A series of chiral supramolecular macrocycles based on binaphthol motifs and their preparation methods and applications

Abstract

This invention discloses a series of chiral supramolecular macrocycles based on the binaphthol motif, as well as their preparation and applications. This method utilizes chiral 1,1′-bi-2,2′-naphthol (BINOL) as a reactant monomer and a transition metal reagent, Ni(cod)2, as a catalyst to synthesize these supramolecular macrocycles in high yields via a Yamamoto coupling reaction. The macrocycles can then be further hydrolyzed to yield water-soluble macrocycles in high yields. The method offers advantages such as readily available substrates, efficient and convenient reaction conditions, and the elimination of the need for further chiral resolution of the target macrocyclic product. The resulting water-soluble macrocycles exhibit high affinity for achiral molecules and high enantioselectivity for chiral molecules, demonstrating their potential for detection and identification. Fourteen steroid compounds were distinguished using fluorescence array sensing. The fluorescence array exhibits high sensitivity, lacks the need for a reference system, produces rich output signals, and is capable of imaging.

Description

Technical Field

[0001] The present invention relates to the fields of chirality and supramolecular chemistry, and in particular to a preparation method of a series of novel chiral supramolecular host macrocycles and their application in recognition and differentiation of chiral enantiomers. Background Art

[0002] Chiral recognition is widely present in nature and is a fundamental mode by which biomolecules regulate physiological functions through stereospecific substrate recognition. The development of chiral recognition receptors with high selectivity and sensitivity plays an important role in fields such as drug analysis, disease diagnosis, and food science (Liu, Y.; Wu, Z.; Armstrong, DW; Wolosker, H.; Zheng, Y. Detection and analysis of chiral molecules as disease biomarkers. Nat. Rev. Chem. 2023, 7 , 355–373), and is also a key topic in supramolecular chemistry. Macrocycles are one of the key structural building blocks of supramolecular chemistry. Their unique pre-organized cavities can coordinate multiple non-covalent interactions, making them a primary tool for effectively recognizing specific objects. By fine-tuning the chiral microenvironment, macrocycles with chiral cavities can be constructed (Jiao, J.; Dong, J.; Li, Y.; Cui, Y. Fine-tuning of chiral microenvironments within triple-stranded helicates for enhanced enantioselectivity). Angew. Chem. Int. Ed. 2021, 60 , 16568–16575) to further realize chiral recognition capabilities. It is well known that molecular recognition in life activities is mainly based on the aqueous phase. Studying the chiral recognition of macrocyclic receptors in the aqueous phase not only helps to understand the chiral recognition behavior in complex biological systems, but also provides new strategies and methods for enantioselective recognition, sensing and separation (Han, X.-N.; Li, P.-F.; Han, Y.; Chen, C.-F. Enantiomeric water-soluble octopus[3]arenes for highly enantioselective recognition of chiral ammonium salts in water. Angew. Chem. Int. Ed. 2022, 61,e202202527.). Although supramolecular chemists have made significant progress in designing a large number of new chiral macrocyclic hosts, the chiral recognition of artificially synthesized receptors in water is still difficult: first, the enantiomeric selectivity is low (generally <3) and the binding strength is not high (<10 6 M −1 ), which limits their potential applications in sensing and detecting trace chiral substrates in biological fluids, food or sewage. Secondly, the construction of new chiral macrocycles usually requires expensive chiral column separation, which poses challenges to scalability and practical implementation. Therefore, the development of chiral macrocycles with excellent enantioselectivity, high affinity and ease of synthesis remains a major challenge in the field of supramolecular chemistry. The advantages of the present invention are: the macrocycle is easy to synthesize, with high yield, easy modification, asymmetric luminescence properties, high affinity or high enantioselectivity for a variety of achiral or chiral guests, and has broad application prospects in the sensing and monitoring of steroid compounds. Summary of the Invention

[0003] The present invention provides a series of novel chiral macrocyclic molecules based on binaphthol motifs, which solve the problems of complex synthesis, generally weak binding, and low enantioselectivity of chiral macrocycles in the supramolecular field, thereby enabling efficient and economical synthesis of chiral macrocycles, molecular recognition and sensing detection.

[0004] The obtained water-soluble macrocyclic molecule has high affinity recognition for achiral molecules and high enantioselectivity for chiral molecules. The fluorescence array sensing detection of steroid compounds was used to distinguish 14 steroid compounds.

[0005] The present invention addresses the problems of complex chiral macrocycle synthesis routes, low yields, the need for expensive chiral HPLC resolution in most cases, and generally low enantioselectivity and affinity. This method provides a simple and efficient method for synthesizing chiral macrocycles. A series of chiral macrocycles are synthesized in high yields through a one-pot Yamamoto coupling reaction using chiral 1,1′-bi-2,2′-naphthol (BINOL) as a reactant monomer and a transition metal reagent Ni(cod)2 as a catalyst. These multimeric supramolecular macrocycles can be further hydrolyzed to obtain water-soluble supramolecular macrocycles. These water-soluble chiral macrocycles exhibit high affinity for molecules such as adamantane (G2, commercially available) and flavonoids (G8, commercially available), high enantioselectivity for molecules such as SPINOL (commercially available), and can distinguish 14 steroid compounds using fluorescence sensing.

[0006] The present invention simultaneously protects a series of preparation methods of chiral macrocyclic molecules based on binaphthol motifs.

[0007] The present invention simultaneously protects a series of preparation methods of chiral macrocyclic molecules based on binaphthol motifs and their applications in recognition and detection of chiral and achiral molecules.

[0008] The technical contents disclosed in the present invention are as follows:

[0009] A series of chiral supramolecular macrocycles based on the binaphthol motif have the following general structural formula:

[0010]

[0011] in:

[0012] 【1】 When the structural formula The three-dimensional conformation of the part is When, and

[0013] (1) n = 2, R' = CH2OCH3: macrocyclic RR -1

[0014] (2) n = 3, R' = CH2OCH3: macrocyclic RRR -1

[0015] (3) n = 3, R' = CH2COOCH2CH3: macrocyclic RRR -2

[0016] (4) n = 4, R' = CH2OCH3: macrocyclic RRRR -1

[0017] (5) n = 4, R' = CH2COOCH2CH3: macrocyclic RRRR -2

[0018] (6) n = 4, R' = CH2COONa: macrocyclic RRRR -3

[0019] (7) n = 4, R' = CH2COOH: macrocyclic RRRR -4

[0020] 【2】 When the structural formula The three-dimensional conformation of the part is When, and

[0021] (1) n = 2, R' = CH2OCH3: macrocyclic SS -1

[0022] (2) n = 3, R' = CH2OCH3: macrocyclic SSS -1

[0023] (3) n = 3, R' = CH2COOCH2CH3: macrocyclicSSS- 2

[0024] (4) n = 4, R' = CH2OCH3: macrocyclic SSSS -1

[0025] (5) n = 4, R' = CH2COOCH2CH3: macrocyclic SSSS -2

[0026] (6) n = 4, R' = CH2COONa: macrocyclic SSSS -3

[0027] (7) n = 4, R' = CH2COOH: macrocyclic SSSS -4

[0028] The present invention further discloses a series of chiral supramolecular macrocycles based on binaphthol motifs, wherein the macrocycle RR -1, RRR -1, RRRR -1 Its preparation method is as follows:

[0029] Ni(cod)2 (commercially available, 0.46 mmol~0.66 mmol), cod (commercially available, 0.55 mmol~0.75 mmol), 2,2'-bipyridine (commercially available, 0.48 mmol~0.68 mmol), toluene (0.2 ml~0.4 ml) and DMF (0.2 ml~0.4 ml) were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere. Then, 2 ml~4 ml of toluene dissolved in 2 ml~4 ml of dimethylbenzene was added. R -2 (0.12-0.34 mmol), and the mixture was stirred at 90 °C for 24-72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0-20 / 1 to obtain the target chiral macrocyclic compound as a white solid. RR -1, RRR -1 and RRRR -1.

[0030] A series of chiral supramolecular macrocycles SS -1, SSS -1, SSSS -1 Its preparation method is as follows:

[0031] Ni(cod)2 (commercially available, 0.46 mmol~0.66 mmol), cod (commercially available, 0.55 mmol~0.75 mmol), 2,2'-bipyridine (commercially available, 0.48 mmol~0.68 mmol), toluene (0.2 ml~0.4 ml) and DMF (0.2 ml~0.4 ml) were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere. Then, 2 ml~4 ml of toluene dissolved in 2 ml~4 ml of dimethylbenzene was added. S -2 (0.12-0.34 mmol), and the mixture was stirred at 90 °C for 24-72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0-20 / 1 to obtain the target chiral macrocyclic compound as a white solid. SS -1, SSS -1 and SSSS -1.

