Aromatic oligopolyamide folding body with protected amino alkoxy side chain as well as preparation method and application of aromatic oligopolyamide folding body

Abstract

The invention relates to an aromatic oligo-polyamide folded body with a protected amino alkoxy side chain and a preparation method and application thereof, the aromatic oligo-polyamide folded body has the following structure: # imgabs0 # R'is independently selected from a linear alkyl group, a branched alkyl group and # imgabs1 # in each repeating unit, m is equal to 0 to 2, and # imgabs2 # appears at least once; r ''is selected from the group consisting of a linear alkyl group, a branched alkyl group, and # imgabs3 # n = 1 to 8. Compared with the prior art, the aromatic oligo-polyamide folding body prepared by the invention has a protected amino alkoxy side chain, the amino reaction activity is good after a protecting group is removed, and a further functionalized folding body sequence can be conveniently obtained by using various reagents so as to construct a supramolecular secondary assembly system; and a biomacromolecule interaction mechanism is expected to be disclosed.

Description

Technical Field

[0001] The invention relates to the technical field of aromatic oligoamide foldamer compounds, in particular to an aromatic oligoamide foldamer with a protected aminoalkoxy side chain and a preparation method and application thereof. Background Art

[0002] The supramolecular system, which is a system beyond the molecular level constructed by using hydrogen bonds, cation-π interactions, π-π stacking and other interactions between the same or different molecules, is a research hotspot with broad application prospects. This type of system is not only expected to simulate the functions of biological macromolecules and achieve sustained drug release, but also provides many new ideas for basic chemical research.

[0003] The secondary assembly of supramolecular systems is at the forefront of research and has more practical applications. By modifying the supramolecular system, multiple supramolecular systems can interact with each other again (the strength of this interaction force is usually weaker than the strength of the first-order force of the supramolecular system). The secondary assembly obtained not only has a significant increase in overall bonding strength, but also has the potential to obtain a system with doubled molecular weight; supramolecular polymers are such an example.

[0004] The multilevel structure of a protein is an example of this secondary assembly. The hydrogen bond interactions between the peptide bonds of a polypeptide and the hydrophobic interactions between the amino acid residues give rise to secondary structures such as α-helices. The interactions between these secondary structures (secondary assembly) can give rise to tertiary and quaternary structures such as protein domains.

[0005] Different from the foldamers of (quasi) polypeptide sequences obtained by condensation of aliphatic amino acids, aromatic oligoamide foldamers benefit from the rigid structure and π-π stacking effect of the aromatic core, which not only exhibits better conformational stability but also makes it possible to construct unique supramolecular assemblies such as helical molecular capsules and foldamer pseudorotaxanes.

[0006] At the same time, constructing secondary interactions in supramolecular systems by means of multiple hydrogen bond interactions and metal multidentate coordination to obtain larger supramolecular systems has become a field of great significance in chemical biology and supramolecular chemistry for revealing the interactions between biomacromolecules.

[0007] However, introducing structural units that can form secondary assemblies into a supramolecular system often requires complex organic synthesis methods and expensive activation reagents to activate reaction sites with poor reactivity and achieve functionalization. Summary of the invention

[0008] The purpose of the present invention is to provide an aromatic oligoamide foldamer with protected aminoalkoxy side chains and a preparation method and application thereof. The protected aminoalkoxy side chains of the aromatic oligoamide foldamer can be deprotected under mild conditions to easily obtain a further functionalized foldamer sequence, which can be used to construct a supramolecular secondary assembly system.

[0009] The purpose of the present invention can be achieved by the following technical solutions:

[0010] In one aspect, the present invention provides an aromatic oligomer amide folded body with a protected aminoalkoxy side chain, wherein the aromatic oligomer amide folded body has the following structure:

[0011]

[0012] R' in each repeating unit is independently selected from linear alkyl, branched alkyl and (tert-butyloxycarbonyl protected aminoalkyl), wherein m=0 to 2, and Appears at least once;

[0013] R" is selected from the group consisting of linear alkyl, branched alkyl and (9-fluorenylmethyl);

[0014] n=1 to 8.

