the guest, and host molecule compound 4 forms a host-guest complex with guest S-G1 and R-G1, respectively.

[0054] (3) Left-handed / right-handed camphor sulfonamide modified oxacalix[4]arene molecular recognition

[0055] NMR qualitative analysis of host molecule compound 3 and compound 4 and guest molecule L-pyroglutamic acid methyl ester (S-G2). At room temperature, the host-guest NMR contrast was performed in deuterated chloroform. Figure 10 The NMR spectra of 10mM S-G2, 10mM compound 3, 10mM compound 4, and 10mM compound 3 / compound 4 with an equivalent amount of S-G2.

[0056] At room temperature, the NMR signals in the host-guest deuterated chloroform solution are very different from those of the host molecule and the guest molecule (such as Figure 10NH1) of 0.04 ppm, -0.04 ppm, and -0.37 ppm, respectively, indicating that hydrogen bonding between compound 4 and S-G2 host-guest complex was formed. In summary, host molecules compound 3 and compound 4 formed host-guest complexes with S-G2, respectively.

[0057] NMR analysis of host molecules compound 3 and compound 4 with guest molecule methyl-β-D-ribofuranoside (G3). The host-guest NMR comparison was performed at room temperature in deuterated chloroform. Figure 11 The NMR spectra of 10 mM G3, 10 mM compound 3, 10 mM compound 4, and 10 mM compound 3 / compound 4 with an equivalent amount of G3.

[0058] At room temperature, the NMR signals of the host-guest deuterated chloroform solution were significantly different from those of the host molecule and the guest molecule (e.g. Figure 11 As shown, Ar-Hc of the host shifted to high field, and NH1of the guest also shifted to high field. Compound 3 with G3, compared with compound 3 and G3 alone, Δδ = -0.02 ppm (NHe), -0.04 ppm (Ar-Hc), and -0.02 ppm (H4).

[0059] This can be the result of the complex formation between compound 3 and G3. Moreover, guest proton H 4 was re-split into a t peak from the original q peak. Proton H 5 was re-split into a dd peak from the original tt peak. This can be because the chemical environment of H 4 and H 5 was changed. Compound 4 with G3, compared with compound 4 and G3 alone, Δδ = -0.02 ppm (NH e ), -0.04 ppm (Ar-H c ), and -0.02 ppm (H 4 ). This can be the result of the complex formation between compound 4 and G3. Moreover, guest proton H 4 and H 5The peak shape of compound 3 has no obvious change compared with compound 3 and G3, which indicates that the action sites between compound 3 and compound 4 and G3 are different, and that the host molecule compound 3 and compound 4 have different host-guest recognition modes and complex characteristics with the five-membered ring furanose.

Claims

1. A method for preparing chiral camphorsulfonamide-modified oxacalix[4]arene, comprising the following steps: Step 1, synthesis of tetranitrooxacalix[4]arene compound 1: a mixture of compound 4,6-dihydroxyisophthalic acid, 1,5-difluoro-2,4-dinitrobenzene and potassium carbonate was vigorously stirred in DMSO at room temperature for more than 12 hours; TLC monitored the complete reaction of the raw materials, ethyl acetate and water were added to the reaction solution, and the mixture was transferred to a separatory funnel for extraction, the organic phases were combined and washed with saturated brine 2 to 5 times, the organic phases were collected again, the organic phases were dried over anhydrous Na2SO4, and the crude product was obtained by rotary evaporation under reduced pressure, and then recrystallized to obtain a white flocculent substance, which is tetranitrooxacalix[4]arene; Step 2, synthesis of tetraaminooxacalix[4]arene compound 2: Compound 1 is dissolved in a mixed solvent of dichloromethane and methanol, and Pd / C is added as a catalyst. Then, hydrogen is continuously introduced into the reaction solution, and the reaction is tracked by TLC plate. After the reaction is completed, the catalyst is removed by filtration, the filtrate is dried, and the solid is washed with methanol to obtain a pure product, i.e., tetraaminooxacalix[4]arene; Step 3. Synthesis of right-rotating camphorsulfonamide-modified oxacalix[4]arene compound 3: Compound 2 and right-rotating camphorsulfonyl chloride were dissolved in dichloromethane solution, stirred at room temperature under the condition of triethylamine, and the reaction was tracked by TLC plate until the reaction was completed; water was then added to quench the reaction, the organic layer was washed with water 2 to 5 times, and with saturated brine 2 to 5 times, and then the organic phase was dried over anhydrous Na2SO4, filtered, and vacuum evaporated to obtain a crude product, which was recrystallized to obtain a white crystalline substance, namely right-rotating camphorsulfonamide-modified oxacalix[4]arene; Step 4. Synthesis of L-camphorsulfonamide-modified oxacalix[4]arene compound 4: Compound 2 and L-camphorsulfonyl chloride were dissolved in dry dichloromethane solution, stirred at room temperature under the condition of triethylamine, and the reaction was tracked by TLC plate until the reaction was completed; water was then added to quench the reaction, and the organic layer was washed with water 2 to 5 times, and washed with saturated brine 2 to 5 times, and then the organic phase was dried over anhydrous Na2SO4, filtered, and vacuum evaporated to obtain a crude product, which was recrystallized to obtain a white crystalline substance, namely L-camphorsulfonamide-modified oxacalix[4]arene.

2. The preparation method according to claim 1, wherein The molar ratio of the compound 4,6-dihydroxyisophthalic acid, 1,5-difluoro-2,4-dinitrobenzene and potassium carbonate in step 1 is 1:1:2-3.

3. The preparation method according to claim 1, wherein In the step 2, the volume ratio of dichloromethane to methanol is 1:1-3, and the molar ratio of tetranitrooxacalix[4]arene to Pd / C is 1:0.05-0.

2.

4. The preparation method according to claim 1, wherein The molar ratio of tetraaminooxacalix[4]arene to right-rotating camphorsulfonyl chloride in step 3 is 1:5-20.

5. The preparation method according to claim 1, wherein In the steps 3 and 4, the molar ratio of tetraaminooxacalix[4]arene to triethylamine is 1:5-20, the dichloromethane is dry dichloromethane, the stirring temperature is 20° C., and the reaction time is 6-8 h.

6. The preparation method according to claim 1, wherein The recrystallization solvent in steps 3 and 4 is methanol.

7. The preparation method according to claim 1, wherein In the step 4, the molar ratio of tetraaminooxacalix[4]arene to L-camphorsulfonyl chloride is 1:5-20.

8. Use of chiral camphorsulfonamide-modified oxacalix[4]arene prepared by the method for preparing chiral camphorsulfonamide-modified oxacalix[4]arene according to any one of claims 1 to 7, characterized in that: The chiral camphorsulfonamide-modified oxacalix[4]arene can realize the recognition of the two enantiomers of L-prolinol S-G1 and D-prolinol R-G1.

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