[0032] A series of chiral supramolecular macrocycles RRR -2 and RRRR -2 Its preparation method is as follows:

[0033] Ni(cod)2 (commercially available, 0.46 mmol~0.66 mmol), cod (commercially available, 0.55 mmol~0.75 mmol), 2,2'-bipyridine (commercially available, 0.48 mmol~0.68 mmol), toluene (0.2 ml~0.4 ml) and DMF (0.2 ml~0.4 ml) were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere. Then, 2 ml~4 ml of toluene dissolved in 2 ml~4 ml of dimethylbenzene was added. R -3 (0.12-0.34 mmol), and the mixture was stirred at 90 °C for 24-72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0-20 / 1 to obtain the target chiral macrocyclic compound as a white solid. RRR -2 and RRRR -2.

[0034] A series of chiral supramolecular macrocycles SSS -2 and SSSS -2 Its preparation method is as follows:

[0035] Ni(cod)2 (commercially available, 0.46 mmol~0.66 mmol), cod (commercially available, 0.55 mmol~0.75 mmol), 2,2'-bipyridine (commercially available, 0.48 mmol~0.68 mmol), toluene (0.2 ml~0.4 ml) and DMF (0.2 ml~0.4 ml) were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere. Then, 2 ml~4 ml of toluene dissolved in 2 ml~4 ml of dimethylbenzene was added. S -3 (0.12-0.34 mmol), and the mixture was stirred at 90 °C for 24-72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0 to 20 / 1 to obtain the target chiral macrocyclic compound as a white solid. SSS -2 and SSSS -2.

[0036] Chiral supramolecular macrocycle RRRR -3 and RRRR -4 Its preparation method is as follows:

[0037] Will RRRR A mixture of -2 (0.027 mmol), 20% aqueous NaOH (1 ml to 2 ml), THF (1 ml to 2 ml), and CH3OH (1 ml to 2 ml) was stirred at 90 °C for 12 h to 24 h. The mixture was evaporated under reduced pressure. The crude product was purified by spherical C18 silica gel column chromatography (H2O to H2O / CH3CN = 10 / 1) to obtain the target compound as a white solid. RRRR -3. 100mg RRRR -3 solid was dissolved in water, 10~20 ml of 1M hydrochloric acid was added, and after stirring for 10~20 min, the precipitated white precipitate was filtered and washed with 10~20 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. RRRR -4.

[0038] Chiral supramolecular macrocycle SSSS -3 and SSSS -4, its synthesis steps are as follows:

[0039] Will SSSSA mixture of -2 (0.027 mmol), 20% aqueous NaOH (1 ml to 2 ml), THF (1 ml to 2 ml), and CH3OH (1 ml to 2 ml) was stirred at 90 °C for 12 h to 24 h. The mixture was evaporated under reduced pressure. The crude product was purified by spherical C18 silica gel column chromatography (H2O to H2O / CH3CN = 10 / 1) to obtain the target compound as a white solid. SSSS -3, 100mg SSSS -3 solid was dissolved in water, 10~20 ml of 1M hydrochloric acid was added, and after stirring for 10~20 min, the precipitated white precipitate was filtered and washed with 10~20 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. SSSS -4.

[0040] The synthesis steps are as follows:

[0041]

[0042]

[0043] in R -1 synthesis reference (Y. Nojima, M. Hasegawa, N. Hara, Y. Imai, Y.Mazaki, Chem. Commun. 2019, 55, 2749–2752)

[0044] The present invention further discloses the application of a series of chiral supramolecular macrocycles based on the binaphthol motif for the identification of chiral and achiral molecules. Experimental results demonstrate that the identification of chiral and achiral molecules can be used for detection applications. In particular, fluorescence array sensing can be used for the identification and sensing of steroids, enabling the differentiation of 14 steroid compounds.

[0045] The present invention simultaneously protects a series of preparation methods of novel chiral macrocyclic molecules based on binaphthol motifs and their applications in steroid sensing.

[0046] The working principle of this invention is that the synthesized water-soluble chiral macrocycle has non-covalent interactions with the guest, such as hydrophobic and electrostatic interactions, which endow the macrocycle with high affinity for many achiral guests (such as adamantane and flavonoids) and high enantioselectivity for specific chiral guests (such as SPINOL), thereby enabling the identification and detection of specific compounds. In addition, the fluorescence array sensor can achieve the distinction of 14 steroid compounds.

[0047] A series of chiral macrocycles based on the BINOL skeleton have the following structures:

[0048]

[0049] A. A series of novel chiral macrocycles based on the BINOL skeleton RR -1, RRR -1 and RRRR -1, the synthesis method is as follows:

[0050] (1) Compound R A mixture of -1 (1 g) and THF (30 mL) was stirred at 0°C for 10 min. NaH (commercially available) was added to the mixture and stirring continued at 0°C for 10 min. Bromomethyl methyl ether (commercially available) was added to the mixture and the mixture was allowed to react at room temperature for 12 hours. Extraction was performed with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. R -2 (2.0 g, 3.2 mmol).

[0051] 1 H NMR (400 MHz, CDCl3, 298 K) of R -2: δ H = 7.93 (d, J = 9.0 Hz, 2H),7.75 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.43 (dd, J = 8.7, 2.0 Hz, 2H),7.30 (d, J = 1.9 Hz, 2H), 7.26 (s, 2H), 5.13 (d, J = 6.9 Hz, 2H), 4.99 (d, J = 7.0Hz, 2H), 3.21 (s, 6H).

[0052] (2) A Schlenk tube containing Ni(cod)2 (commercial) (384 mg, 1.4 mmol), cod (commercial) (0.2 ml, 1.63 mmol), 2,2'-bipyridine (commercial) (224 mg, 1.43 mmol), toluene (1.1 ml) and DMF (1.1 ml) was stirred at 90 °C for 30 min under N2 atmosphere. Then, Ni(cod)2 dissolved in toluene (5.4 mL) was added. R-2, and the mixture was stirred at 90 ° C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. RR -1, RRR -1 and RRRR -1

[0053] 1 H NMR (400 MHz, CDCl3, 298 K) of RR -1: δ H = 7.88 (d, J = 9.0 Hz, 4H), 7.72 (d, J = 8.2 Hz, 4H), 7.54 (d, J = 9.0 Hz, 4H), 7.23 (dd, J = 8.3, 1.5Hz, 4H), 6.95 (s, 4H), 5.07 (d, J = 6.6 Hz, 4H), 4.92 (d, J = 6.6 Hz, 4H), 3.21 (s, 12H).

[0054] 1 H NMR (400 MHz, CDCl3, 298 K) of RRR -1: δ H = 7.83 (d, J = 9.0 Hz, 6H), 7.65 (d, J = 8.4 Hz, 6H), 7.52 (d, J = 9.0 Hz, 6H), 7.10 (d, J = 8.4 Hz, 6H), 6.91 (s, 6H), 5.20 (d, J = 6.8 Hz, 6H), 4.98 (d, J = 6.8 Hz, 6H), 3.11 (s,18H).

[0055] 1 H NMR (400 MHz, CDCl3, 298 K) of RRRR -1: δ H =7.84 (d, J = 9.0 Hz, 8H), 7.65 (d, J = 8.5 Hz, 8H), 7.54 (d, J = 9.0 Hz, 8H), 7.35 (s, 8H), 7.22 (d, J = 8.9 Hz, 8H), 5.09 (d, J = 6.8 Hz, 8H), 5.01 (d, J = 6.8 Hz, 8H), 3.12(s, 24H).

[0056] B. A series of novel chiral macrocycles based on the BINOL skeleton RRR -2 and RRRR -2, the synthesis method is as follows:

[0057] (1) Compound R -1 (1.5 g, 3.4 mmol, its synthesis reference Y. Nojima, M. Hasegawa, N.Hara, Y. Imai, Y. Mazaki, Chem. Commun. 2019, 55, A mixture of 2749–2752 (2749–2752), Cs2CO3 (8.8 g, 27.2 mmol), ethyl bromoacetate (commercially available) (1.1 ml, 10 mmol), and DMF (20 mL) was stirred at 40 °C for 24 hours. Saturated NH4Cl solution was added to the mixture, extracted with CH2Cl2, and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. R -3 (2.0 g, 3.2 mmol).

[0058] 1 H NMR (400 MHz, CDCl3, 298 K) of R -3: δ H = 7.92 (d, J = 9.0 Hz, 2H),7.73 (d, J = 8.7 Hz, 2H), 7.43 (dd, J 1= 8.4 Hz, J 2= ​​1.8 Hz, 2H), δ 7.34 (s, 2H),7.32 (d, J = 9.0 Hz, 2H), 4.57 (m, 4H), 4.16 (m, 4H), 1.18 (t, J = 7.1 Hz, 6H). 13CNMR (100 MHz, CDCl3, 298 K) of R -3: δ C HR-ESI-MS: calculated for C 28 H 24 Br2NaO6([ M +Na] + ): 638.9812; found 638.9813.