[0015] In the present invention, The position of the * is the position where the group is broken, that is, the O atom is connected to the C atom on the left side of the aromatic oligoamide folded body structural formula.

[0016] Preferably, the R' in each repeating unit is independently selected from propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, isopentyl and Where m = 0 to 2, and Occurs at least once.

[0017] Preferably, wherein R" is selected from propyl, isopropyl, butyl, isobutyl, tert-butyl and

[0018] Preferably, the aromatic oligoamide foldable body comprises compound A1, A2 or A3, wherein the structural formula of A1 is:

[0019]

[0020] The structural formula of A2 is:

[0021]

[0022] The structural formula of A3 is:

[0023]

[0024] In a second aspect, the present invention provides a method for preparing the above-mentioned aromatic oligoamide folded body with protected aminoalkoxy side chains.

[0025] Preferably, when the aromatic oligoamide folded body is compound A1, the preparation process comprises the following steps: using compound 7 as a starting material, first reacting it with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, and then reacting the acyl chloride residue with a mixture of diisopropylethylamine and compound 8 to obtain compound A1. The reaction process is shown below:

[0026]

[0027] The structural formula of compound 8 is

[0028] Preferably, when the aromatic oligoamide folded body is compound A2, the preparation process comprises the following steps: using compound 3 as a raw material, first reacting it with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, and then reacting the acyl chloride residue with a mixture of diisopropylethylamine and compound 9 to obtain compound A2. The reaction process is shown below:

[0029]

[0030] The structural formula of compound 3 is The structural formula of compound 9 is

[0031]

[0032] Preferably, the specific preparation process of compound 3 is as follows: compound 1 is used as a raw material, reacted with diisopropylethylamine and isopropyl chloroformate in an organic solvent to obtain compound 2, and compound 2 is reacted with tetrahydrofuran and sodium hydroxide to obtain compound 3. The reaction process is as follows:

[0033]

[0034] Preferably, when the aromatic oligoamide folded body is compound A3, the preparation process comprises the following steps: using compound 6 as a raw material, first reacting it with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, and then reacting the acyl chloride residue with a mixture of diisopropylethylamine and compound 10 to obtain compound A3. The reaction process is shown below:

[0035]

[0036] The structural formula of compound 6 is The structural formula of compound 10 is

[0037]

[0038] Preferably, the specific preparation process of compound 6 is as follows: compound 3 is used as a raw material, reacted with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, the acyl chloride residue is reacted with compound 4 and diisopropylethylamine to obtain compound 5, and compound 5 is reacted with lithium hydroxide monohydrate added to a tetrahydrofuran solution to obtain compound 6. The reaction process is as follows:

[0039]

[0040] In a third aspect, the present invention also provides an application of the above-mentioned aromatic oligoamide foldamer with protected aminoalkoxy side chains, wherein the aromatic oligoamide foldamer is used to construct a supramolecular secondary assembly system.

[0041] Preferably, the protected aminoalkoxy side chains of the aromatic oligoamide foldable body can be deprotected under mild conditions, and the exposed amino groups have high reactivity and can be further functionalized and used to construct supramolecular secondary assembly systems.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] (1) The present invention designs an aromatic oligoamide foldamer compound having a protected aminoalkoxy side chain, which can be further derivatized to obtain an aromatic oligoamide foldamer compound for use in supramolecular secondary assemblies.

[0044] (2) The present invention designs an aromatic oligoamide foldamer compound based on 8-fluoroquinoline and pyridine monomers, the protected aminoalkoxy side chain of which can be deprotected under mild conditions, and the exposed amino group has high reactivity.

[0045] (3) The aromatic oligoamide foldamer compound designed by the present invention has a protected aminoalkoxy side chain at a specific position in the oligomeric sequence. The amino group has good reactivity after removing the protecting group, and can be conveniently used with various types of reagents to obtain a further functionalized foldamer sequence to construct a supramolecular secondary assembly system.