[0059] (2) A Schlenk tube containing Ni(cod)2 (commercially available) (154 mg, 0.56 mmol), cod (commercially available) (70 mg, 0.65 mmol), 2,2'-bipyridine (commercially available) (90 mg, 0.58 mmol), toluene (0.3 ml) and DMF (0.3 ml) was stirred at 90 °C for 30 minutes under N2 atmosphere. Then, a solution of Ni(cod)2 dissolved in toluene (2.4 mL) was added. R -3, and the mixture was stirred at 90 ° C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. RRR -2 (23.9 mg, 0.013 mmol) and RRRR -2 (21.6 mg, 0.012 mmol)

[0060] 1 H NMR (400 MHz, CDCl3, 298 K) of RRR -2: δ H =7.82 (d, J = 9.1 Hz, 6H), 7.64 (d, J = 8.4 Hz, 6H), 7.29 (d, J = 9.2 Hz, 6H), 7.25 (d, J = 8.4 Hz, 6H), 6.95 (s, 6H), 4.62–4.51 (m, 12H), 4.14 (q, J = 7.1 Hz, 12H), 1.18 (t, J = 7.1Hz, 18H).

[0061] 1 H NMR (400 MHz, CDCl3, 298 K) of RRRR -2: δ H = 7.84 (d, J = 9.0 Hz, 8H),7.64 (d, J = 8.5 Hz, 8H), 7.37 (s, 8H), 7.31 (d, J = 8.7 Hz, 8H), 7.29 (d, J = 9.0Hz, 8H), 4.52 (dd, J 1= 18.8 Hz, J 2= ​​16.4 Hz, 16H), 4.11 (q, J = 7.1 Hz, 16H),1.14 (t, J = 7.1 Hz, 24H). 13 C NMR (100 MHz, CDCl3, 298 K) of RRRR -2: δ C HR-ESI-MS: calculated for C 112 H 96 NaO 24 ([ M +Na] + ):1848.6218; found 1848.6212.

[0062] C. New chiral macrocycles based on the BINOL skeleton RRRR -3 and RRRR -4, the synthesis method is as follows:

[0063] (1) RRRR A mixture of -2 (50 mg, 0.027 mmol), 20% aqueous NaOH (1.0 ml), THF (1.0 ml), and CH3OH (1.8 ml) was stirred at 90°C overnight. The mixture was evaporated under reduced pressure. The crude product was purified by spherical C18 silica gel column chromatography (H2O to H2O / CH3CN = 10 / 1) to obtain the title compound as a white solid. RRRR -3 (47 mg, 0.027 mmol), 100 mg solid RRRR -3 was dissolved in water, 10 ml of 1M hydrochloric acid was added, and after stirring for 10 min, the precipitated white precipitate was filtered and washed with 10 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. RRRR -4. 1 H NMR (400 MHz, CDCl3, 298 K) of RRRR -3: δ H = 8.05 (d, J = 9.2 Hz, 8H), 7.76(d, J = 8.5 Hz, 8H), 7.40 (d, J = 9.2 Hz, 8H), 7.25 (s, 8H), 7.22 (d, J = 8.5 Hz,8H), 4.50 (d, J = 16.3 Hz, 8H), 4.39 (d, J = 16.3 Hz, 8H). 13 C NMR (100 MHz, CDCl3,298 K) of RRRR -3: δ C = 176.88, 166.63, 154.32, 132.83, 129.86, 128.28, 123.58,123.11, 118.76, 115.52, 68.97, 23.30. HR-ESI-MS: calculated for C 96 H 59 NaO 24 ([ M -7Na+3H] 4+ ): 404.8337; found 404.8336.

[0064] D. A series of novel chiral macrocycles based on the BINOL skeleton SS -1,SSS -1 and SSSS -1, the synthesis method is as follows:

[0065] (1) Compound S -1 (1 g, 2.25 mmol, its synthesis reference Y. Nojima, M. Hasegawa, N.Hara, Y. Imai, Y. Mazaki, Chem. Commun. 2019, 55, A mixture of 2749–2752 mL of ethanol (2749–2752 mL) and THF (30 mL) was stirred at 0°C for 10 min. NaH was added to the mixture, and stirring was continued at 0°C for 10 min. Bromomethyl methyl ether was added to the mixture, and the reaction was allowed to react at room temperature for 12 hours. Extraction was performed with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. S -2 (2.0 g, 3.2 mmol), 1 H NMR characterization was consistent with S chirality.

[0066] (2) A Schlenk tube containing Ni(cod)2 (commercially available) (384 mg, 1.4 mmol), cod (commercially available) (0.2 ml, 1.63 mmol), 2,2'-bipyridine (commercially available) (224 mg, 1.43 mmol), toluene (1.1 ml) and DMF (1.1 ml) was stirred at 90 °C for 30 minutes under N2 atmosphere. Then, Ni(cod)2 dissolved in toluene (5.4 mL) was added. S -2, and the mixture was stirred at 90 °C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. SS -1, SSS -1 and SSSS -1.

[0067] 1 H NMR (400 MHz, CDCl3, 298 K) of SS -1: δ H =7.87 (d, J = 9.0 Hz, 4H), 7.72 (d, J = 8.3 Hz, 4H), 7.54 (d, J = 9.0 Hz, 4H), 7.23 (dd, J = 8.2, 1.6Hz, 4H), 6.95 (s, 4H), 5.07 (d, J = 6.6 Hz, 4H), 4.91 (d, J = 6.6 Hz, 4H), 3.21 (s, 12H).

[0068] 1 H NMR (400 MHz, CDCl3, 298 K) of SSS -1: δ H = 7.83 (d, J = 9.0 Hz, 6H), 7.65 (d, J = 8.4 Hz, 6H), 7.51 (d, J = 9.0 Hz, 6H), 7.10 (d, J = 8.4 Hz, 6H), 6.91 (s, 6H), 5.19 (d, J = 6.8 Hz, 6H), 4.98 (d, J = 6.8 Hz, 6H), 3.11 (s,18H).

[0069] 1 H NMR (400 MHz, CDCl3, 298 K) of SSSS -1: δ H = 7.83 (d, J = 9.0 Hz, 8H), 7.64 (d, J = 8.5 Hz, 8H), 7.54 (d, J = 9.1 Hz, 8H), 7.33 (s, 8H), 7.22 (d, J = 8.9 Hz, 8H), 5.08 (d, J = 6.7 Hz, 8H), 5.01 (d, J = 6.7 Hz, 8H), 3.12(s, 24H).

[0070] E. A series of novel chiral macrocycles based on the BINOL skeleton SSS -2 and SSSS -2, the synthesis method is as follows:

[0071] (1) Compound S -1 (1.5 g, 3.4 mmol, its synthesis reference Y. Nojima, M. Hasegawa, N.Hara, Y. Imai, Y. Mazaki, Chem. Commun.2019, 55, A mixture of 2749–2752 (2749–2752), Cs2CO3 (8.8 g, 27.2 mmol), ethyl bromoacetate (commercially available) (1.1 ml, 10 mmol), and DMF (20 mL) was stirred at 40 °C for 24 hours. Saturated NH4Cl solution was added to the mixture, extracted with CH2Cl2, and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. S -3.

[0072] 1 H NMR (400 MHz, CDCl3, 298 K) of S -3: δ H = 7.91 (d, J = 9.1 Hz, 2H),7.72 (d, J = 8.7 Hz, 2H), 7.43 (dd, J 1= 8.7 Hz, J 2=1.8 Hz, 2H), δ 7.35 (s, 2H),7.31 (d, J = 9.3 Hz, 2H), 4.56 (m, 4H), 4.16 (m, 4H), 1.17 (t, J = 7.2 Hz, 6H). 13 CNMR (100 MHz, CDCl3, 298 K) of S -3: δ C = 167.90, 153.24, 134.09, 128.91, 128.66,127.07, 126.62, 126.31, 120.37, 117.55, 114.12, 65.63, 60.16, 13.06.

[0073] (2) A Schlenk tube containing Ni(cod)2 (commercially available) (154 mg, 0.56 mmol), cod (commercially available) (70 mg, 0.65 mmol), 2,2'-bipyridine (commercially available) (90 mg, 0.58 mmol), toluene (0.3 ml) and DMF (0.3 ml) was stirred at 90 °C for 30 minutes under N2 atmosphere. Then, a solution of Ni(cod)2 dissolved in toluene (2.4 mL) was added. S-3, and the mixture was stirred at 90 ° C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. SSS -2 and SSSS -2.

[0074] 1 H NMR (400 MHz, CDCl3, 298 K) of SSS -2: δ H = 7.82 (d, J = 9.0 Hz, 6H), 7.64 (d, J = 8.5 Hz, 6H), 7.29 (d, J = 9.2 Hz, 6H), 7.25 (d, J = 8.4 Hz, 6H), 6.95 (s, 6H), 4.65–4.52 (m, 12H), 4.13 (q, J = 7.1 Hz, 12H), 1.18 (t, J = 7.1Hz, 18H).

[0075] 1 H NMR (400 MHz, CDCl3, 298 K) of SSSS -2: δ H = 7.83 (d, J = 9.1 Hz, 8H),7.62 (d, J = 8.5 Hz, 8H), 7.34 (s, 8H), 7.34 (d, J = 8.7 Hz, 8H), 7.29 (d, J = 9.0Hz, 8H), 4.51 (dd, J 1= 18.8 Hz, J 2= ​​16.4 Hz, 16H), 4.10 (q, J = 7.2 Hz, 16H), 1.05(t, J = 7.2 Hz, 24H). 13 C NMR (100 MHz, CDCl3, 298 K) of SSSS -2:: δ C= 169.31,153.84, 138.38, 133.89, 129.25, 128.93, 128.02, 123.92, 123.28, 120.47,115.28, 67.11, 60.96, 14.00.

[0076] F. New chiral macrocycles based on the BINOL skeleton [[ID=第93]]SSSS -3 and SSSS -4, the synthesis method is as follows:

[0077] (1) SSSS- A mixture of 2 (50 mg, 0.027 mmol), 20% aqueous NaOH (1.0 ml), THF (1.0 ml), and CH3OH (1.8 ml) was stirred at 90°C overnight. The mixture was evaporated under reduced pressure. The crude product was purified by spherical C18 silica gel column chromatography (H2O to H2O / CH3CN = 10 / 1) to obtain the title compound as a white solid. SSSS -3. 100 mg solid SSSS -3 was dissolved in water, 10 ml of 1M hydrochloric acid was added, and after stirring for 10 min, the precipitated white precipitate was filtered and washed with 10 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. SSSS -4. 1 H NMR (400 MHz, CDCl3, 298 K) of SSSS -3: δ H = 8.00 (d, J = 9.2 Hz, 8H), 7.73 (d, J = 8.8 Hz, 8H),7.36 (d, J = 9.2 Hz, 8H), 7.23 (s, 8H), 7.20 (d, J = 8.5 Hz, 8H), 4.47 (d, J = 14.7Hz, 8H), 4.36 (d, J = 14.7 Hz, 8H). 13 C NMR (100 MHz, CDCl3, 298 K) of -3: δ C = 176.93, 164.03, 154.21, 132.98, 129.81, 128.31, 123.52, 122.51, 118.53,115.17, 68.43, 23.20.

[0078] G. Water-soluble macrocycles SSSS 3. Recognition properties of achiral guests adamantane G2 and calendula G8:

[0079] By titrating different equivalents of the guest, tracking RRRR- Fluorescence titration experiments were performed using Origin Lab 9.1 software and a 1:1 binding model (Guo, D.-S.; Uzunova, VD; Su, X.; Liu, Y.; Nau, WM). Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions. RRRR .2011, 2 , 1722–1734) was fitted to the fluorescence intensity versus guest concentration plot to calculate the binding constant. K a. Download the fitting module from Professor Nau's group website (http: / / www.jacobs-university.de / ses / wnau) under the "Fitting Function" column. Detailed description is as follows:

[0080] i) The concentration is 0.025 μM Chem. Sci -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add G2 (see RRRR ) to 0.40 μM, and monitor the change curve of fluorescence intensity. Figure 1 As can be seen from (a), the fluorescence intensity of the mixture gradually increases. Further fitting the fluorescence intensity change of the mixture at a wavelength of 400 nm, from Figure 1 As can be seen from (b), the binding constant K a After fitting, it was determined to be (3.08±0.99)×10 8 M −1 .

[0081] ii) Match Figure 1 -3 concentration was 0.025 μM and G8 (see RRRR ) concentration was 0.020 μM Figure 1-3 and G8 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add G2 (see RRRR ) to 51.3 μM, and the change curve of fluorescence intensity was monitored. Figure 1 As can be seen from (c), the fluorescence intensity of the mixture gradually increases. Further fitting the fluorescence intensity change of the mixture at a wavelength of 400 nm, from Figure 1 As can be seen from (d), the binding constant K a After fitting, it was determined to be (8.57±0.82)×10 10 M −1 . Figure 1 (c) The inset shows the total molar concentration of 0.25 μM. Figure 1 The job plot of the fluorescence emission changes of -3 and G8 at 400 nm shows that the host-guest binding model conforms to 1:1.

[0082] H. Water-soluble macrocycles RRRR 3. Recognition properties of the chiral guest SPINOL (commercially available):

[0083] By tracking the titration of different equivalents of the guest RRRR- Fluorescence titration experiments were performed using Origin Lab 9.1 software and a 1:1 binding model (Guo, D.-S.; Uzunova, VD; Su, X.; Liu, Y.; Nau, WM). Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions. RRRR .2011, 2 , 1722–1734) was fitted to the fluorescence intensity versus guest concentration plot to calculate the binding constant. K a. Download the fitting module from Professor Nau's group website (http: / / www.jacobs-university.de / ses / wnau) under the "Fitting Function" column. Detailed description is as follows:

[0084] i) The concentration of 2.5 μM Chem. Sci-3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( S )-SPINOL to 70 μM, monitor the change curve of fluorescence intensity, and further fit the change of the mixture fluorescence intensity at a wavelength of 400 nm. SSSS As can be seen in (a), the fluorescence intensity of the mixture gradually increases. Figure 2 (b), Binding constant K a After fitting, it was determined to be (9.88±2.51)×10 4 M −1 .

[0085] ii) with a concentration of 2.5 μM Figure 2 -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( S )-SPINOL to 650 μM, monitor the change curve of fluorescence intensity, and further fit the change of the mixture fluorescence intensity at a wavelength of 400 nm. RRRR As can be seen in (c), the fluorescence intensity of the mixture gradually decreases. Figure 2 (d), binding constant K a After fitting, it was determined to be (5.26±1.13)×10 3 M −1 .

[0086] iii) with a concentration of 2.5 μM Figure 2 -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( R )-SPINOL was added to 700 μM, and the change curve of fluorescence intensity was monitored. The change of the fluorescence intensity of the mixture at a wavelength of 400 nm was further fitted. SSSS As can be seen in (e), the fluorescence intensity of the mixture gradually decreases. Figure 2 (f), binding constant K a After fitting, it was determined to be (5.34±0.91)×10 3 M −1 .

[0087] iv) with a concentration of 2.5 μM Figure 2-3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( R )-SPINOL to 45 μM, monitor the change curve of fluorescence intensity, and further fit the change of the mixture fluorescence intensity at a wavelength of 400 nm. RRRR As can be seen in (g), the fluorescence intensity of the mixture gradually decreases. Figure 2 (h), binding constant K a After fitting, it was determined to be (8.65±2.03)×10 4 M −1 .

[0088] analyze Figure 2 The data obtained can be used to conclude that water-soluble macrocyclic Figure 4 The enantioselectivity of 3 for the chiral guest SPINOL ( K S / K R or K R / K S ) reached 18.8.

[0089] I. Water-soluble macrocycles RRRR- 3. Identification properties of the steroid compound megestrol acetate:

[0090] By tracking the titration of different equivalents of the guest RRRR- Fluorescence titration experiments were performed using Origin Lab 9.1 software and a 1:1 binding model (Guo, D.-S.; Uzunova, VD; Su, X.; Liu, Y.; Nau, WM). Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions. RRRR .2011, 2 , 1722–1734) was fitted to the fluorescence intensity versus guest concentration plot to calculate the binding constant. K a. Download the fitting module from Professor Nau's group website (http: / / www.jacobs-university.de / ses / wnau) under the "Fitting Function" column. Detailed description is as follows:

[0091] i) match Chem. Sci -3 concentration was 0.025 μM and G8 concentration was 0.025 μM RRRR Take 2.5 ml of the mixture of -3 and G8 in a cuvette, excite with a wavelength of 300 nm, measure the fluorescence spectrum of the solution in the wavelength range of 350~550 nm, continuously add megestrol acetate to 75 μM, monitor the change curve of fluorescence intensity, and RRRR As can be seen from (a), the fluorescence intensity of the mixture gradually increases. Further fitting the fluorescence intensity change of the mixture at a wavelength of 400 nm, from Figure 3 As can be seen from (b), the binding constant K a After fitting, it was determined to be (4.37±0.29)×10 10 M −1 .

[0092] analyze Figure 3 The data obtained can be used to conclude that water-soluble macrocyclic Figure 3 3 has a strong recognition ability for the steroid compound megestrol acetate.

[0093] J. Water-soluble macrocycles RRRR- 3. RRRR- Array sensing of 3 pairs of 14 steroid compounds is used to distinguish steroid compounds. The specific operation is as follows.

[0094] Determination of water-soluble macrocycles SSSS- 3. RRRR- 3 pairs of 14 steroid compounds fluorescence sensor array, the sensor array consists of a series of water-soluble macrocyclic SSSS- 3. RRRR- 3 and steroid compounds of different concentrations form sensing units. The characteristic spectrum generated by each sensing unit in response to 14 steroid compounds can realize the identification and detection of specific substances. The fluorescence sensor array has the advantages of high sensitivity, no need for a reference system, rich output signals, and the ability to image. It has become the focus of sensor array development in recent years.