[0046] (4) The method for preparing the aromatic oligoamide foldamer compound of the present invention has mild reaction conditions, stable reaction, easy operation and good product yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 is the structural formula of the aromatic oligoamide foldable body of the present invention;

[0048] Figure 2 This is the synthetic route of compounds 1 to 6 of the present invention;

[0049] Figure 3 The synthetic routes of compounds A1, A2 and A3 of the present invention (in the figure, A is the synthetic route of compound A1, B is the synthetic route of compound A2, C is the synthetic route of compound A3, and D is the structural formula of compounds 8 and 10). DETAILED DESCRIPTION

[0050] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0051] Unless otherwise specified, the reagents, methods, instruments and equipment used in the present invention are conventional reagents, methods, instruments and equipment in the art. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0052] The structural formula of an aromatic oligoamide folded body with a protected aminoalkoxy side chain of the present invention is as follows Figure 1 shown.

[0053] The preparation method of the present invention can be further embodied by the preparation process of representative compounds as follows:

[0054] Among them, compound 4 is an existing conventional compound.

[0055] Example 1: Synthesis of compounds 1 to 6, the synthetic route is as follows Figure 2 Shown

[0056] Synthesis of compound 1

[0057] A solution of 8-fluoro-4-isopropoxy-7-nitroquinoline-2-carboxylic acid methyl ester (1.29 g, 4.0 mmol) in 72 mL of methanol / glacial acetic acid (v / v=1:1) was heated to reflux, and reduced iron powder (0.692 g, 12.4 mmol) was added in batches within 20 minutes. The reflux reaction was continued for 20 minutes and the yellow insoluble matter was filtered out; the filtrate was evaporated to remove the solvent and extracted with CH2Cl2, the reddish-brown insoluble matter was filtered out and washed with brine, the organic phase was dried over Na2SO4 and the solvent was evaporated to obtain compound 1 as a yellow solid (1.09 g, yield 95%).

[0058] 1H NMR (400MHz, CDCl3): δ / ppm=7.86(dd,9.0 / 1.5Hz,1H),7.41(s,1H),7,10(dd,9.0 / 7.7 Hz,1H),4.14(br,2H),4.06–4.00(m,5H),2.26(hept,6.7Hz,1H),1.12(d,6.7Hz,6H).

[0059] Synthesis of compound 2

[0060] Isopropyl chloroformate was added to a 15 mL anhydrous 1,4-dioxane solution containing compound 1 (500 mg, 1.71 mmol) and diisopropylethylamine (1.11 g, 8.55 mmol) at 0°C, and the mixture was heated to 80°C and stirred overnight. The mixture was washed with water and extracted with dichloromethane, and purified by silica gel column chromatography (10% → 25% ethyl acetate / petroleum ether, v / v) to obtain compound 2 (460 mg, yield 71%).

[0061] 1 H NMR (600MHz, CDCl3): δ / ppm=8.44(br,1H),7.94(d,9.3Hz,1H),7.44(s,1H),7.05(s,1H),5.01(hept,6.3 Hz,1H),3.99(s,3H),3.98(d,6.4Hz,2H),2.21(hept,6.7Hz,1H),1.28(d,6.2Hz,6H),1.06(d,6.7Hz,6H).

[0062] Synthesis of compound 3

[0063] To a solution of compound 2 (400 mg, 1.06 mmol) in 18 mL of tetrahydrofuran was added a 2 mL aqueous solution of sodium hydroxide (106 mg, 2.64 mmol). The mixture was stirred at room temperature for 3 hours and then treated with a 5% (w / w) aqueous solution of citric acid and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and the solvent was evaporated to obtain compound 3 (395 mg, yield ~100%), which was directly used in the next step after drying.