[0095] from SSSS- It can be seen that Figure 3 (a) Figure 3 3 can distinguish 8 steroid compounds, SSSS- (b) Figure 3 3 can distinguish 10 steroid compounds, and two chiral water-soluble macrocyclic RRRR- 3 and SSSS- 3 together achieved the distinction of 14 steroid compounds, further demonstrating the importance of chirality in the sensing of this array.

[0096] A series of new chiral macrocycles based on the BINOL skeleton are reported. RRRR- 1, RR- 1, SS- 1, RRR- 1, [[ID=第158]]SSS- 2, RRR- 2, SSS- 1, RRRR- 1, SSSS- 2, RRRR- 2, [[ID=第164]]SSSS- 3. RRRR- 3. SSSS- 4. RRRR- Synthesis method of 4: Chirally pure binaphthyl monomer R -1 and S- 1 Modification with different substituents to form cyclized precursors R -2, S- 2, R -3 and S- 3. A series of polymeric supramolecular macrocycles were synthesized in high yields through a one-pot Yamamoto coupling reaction catalyzed by a metal transition reagent Ni (cod) 2. SSSS- 1, RR- 1, SS- 1, RRR- 1, SSS- 2, RRR- 2, SSS- 1, RRRR- 1, SSSS- 2 and RRRR- 2, and can be further hydrolyzed to obtain water-soluble supramolecular macrocycles SSSS- 3 and RRRR- 3. After acidification, a macrocyclic ring with a carboxylic acid as the substituent is obtained SSSS- 4 and RRRR- 4. Characterization of chiral macrocycles by various characterization methods SSSS- 1, RR- 1, SS- 1, RRR- 1, SSS- 2, RRR- 2, SSS- 1, RRRR- 1, 2, SSSS- 2, RRRR- 3. SSSS- 3. [[ID=19〕]]RRRR- 4. SSSS- 4 structures were characterized to confirm the successful synthesis of chiral macrocycles. RRRR- 3. SSSS- 3 were further studied in water, using fluorescence titration to determine the macrocyclic RRRR- 3. SSSS-3 The binding constants of different guests were tested in water. The data showed that the water-soluble macrocyclic RRRR- 3. SSSS- 3 has a generally high binding strength to achiral guests (10 7 ~10 10 ), and has high enantioselectivity for a series of chiral objects, with the highest selectivity reaching 18.8. This is the highest binding strength and enantioselectivity of chiral macrocyclic receptors in aqueous phase. In addition, the water-soluble macrocyclic RRRR- 3. SSSS- 3. To investigate the binding strength of steroid compounds, we further used water-soluble macrocyclic RRRR- 3. SSSS- Array sensing tests were conducted on 3 pairs of steroid compounds, achieving the distinction of 14 steroid compounds in water. It is convenient, sensitive, and has commercial value. BRIEF DESCRIPTION OF THE DRAWINGS

[0097] RRRR- Fluorometric titration of macrocycles SSSS- 3 complexation of achiral guests G2 and G8; Figure 1 Fluorescence titration curve (a) and fluorescence intensity fitting curve (b) of G2 added to 3; RRRR- Fluorescence titration curve (c) and fluorescence intensity fitting curve (d) of G8 added in 3;

[0098] RRRR- Fluorometric titration of macrocycles RRRR- 3. Figure 2 3. Complexation of chiral guest SPINOL. RRRR- 3 drops S Fluorescence titration curve (a) and fluorescence intensity fitting curve (b) of -SPINOL; SSSS- 3 drops S -SPINOL fluorescence titration curve (c) and fluorescence intensity fitting curve (d); [[ID=21〕]]SSSS- 3 drops R -SPINOL fluorescence titration curve (e) and fluorescence intensity fitting curve (f); RRRR- 3 drops R -Fluorescence titration curve (g) and fluorescence intensity fitting curve (h) of SPINOL;

[0099] SSSS- Fluorometric titration of macrocycles RRRR- 3. Figure 3 3. Complexation of steroid compound - megestrol acetate; RRRR- Fluorescence titration curve (a) and fluorescence intensity fitting curve (b) of megestrol acetate added in 3;

[0100] SSSS- Water-soluble macrocyclic RRRR- 3. Figure 4 3 array sensorgrams for 14 steroid compounds; RRRR- The points in (a) are rocuronium, pancuronium, androsterone, cholesterol, bile acid, β-estradiol, estriol, prednisolone, estrone, androstenedione, testosterone, progesterone, and megestrol acetate from left to right; SSSS- The points in (b) are, from left to right, nandrolone, cholesterol, rocuronium, bile acid, androsterone, pancuronium, estriol, estrone, β-estradiol, prednisolone, progesterone, testosterone, androstenedione, and megestrol acetate. Figure 4 The points in (c) are, from left to right, nandrolone, rocuronium, cholesterol, bile acid, androsterone, pancuronium, estriol, estrone, β-estradiol, prednisolone, progesterone, testosterone, androstenedione, and megestrol acetate. Implementation Method

[0101] The present invention is described below through specific embodiments. Unless otherwise specified, the technical means used in the present invention are methods well known to those skilled in the art. In addition, the embodiments should be understood as illustrative rather than limiting the scope of the present invention, and the essence and scope of the present invention are limited only by the claims. For those skilled in the art, various changes or modifications to the material components and dosages in these embodiments, without departing from the essence and scope of the present invention, also fall within the scope of protection of the present invention. The raw materials and reagents used in the present invention are all commercially available. R -1 synthesis reference (Y.Nojima, M. Hasegawa, N. Hara, Y. Imai, Y. Mazaki, Figure 4 2019, 55, 2749–2752).

[0102] Example 1

[0103] A series of new chiral macrocycles based on the BINOL skeleton Figure 4 -1, Chem. Commun. -1 and RR -1, prepared by the following specific reaction steps:

[0104] (1) Compound RA mixture of -1 (1 g, 2.25 mmol) and THF (30 mL) was stirred at 0°C for 10 min. NaH was added to the mixture, and stirring was continued at 0°C for 10 min. Bromomethyl methyl ether was added to the mixture, and the reaction was allowed to react at room temperature for 12 hours. Extraction was performed with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. R -2 (2.0 g, 3.2 mmol).

[0105] 1 H NMR (400 MHz, CDCl3, 298 K) of R -2: δ H = 7.93 (d, J = 9.0 Hz, 2H),7.75 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.43 (dd, J = 8.7, 2.0 Hz, 2H),7.30 (d, J = 1.9 Hz, 2H), 7.26 (s, 2H), 5.13 (d, J = 6.9 Hz, 2H), 4.99 (d, J = 7.0Hz, 2H), 3.21 (s, 6H).

[0106] (2) A Schlenk tube containing Ni(cod)2 (384 mg, 1.4 mmol), cod (0.2 ml, 1.63 mmol), 2,2'-bipyridine (224 mg, 1.43 mmol), toluene (1.1 ml) and DMF (1.1 ml) was stirred at 90 °C for 30 min under N2 atmosphere. Then, Ni(cod)2 dissolved in toluene (5.4 mL) was added. R -2, and the mixture was stirred at 90 °C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. RRR -1, RRRR -1 and RR -1

[0107] 1 H NMR (400 MHz, CDCl3, 298 K) of RRR -1: δ H = 7.88 (d, J = 9.0 Hz, 4H), 7.72 (d, J = 8.2 Hz, 4H), 7.54 (d, J = 9.0 Hz, 4H), 7.23 (dd, J = 8.3, 1.5Hz, 4H), 6.95 (s, 4H), 5.07 (d, J = 6.6 Hz, 4H), 4.92 (d, J = 6.6 Hz, 4H), 3.21 (s, 12H).

[0108] 1 H NMR (400 MHz, CDCl3, 298 K) of RRRR -1: δ H = 7.83 (d, J = 9.0 Hz, 6H), 7.65 (d, J = 8.4 Hz, 6H), 7.52 (d, J = 9.0 Hz, 6H), 7.10 (d, J = 8.4 Hz, 6H), 6.91 (s, 6H), 5.20 (d, J = 6.8 Hz, 6H), 4.98 (d, J = 6.8 Hz, 6H), 3.11 (s,18H).

[0109] 1 H NMR (400 MHz, CDCl3, 298 K) of RR RRR RRRR -1: δ H = 7.84 (d, J = 9.0 Hz, 8H), 7.65 (d, J = 8.5 Hz, 8H), 7.54 (d, J = 9.0 Hz, 8H), 7.35 (s, 8H), 7.22 (d, J = 8.9 Hz, 8H), 5.09 (d, J = 6.8 Hz, 8H), 5.01 (d, J = 6.8 Hz, 8H), 3.12(s, 24H). Example

[0110] A series of new chiral macrocycles based on the BINOL skeleton RRR -2 and RRRR -2, prepared by the following specific reaction steps:

[0111] (1) Compound R A mixture of -1 (1.5 g, 3.4 mmol), Cs2CO3 (8.8 g, 27.2 mmol), ethyl bromoacetate (1.1 ml, 10 mmol), and DMF (20 mL) was stirred at 40 °C for 24 hours. Saturated NH4Cl solution was added to the mixture, extracted with CH2Cl2, and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. R -3 (2.0 g, 3.2 mmol).

[0112] 1 H NMR (400 MHz, CDCl3, 298 K) of R -3: δ H = 7.92 (d, J = 9.0 Hz, 2H),7.73 (d, J = 8.7 Hz, 2H), 7.43 (dd, J 1= 8.4 Hz, J 2= ​​1.8 Hz, 2H), δ 7.34 (s, 2H),7.32 (d, J = 9.0 Hz, 2H), 4.57 (m, 4H), 4.16 (m, 4H), 1.18 (t, J = 7.1 Hz, 6H). 13 CNMR (100 MHz, CDCl3, 298 K) of R -3: δ C HR-ESI-MS: calculated for C 28 H 24 Br2NaO6([ M +Na] + ): 638.9812; found 638.9813.

[0113] (2) A Schlenk tube containing Ni(cod)2 (154 mg, 0.56 mmol), cod (70 mg, 0.65 mmol), 2,2'-bipyridine (90 mg, 0.58 mmol), toluene (0.3 ml) and DMF (0.3 ml) was stirred at 90 °C for 30 min under N2 atmosphere. Then, a solution of Ni(cod)2 dissolved in toluene (2.4 mL) was added. R -3, and the mixture was stirred at 90 ° C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. RRR -2 (23.9 mg, 0.013 mmol) and RRRR -2 (21.6 mg, 0.012 mmol)

[0114] 1 H NMR (400 MHz, CDCl3, 298 K) of RRR -2: δ H = 7.82 (d, J = 9.1 Hz, 6H), 7.64 (d, J = 8.4 Hz, 6H), 7.29 (d, J = 9.2 Hz, 6H), 7.25 (d, J = 8.4 Hz, 6H), 6.95 (s, 6H), 4.62–4.51 (m, 12H), 4.14 (q, J = 7.1 Hz, 12H), 1.18 (t, J = 7.1Hz, 18H).

[0115] 1 H NMR (400 MHz, CDCl3, 298 K) of RRRR -2: δ H = 7.84 (d, J = 9.0 Hz, 8H),7.64 (d, J = 8.5 Hz, 8H), 7.37 (s, 8H), 7.31 (d, J = 8.7 Hz, 8H), 7.29 (d, J = 9.0Hz, 8H), 4.52 (dd, J 1= 18.8 Hz, J2= ​​16.4 Hz, 16H), 4.11 (q, J = 7.1 Hz, 16H),1.14 (t, J = 7.1 Hz, 24H). 13 C NMR (100 MHz, CDCl3, 298 K) of RRRR -2: δ C HR-ESI-MS: calculated for C 112 H 96 NaO 24 ([ M +Na] + ):1848.6218; found 1848.6212. Example

[0116] A new chiral macrocycle based on the BINOL skeleton RRRR -3 and RRRR -4, prepared by the following specific reaction steps:

[0117] (1) RRRR A mixture of -2 (50 mg, 0.027 mmol), 20% aqueous NaOH (1.0 ml), THF (1.0 ml), and CH3OH (1.8 ml) was stirred at 90°C overnight. The mixture was evaporated under reduced pressure. The crude product was purified by spherical C18 silica gel column chromatography (H2O to H2O / CH3CN = 10 / 1) to obtain the title compound as a white solid. RRRR -3 (47 mg, 0.027 mmol), 100 mg solid RRRR -3 was dissolved in water, 10 ml of 1M hydrochloric acid was added, and after stirring for 10 min, the precipitated white precipitate was filtered and washed with 10 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. RRRR -4. 1 H NMR (400 MHz, CDCl3, 298 K) of RRRR -3: δ H = 8.05 (d, J = 9.2 Hz, 8H), 7.76(d, J = 8.5 Hz, 8H), 7.40 (d,J = 9.2 Hz, 8H), 7.25 (s, 8H), 7.22 (d, J = 8.5 Hz,8H), 4.50 (d, J = 16.3 Hz, 8H), 4.39 (d, J = 16.3 Hz, 8H). 13 C NMR (100 MHz, CDCl3,298 K) of RRRR -3: δ C = 176.88, 166.63, 154.32, 132.83, 129.86, 128.28, 123.58,123.11, 118.76, 115.52, 68.97, 23.30. HR-ESI-MS: calculated for C 96 H 59 NaO 24 ([ M -7Na+3H] 4+ ): 404.8337; found 404.8336. Example

[0118] A series of new chiral macrocycles based on the BINOL skeleton SS -1, SSS -1 and SSSS -1, prepared by the following specific reaction steps:

[0119] (1) Compound S A mixture of -1 (1 g, 2.25 mmol) and THF (30 mL) was stirred at 0°C for 10 min. NaH was added to the mixture, and stirring was continued at 0°C for 10 min. Bromomethyl methyl ether was added to the mixture, and the reaction was allowed to react at room temperature for 12 hours. Extraction was performed with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. S -2 (2.0 g, 3.2 mmol), 1 HNMR characterization was consistent with S chirality.

[0120] (2) A Schlenk tube containing Ni(cod)2 (384 mg, 1.4 mmol), cod (0.2 ml, 1.63 mmol), 2,2'-bipyridine (224 mg, 1.43 mmol), toluene (1.1 ml) and DMF (1.1 ml) was stirred at 90 °C for 30 min under N2 atmosphere. Then, Ni(cod)2 dissolved in toluene (5.4 mL) was added. S -2, and the mixture was stirred at 90 °C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. SS -1, SSS -1 and SSSS -1.

[0121] 1 H NMR (400 MHz, CDCl3, 298 K) of SS -1: δ H = 7.87 (d, J = 9.0 Hz, 4H), 7.72 (d, J = 8.3 Hz, 4H), 7.54 (d, J = 9.0 Hz, 4H), 7.23 (dd, J = 8.2, 1.6Hz, 4H), 6.95 (s, 4H), 5.07 (d, J = 6.6 Hz, 4H), 4.91 (d, J = 6.6 Hz, 4H), 3.21 (s, 12H).

[0122] 1 H NMR (400 MHz, CDCl3, 298 K) of SSS -1: δ H = 7.83 (d, J = 9.0 Hz, 6H), 7.65 (d, J = 8.4 Hz, 6H), 7.51 (d, J = 9.0 Hz, 6H), 7.10 (d, J = 8.4 Hz, 6H), 6.91 (s, 6H), 5.19 (d, J = 6.8 Hz, 6H), 4.98 (d, J = 6.8 Hz, 6H), 3.11 (s,18H).

[0123] 1H NMR (400 MHz, CDCl3, 298 K) of SSSS -1: δ H = 7.83 (d, J = 9.0 Hz, 8H), 7.64 (d, J = 8.5 Hz, 8H), 7.54 (d, J = 9.1 Hz, 8H), 7.33 (s, 8H), 7.22 (d, J = 8.9 Hz, 8H), 5.08 (d, J = 6.7 Hz, 8H), 5.01 (d, J = 6.7 Hz, 8H), 3.12(s, 24H).

[0124] Example 5

[0125] A series of new chiral macrocycles based on the BINOL skeleton SSS -2 and SSSS -2, prepared by the following specific reaction steps:

[0126] (1) Compound S A mixture of -1 (1.5 g, 3.4 mmol), Cs2CO3 (8.8 g, 27.2 mmol), ethyl bromoacetate (1.1 ml, 10 mmol), and DMF (20 mL) was stirred at 40 °C for 24 hours. Saturated NH4Cl solution was added to the mixture, extracted with CH2Cl2, and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2) to obtain the title compound as a white solid. S -3.

[0127] 1 H NMR (400 MHz, CDCl3, 298 K) of S -3: δ H = 7.91 (d, J = 9.1 Hz, 2H),7.72 (d, J = 8.7 Hz, 2H), 7.43 (dd, J 1= 8.7 Hz, J 2=1.8 Hz, 2H), δ 7.35 (s, 2H),7.31 (d, J = 9.3 Hz, 2H), 4.56 (m, 4H), 4.16 (m, 4H), 1.17 (t, J = 7.2 Hz, 6H). 13CNMR (100 MHz, CDCl3, 298 K) of S -3: δ C = 167.90, 153.24, 134.09, 128.91, 128.66,127.07, 126.62, 126.31, 120.37, 117.55, 114.12, 65.63, 60.16, 13.06.

[0128] (2) A Schlenk tube containing Ni(cod)2 (154 mg, 0.56 mmol), cod (70 mg, 0.65 mmol), 2,2'-bipyridine (90 mg, 0.58 mmol), toluene (0.3 ml) and DMF (0.3 ml) was stirred at 90 °C for 30 min under N2 atmosphere. Then, a solution of Ni(cod)2 dissolved in toluene (2.4 mL) was added. S -3, and the mixture was stirred at 90 ° C for 24 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 / EtOAc = 20 / 1) to obtain the target chiral macrocyclic compound as a white solid. SSS -2 and SSSS -2.