[0064] 1 H NMR (400MHz, CDCl3): δ / ppm=8.55(t,8.2Hz,1H),8.04(dd,9.4 / 1.8Hz,1H),7.57(s,1H),7.12(br,1H), 5.09(hept,6.3Hz,1H),4.08(d,6.5Hz,2H),2.35–2.24(m,1H),1.37(d,6.2Hz,6H),1.14(d,6.7Hz,6H).

[0065] Synthesis of compound 5

[0066] 1-Chloro-N,N,2-trimethylpropyleneamine (246 mg, 1.84 mmol) was added to a 4 mL anhydrous dichloromethane solution containing compound 3 (223 mg, 0.61 mmol), and the solvent was removed under reduced pressure after stirring at room temperature for 2 hours, and the mixture was dried under vacuum for 3 hours. The acid chloride residue was transferred to a 2 mL anhydrous dichloromethane solution containing compound 4 (201 mg, 0.51 mmol) and diisopropylethylamine (262 mg, 2.03 mmol) with 5 mL anhydrous dichloromethane, and stirred overnight at room temperature. The mixture was washed with a saturated sodium bicarbonate aqueous solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain a crude product. The white solid of compound 5 (330 mg, yield 87%) was obtained by precipitation with dichloromethane and methanol.

[0067] 1 H NMR (600MHz, CDCl3): δ / ppm=11.0(br,1H),8.93(dd,9.2Hz,6.5Hz,1H),8.51(br,1H),8.06(d, 9.2Hz,1H),8.04(d,9.2Hz,1H),7.69(s,1H),7.57(s,1H),7.16(s,1H),5.10(hept,6.1Hz,1H) ,4.78(br,1H),4.38(t,5.9Hz,2H),4.11(d,6.6Hz,2H),4.09(s,3H,COOCH3),3.45(q,7.7Hz,2 H,),2.31(hept,1H),2.24–2.16(m,2H),1.45(s,9H),1.38(d,6.3Hz,6H),1.15(d,6.7Hz,6H).

[0068] Synthesis of compound 6

[0069] To a solution of compound 5 (275 mg, 0.37 mmol) in 7 mL of tetrahydrofuran was added a solution of lithium hydroxide monohydrate (39 mg, 0.93 mmol) in 7 mL of water. The mixture was stirred at room temperature for 4 hours and then treated with a 5% (w / w) aqueous solution of citric acid and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and the solvent was evaporated to obtain compound 6 as a light yellow solid (245 mg, yield 90%), which was directly used in the next step after drying.

[0070] Example 2: Synthesis of an aromatic oligoamide foldamer compound A1 with a protected aminoalkoxy side chain, the synthetic route is as follows Figure 3 As shown in A

[0071] (1) Synthesis of Compound 7

[0072] To a 20 mL 1,4-dioxane solution containing compound 4 (802 mg, 2.04 mmol), 100 mL of a 5% (w / w) aqueous solution of sodium bicarbonate was added. A 20 mL 1,4-dioxane solution of methyl chloroformate (792 mg, 3.06 mmol) was added dropwise at 0°C over 30 minutes. Stirring was continued at 0°C for 1 hour and then stirred at room temperature overnight. Additional methyl chloroformate ~10.0 mmol was added until the reaction was complete; treated with 1 M hydrochloric acid and extracted with dichloromethane, the crude product was purified by silica gel flash column chromatography (10% → 38% ethyl acetate / petroleum ether, v / v) to obtain an ester compound. To a solution of the ester compound (1.00 g, 1.6 mmol) in 125 mL of anhydrous ethyl acetate was added lithium iodide (0.652 g, 4.9 mmol) as a solid, and the mixture was stirred at 80°C overnight. After concentration, the mixture was treated with a 5% aqueous solution of citric acid (w / w) and extracted with dichloromethane. The organic phase was dried and then subjected to ultrasonic dispersion with methanol. The yellow insoluble matter was filtered out as a crude product. The product was purified by silica gel flash column chromatography (dichloromethane → 12% methanol / dichloromethane, v / v) to obtain compound 7 as a yellow solid (635 mg, yield 65%).