[0129] 1 H NMR (400 MHz, CDCl3, 298 K) of SSS -2: δ H = 7.82 (d, J = 9.0 Hz, 6H), 7.64 (d, J = 8.5 Hz, 6H), 7.29 (d, J = 9.2 Hz, 6H), 7.25 (d, J = 8.4 Hz, 6H), 6.95 (s, 6H), 4.65–4.52 (m, 12H), 4.13 (q, J = 7.1 Hz, 12H), 1.18 (t, J = 7.1Hz, 18H).

[0130] 1 H NMR (400 MHz, CDCl3, 298 K) of SSSS -2: δ H = 7.83 (d, J = 9.1 Hz, 8H),7.62 (d, J= 8.5 Hz, 8H), 7.34 (s, 8H), 7.34 (d, J = 8.7 Hz, 8H), 7.29 (d, J = 9.0Hz, 8H), 4.51 (dd, J 1= 18.8 Hz, J 2= ​​16.4 Hz, 16H), 4.10 (q, J = 7.2 Hz, 16H), 1.05(t, J = 7.2 Hz, 24H). 13 C NMR (100 MHz, CDCl3, 298 K) of SSSS -2:: δ C = 169.31,153.84, 138.38, 133.89, 129.25, 128.93, 128.02, 123.92, 123.28, 120.47,115.28, 67.11, 60.96, 14.00. Example

[0131] A new chiral macrocycle based on the BINOL skeleton SSSS -3 and SSSS -4, prepared by the following specific reaction steps:

[0132] (1) SSSS- A mixture of 2 (50 mg, 0.027 mmol), 20% aqueous NaOH (1.0 ml), THF (1.0 ml), and CH3OH (1.8 ml) was stirred at 90°C overnight. The mixture was evaporated under reduced pressure. The crude product was purified by spherical C18 silica gel column chromatography (H2O to H2O / CH3CN = 10 / 1) to obtain the title compound as a white solid. SSSS -3. 100 mg solid SSSS -3 was dissolved in water, 10 ml of 1M hydrochloric acid was added, and after stirring for 10 min, the precipitated white precipitate was filtered and washed with 10 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. SSSS -4. 1 H NMR (400 MHz, CDCl3, 298 K) of SSSS -3: δ H = 8.00 (d, J = 9.2 Hz, 8H), 7.73 (d, J = 8.8 Hz, 8H),7.36 (d,J = 9.2 Hz, 8H), 7.23 (s, 8H), 7.20 (d, J = 8.5 Hz, 8H), 4.47 (d, J = 14.7Hz, 8H), 4.36 (d, J = 14.7 Hz, 8H). 13 C NMR (100 MHz, CDCl3, 298 K) of SSSS -3: δ C = 176.93, 164.03, 154.21, 132.98, 129.81, 128.31, 123.52, 122.51, 118.53,115.17, 68.43, 23.20. Example

[0133] (1) Water-soluble macrocycles RRRR- Recognition properties of achiral guests adamantane G2 (commercially available) and calendula G8 (commercially available):

[0134] By tracking the titration of different equivalents of the guest RRRR Fluorescence titration experiments were performed using Origin Lab 9.1 software and a 1:1 binding model (Guo, D.-S.; Uzunova, VD; Su, X.; Liu, Y.; Nau, WM). Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions. Chem. Sci .2011, 2 , 1722–1734) was fitted to the fluorescence intensity versus guest concentration plot to calculate the binding constant. K a. Download the fitting module from Professor Nau's group website (http: / / www.jacobs-university.de / ses / wnau) under the "Fitting Function" column. Detailed description is as follows:

[0135] i) The concentration is 0.025 μM RRRR-3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, continue to add G2 until 0.40 μM, monitor the change curve of fluorescence intensity, and Figure 1 As can be seen from (a), the fluorescence intensity of the mixture gradually increases. Further fitting the fluorescence intensity change of the mixture at a wavelength of 400nm, from Figure 1 As can be seen from (b), the binding constant K a After fitting, it was determined to be (3.08±0.99)×10 8 M −1 .

[0136] ii) Match RRRR -3 concentration was 0.025 μM and G8 concentration was 0.020 μM RRRR Take 2.5 ml of the mixture of G2 and G8 in a cuvette, excite with a wavelength of 300 nm, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add G2 until it reaches 51.3 μM. Monitor the change curve of the fluorescence intensity. Figure 1 As can be seen from (c), the fluorescence intensity of the mixture gradually increases. Further fitting the fluorescence intensity change of the mixture at a wavelength of 400 nm, from Figure 1 As can be seen from (d), the binding constant K a After fitting, it was determined to be (8.57±0.82)×10 10 M −1 . Figure 1 (c) The inset shows the total molar concentration of 0.25 μM. RRRR The job plot of the fluorescence emission changes of -3 and G8 at 400 nm shows that the host-guest binding model conforms to 1:1.

[0137] Example 8

[0138] (1) Water-soluble macrocycles RRRR- 3. Recognition properties of the chiral guest SPINOL (commercially available):

[0139] By tracking the titration of different equivalents of the guest RRRRFluorescence titration experiments were performed using Origin Lab 9.1 software and a 1:1 binding model (Guo, D.-S.; Uzunova, VD; Su, X.; Liu, Y.; Nau, WM). Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions. Chem. Sci .2011, 2 , 1722–1734) was fitted to the fluorescence intensity versus guest concentration plot to calculate the binding constant. K a. Download the fitting module from Professor Nau's group website (http: / / www.jacobs-university.de / ses / wnau) under the "Fitting Function" column. Detailed description is as follows:

[0140] i) The concentration of 2.5 μM SSSS -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( S )-SPINOL to 70 μM, monitor the change curve of fluorescence intensity, and further fit the change of the mixture fluorescence intensity at a wavelength of 400 nm. Figure 2 As can be seen in (a), the fluorescence intensity of the mixture gradually increases. Figure 2 (b), Binding constant K a After fitting, it was determined to be (9.88±2.51)×10 4 M −1 .

[0141] ii) with a concentration of 2.5 μM RRRR -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( S )-SPINOL to 650 μM, monitor the change curve of fluorescence intensity, and further fit the change of fluorescence intensity of the mixture at a wavelength of 400 nm. Figure 2 As can be seen in (c), the fluorescence intensity of the mixture gradually decreases. Figure 2 (d), binding constant K aAfter fitting, it was determined to be (5.26±1.13)×10 3 M −1 .

[0142] iii) with a concentration of 2.5 μM SSSS -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( R )-SPINOL to 700 μM, monitor the change curve of fluorescence intensity, and further fit the change of the mixture fluorescence intensity at a wavelength of 400 nm. Figure 2 As can be seen in (e), the fluorescence intensity of the mixture gradually decreases. Figure 2 (f), binding constant K a After fitting, it was determined to be (5.34±0.91)×10 3 M −1 .

[0143] iv) with a concentration of 2.5 μM RRRR -3 aqueous solution, take 2.5 ml and add it to the cuvette, use 300 nm wavelength to excite, measure the fluorescence spectrum of the solution in the wavelength range of 350–550 nm, and continuously add ( R )-SPINOL to 45 μM, monitor the change curve of fluorescence intensity, and further fit the change of the mixture fluorescence intensity at a wavelength of 400 nm. Figure 2 As can be seen in (g), the fluorescence intensity of the mixture gradually decreases. Figure 2 (h), binding constant K a After fitting, it was determined to be (8.65±2.03)×10 4 M −1 .

[0144] analyze Figure 4 The data obtained can be used to conclude that water-soluble macrocyclic RRRR- The enantioselectivity of 3 for the chiral guest SPINOL ( K S / K R or K R / K S ) reached 18.8.

[0145] Example 9

[0146] Water-soluble macrocycles RRRR- Identification properties of steroid compound 3 - megestrol acetate:

[0147] By tracking the titration of different equivalents of the guest RRRR Fluorescence titration experiments were performed using Origin Lab 9.1 software and a 1:1 binding model (Guo, D.-S.; Uzunova, VD; Su, X.; Liu, Y.; Nau, WM). Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions. Chem. Sci .2011, 2 , 1722–1734) was fitted to the fluorescence intensity versus guest concentration plot to calculate the binding constant. K a. Download the fitting module from Professor Nau's group website (http: / / www.jacobs-university.de / ses / wnau) under the "Fitting Function" column. Detailed description is as follows:

[0148] i) Prepare an aqueous solution of a mixture of RRRR-3 and G8 with a concentration of 0.025 μM RRRR-3 and 0.025 μM G8, take 2.5 ml and add it to a cuvette. Excite with a wavelength of 300 nm and measure the fluorescence spectrum of the solution in the wavelength range of 350-550 nm. Continuously add megestrol acetate to 75 μM and monitor the change curve of the fluorescence intensity. Figure 3 As can be seen from (a), the fluorescence intensity of the mixture gradually increases. Further fitting the fluorescence intensity change of the mixture at a wavelength of 400 nm, from Figure 3 As can be seen in (b), the binding constant Ka was determined to be (4.37 ± 0.29) × 10 10 M −1 .analyze Figure 3 The data obtained can be concluded that the water-soluble macrocyclic RRRR-3 has a strong recognition ability for the steroid compound megestrol acetate.