[0073] 1 H NMR (400MHz, DMSO-d6): δ / ppm=9.99(s,1H),7.90(t,8.8Hz,4H),7.80(d,7.5Hz,2H),7.52(s,1H),7.43(t,7.4Hz,2H),7.35 (t,7.4Hz,2H),7.00(br,1H),4.49(d,6.9Hz,2H),4.32(q,7.0Hz,2H),3.19(q,6.6Hz,2H),1.99(t,6.4Hz,2H),1.35(s,9H).

[0074] (2) Synthesis of compound 8, structural formula Figure 3 D

[0075] 1-Chloro-N,N,2-trimethylpropyleneamine (0.343g, 2.57mmol) was added to a 10mL anhydrous dichloromethane solution containing a dimeric 8-fluoroquinoline carboxylic acid compound (0.527g, 0.83mmol), and the solvent was removed under reduced pressure at room temperature for 3 hours. The residue of the acyl chloride was transferred to a 5mL anhydrous dichloromethane solution containing an amino compound of tripyridine dichloro 8-fluoroquinoline amide (0.716g, 0.75mmol) and diisopropylethylamine (0.41g, 3.15mmol) with 10mL anhydrous dichloromethane, and stirred overnight at room temperature. The solvent was removed by rotary evaporation to obtain a crude product. The amino compound protected by tert-butyloxycarbonyl was purified by silica gel flash column chromatography (10%-40% ethyl acetate / petroleum ether, v / v). To a solution of the tert-butoxycarbonyl-protected amino compound (0.250 g, 0.16 mmol) in 1 mL of anhydrous dichloromethane was added trifluoroacetic acid (0.50 mL). The mixture was stirred at room temperature for 6 hours, quenched and washed with saturated aqueous sodium bicarbonate solution, and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporation to obtain compound 8 as a yellow solid (0.830 g, yield 70%).

[0076] 1 H NMR (600MHz, DMSO-d6): δ / ppm=11.48(s,1H),11.30(s,1H),11.03(s,1H),10.40(s,1H),10.08(s,1H),9.93(s,1H),9.25(s,1H) ),8.48(s,1H),8.10–6.53(m,21H),4.36–4.13(m,6H),4.03(q,7.2Hz,2H),2.40–2.31(m,4H),1.41–1.20(m,33H),0.68(s,9H).

[0077] (3) Synthesis of Compound A1

[0078] 1-Chloro-N,N,2-trimethylpropyleneamine (134 mg, 1.00 mmol) was added to a 3 mL anhydrous dichloromethane solution containing compound 7 (186 mg, 0.31 mmol), and the solvent was removed under reduced pressure at room temperature for 3 hours. The residue of the acyl chloride was transferred to a mixture containing compound 8 (380 mg, 0.25 mmol) and diisopropylethylamine (143 mg, 1.11 mmol) with 4.5 mL anhydrous dichloromethane and stirred overnight at room temperature. The crude product was purified by silica gel flash column chromatography (10% → 40% ethyl acetate / petroleum ether, v / v) and precipitated with dichloromethane and methanol to obtain a white solid of compound A1 (325 mg, yield 61%).

[0079] 1 H NMR (400MHz, DMSO-d6): δ / ppm=11.56(s,1H),11.27(s,1H),10.66(s,1H),10.34(s,1H),10.14(s,1H),1 0.03–9.90(m,2H),8.84(s,1H),8.40–8.24(m,2H),8.24–8.08(m,1H),7.94(d,7.6Hz,1H),7.85–7.64(m ,5H),7.62–7.34(m,9H),7.34–6.96(m,13H),6.92–6.82(m,2H),6.80–6.63(m,3H),4.45–3.65(m,14H), 2.42–2.30(m,4H),2.27–2.00(m,3H),1.48(s,9H),1.40–1.27(m,20H),1.21–1.13(m,6H),0.50(s,9H).