[0149] Example 10

[0150] Water-soluble macrocycles RRRR- 3. SSSS- Array sensing of 3 pairs of 14 steroid compounds is used to distinguish steroid compounds. The specific operation is as follows.

[0151] Determination of water-soluble macrocycles RRRR- 3. SSSS-3 pairs of 14 steroid compounds fluorescence sensor array, the sensor array consists of a series of water-soluble macrocyclic RRRR- 3. SSSS- 3 and steroid compounds of different concentrations form sensing units. The characteristic spectrum generated by each sensing unit in response to 14 steroid compounds can realize the identification and detection of specific substances. The fluorescence sensor array has the advantages of high sensitivity, no need for a reference system, rich output signals, and the ability to image. It has become the focus of sensor array development in recent years.

[0152] from Figure 3 It can be seen that Figure 3 (a) SSSS- 3 can distinguish 8 steroid compounds, Figure 3 (b) RRRR- 3 can distinguish 10 steroid compounds, and two chiral water-soluble macrocyclic SSSS- 3 and RRRR- 3 together achieved the distinction of 14 steroid compounds, further demonstrating the importance of chirality in the sensing of this array.

[0153] The above content is a partial list of preferred embodiments of the present invention, but the present invention should not be limited to the content disclosed in these examples. Therefore, any equivalents or modifications that do not depart from the spirit of the present invention fall within the scope of protection of the present invention. A small number of necessary terms are used in the description and illustration, and they do not constitute limitations of the invention.

Claims

1. A chiral supramolecular macrocycle based on a binaphthol motif, characterized in that: The general structural formula is as follows: ； in: 【1】When the structural formula The three-dimensional conformation of the part is When, and (1) n = 2, R' = CH2OCH3: macrocyclic RR -1 (2) n = 3, R' = CH2OCH3: macrocyclic RRR -1 (3) n = 3, R' = CH2COOCH2CH3: macrocyclic RRR -2 (4) n = 4, R' = CH2OCH3: macrocyclic RRRR -1 (5) n = 4, R' = CH2COOCH2CH3: macrocyclic RRRR -2 (6) n = 4, R' = CH2COONa: macrocyclic RRRR -3 (7) n = 4, R' = CH2COOH: macrocyclic RRRR -4; 【2】 When the structural formula The three-dimensional conformation of the part is When, and (1) n = 2, R' = CH2OCH3: macrocyclic SS -1 (2) n = 3, R' = CH2OCH3: macrocyclic SSS -1 (3) n = 3, R' = CH2COOCH2CH3: macrocyclic SSS- 2 (4) n = 4, R' = CH2OCH3: macrocyclic SSSS -1 (5) n = 4, R' = CH2COOCH2CH3: macrocyclic SSSS -2 (6) n = 4, R' = CH2COONa: macrocyclic SSSS -3 (7) n = 4, R' = CH2COOH: macrocyclic SSSS -4.

2. The method for preparing the chiral supramolecular macrocycle based on the binaphthol motif according to claim 1, characterized in that: Big Ring RR -1, RRR -1, RRRR -1 Its preparation method is as follows: Ni(cod)2 0.46 mmol~0.66 mmol, cod 0.55 mmol~0.75 mmol, 2,2'-bipyridine 0.48 mmol~0.68 mmol, toluene 0.2 ml~0.4 ml and DMF 0.2 ml~0.4 ml were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere; then, the 2-hydroxy-2-nitropropene dissolved in 2 ml~4 ml toluene was added. R -2 0.12~0.34mmol, and the mixture was stirred at 90 °C for 24~72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4) and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0~20 / 1 to obtain the target chiral macrocyclic compound as a white solid. RR -1, RRR -1 and RRRR -1; in R The structure of -2 is .

3. The method for preparing the chiral supramolecular macrocycle based on the binaphthol motif according to claim 1, characterized in that: Big Ring SS -1, SSS -1, SSSS -1 Its preparation method is as follows: Ni(cod)2 0.46 mmol~0.66 mmol, cod 0.55 mmol~0.75 mmol, 2,2'-bipyridine 0.48 mmol~0.68 mmol, toluene 0.2 ml~0.4 ml and DMF 0.2 ml~0.4 ml were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere. Then, the solution dissolved in 2 ml~4 ml toluene was added. S -2 0.12~0.34 mmol, and the mixture was stirred at 90 °C for 24~72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids, and the filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4) and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0~20 / 1 to obtain the target chiral macrocyclic compound as a white solid. SS -1, SSS -1 and SSSS -1; in S The structure of -2 is .

4. The method for preparing the chiral supramolecular macrocycle based on the binaphthol motif according to claim 1, characterized in that: Big Ring RRR -2 and RRRR -2 Its preparation method is as follows: Ni(cod)2 0.46 mmol~0.66 mmol, cod 0.55 mmol~0.75 mmol, 2,2'-bipyridine 0.48 mmol~0.68 mmol, toluene 0.2 ml~0.4 ml and DMF 0.2 ml~0.4 ml were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere. Then, the solution dissolved in 2 ml~4 ml toluene was added. R -3 0.12~0.34mmol, and the mixture was stirred at 90 °C for 24~72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids, and the filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4) and evaporated under reduced pressure; the crude product was purified by silica gel column chromatography with a CH2Cl2 / EtOAc solvent ratio of 1 / 0~20 / 1 to obtain the target chiral macrocyclic compound as a white solid. RRR -2 and RRRR -2; in R The structure of -3 is .

5. The method for preparing the chiral supramolecular macrocycle based on the binaphthol motif according to claim 1, characterized in that: Big Ring SSS -2 and SSSS -2 Its preparation method is as follows: Ni(cod)2 0.46 mmol~0.66 mmol, cod 0.55 mmol~0.75 mmol, 2,2'-bipyridine 0.48 mmol~0.68 mmol, toluene 0.2 ml~0.4 ml and DMF 0.2 ml~0.4 ml were placed in a Schlenk tube and stirred at 90 °C for 30~50 min under N2 atmosphere; then, the solution dissolved in 2 ml~4 ml toluene was added. S -3 0.12-0.34 mmol, and the mixture was stirred at 90 °C for 24-72 hours. After cooling to room temperature, the mixture was filtered through celite to remove solids. The filtrate was collected and evaporated under reduced pressure, then extracted with CH2Cl2 and washed with brine. The organic layers were combined, dried (Na2SO4), and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography using CH2Cl2 / EtOAc solvent ratios of 1 / 0 to 20 / 1 to obtain the target chiral macrocyclic compound as a white solid. SSS -2 and SSSS -2; in S The structure of -3 is .

6. The method for preparing the chiral supramolecular macrocycle based on binaphthol motif according to claim 1, characterized in that: Big Ring RRRR -3 and RRRR -4 Its preparation method is as follows: Will RRRR A mixture of 0.027 mmol of 2-hydroxy-2-propene, 1 ml to 2 ml of 20% aqueous NaOH, 1 ml to 2 ml of THF, and 1 ml to 2 ml of CH3OH was stirred at 90 °C for 12 h to 24 h, and the mixture was evaporated under reduced pressure; the crude product was purified by spherical C18 silica gel column chromatography with H2O to H2O / CH3CN = 10 / 1 to obtain the target compound as a white solid. RRRR -3; 100 mg RRRR -3 solid was dissolved in water, 10~20 ml of 1M hydrochloric acid was added, and after stirring for 10~20 min, the precipitated white precipitate was filtered and washed with 10~20 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. RRRR -4.

7. The method for preparing the chiral supramolecular macrocycle based on the binaphthol motif according to claim 1, characterized in that: Big Ring SSSS -3 and SSSS -4, its synthesis steps are as follows: Will SSSS A mixture of 0.027 mmol of 2-Hydroxy-2-nitropropene, 1 ml to 2 ml of 20% aqueous NaOH, 1 ml to 2 ml of THF, and 1 ml to 2 ml of CH3OH was stirred at 90 °C for 12 h to 24 h. The mixture was evaporated under reduced pressure, and the crude product was purified by spherical C18 silica gel column chromatography to H2O to H2O / CH3CN = 10 / 1 to obtain the target compound as a white solid. SSSS -3, 100 mg SSSS -3 solid was dissolved in water, 10~20 ml of 1M hydrochloric acid was added, and after stirring for 10~20 min, the precipitated white precipitate was filtered and washed with 10~20 ml of 1M hydrochloric acid. The filter residue obtained was the target compound as a white solid. SSSS -4.

8. The use of the chiral supramolecular macrocycle based on binaphthol motif according to claim 1 in non-diagnostic or non-therapeutic detection, characterized in that: The chiral supramolecular macrocycle recognizes chiral or achiral molecules. The non-diagnostic or non-therapeutic detection applications include the recognition and sensing of steroids and the differentiation of steroid compounds through fluorescence array sensing.

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