[0080] Example 3: Synthesis of an aromatic oligoamide foldamer compound A2 with a protected aminoalkoxy side chain, the synthetic route is as follows Figure 3 B

[0081] (1) Synthesis of Compound 9

[0082] To a 0.7 mL anhydrous dichloromethane solution containing A1 (100 mg, 0.05 mmol) was added 0.10 mL tris(2-aminoethylamine) (0.65 mmol), and the mixture was stirred at room temperature for 30 minutes, washed with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate; purified by silica gel flash column chromatography (10% → 55% ethyl acetate / petroleum ether, v / v) to give compound 9 (86 mg, yield 93%), which was directly used in the next step for condensation with acyl chloride.

[0083] (2) Synthesis of Compound A2

[0084] 1-Chloro-N,N,2-trimethylpropyleneamine (61 mg, 0.46 mmol) was added to a 1 mL anhydrous dichloromethane solution containing compound 3 (56 mg, 0.15 mmol), and the solvent was removed under reduced pressure after stirring at room temperature for 3 hours, and the mixture was dried under vacuum for 3 hours. The acid chloride residue was transferred to a mixture containing compound 9 (140 mg, 76 μmol) and diisopropylethylamine (39 mg, 0.30 mmol) with 1.5 mL anhydrous dichloromethane, and stirred overnight at room temperature. The crude product was purified by silica gel flash column chromatography (dichloromethane → 25% ethyl acetate / dichloromethane, v / v) to obtain compound A2 as a white solid (145 mg, yield 87%).

[0085] 1 H NMR (400MHz, DMSO-d6): δ / ppm=11.68(s,1H),11.24(s,1H),10.37(s,1H),10.25(s,1H),10.15(s,2H),9.96–9.77(m, 3H),8.82(s,1H),8.51–8.28(m,2H),8.07–7.95(m,2H),7.87–7.76(m,2H),7.75–7.64(m,2H),7.61–7.36(m,4H),7.33 –7.10(m,8H),7.08–6.58(m,9H),4.49–4.25(m,4H),4.23–4.09(m,3H),4.07–3.92(m,3H),3.90–3.79(m,2H),2.32–2. 09(m,7H),1.52(s,9H),1.45–1.29(m,15H),1.28–1.15(m,15H),0.87(d,6.2Hz,3H),0.54(d,6.3Hz,3H),0.34(s,9H).

[0086] Example 4: Synthesis of an aromatic oligoamide foldamer compound A3 with a protected aminoalkoxy side chain, the synthetic route is as follows Figure 3 C

[0087] (1) Synthesis of compound 10, structural formula Figure 3 D

[0088] 1-Chloro-N,N,2-trimethylpropyleneamine (0.091 g, 0.68 mmol) was added to a 2 mL anhydrous dichloromethane solution containing a dimerized 8-fluoroquinolinecarboxylic acid compound (0.128 g, 0.20 mmol), and the solvent was removed under reduced pressure at room temperature for 3 hours, and the mixture was dried under vacuum for 3 hours. The acid chloride residue was transferred to a 1 mL anhydrous dichloromethane solution containing compound 8 (0.250 g, 0.17 mmol) and diisopropylethylamine (0.094 g, 0.73 mmol) with 3 mL anhydrous dichloromethane, and stirred overnight at room temperature. The solvent was removed by rotary evaporation to obtain a crude product. The amino compound protected by tert-butyloxycarbonyl was purified by silica gel flash column chromatography (10%-35% ethyl acetate / petroleum ether, v / v). Trifluoroacetic acid (0.45 mL) was added to a solution of the tert-butyloxycarbonyl protected amino compound (0.250 g, 0.12 mmol) in 1 mL of anhydrous dichloromethane, and stirred at room temperature for 5 hours, quenched with a saturated aqueous sodium bicarbonate solution, washed, and extracted with dichloromethane, and the solvent was removed by rotary evaporation to obtain a crude product. Compound 8 was purified by silica gel flash column chromatography (10%-35% ethyl acetate / petroleum ether, v / v) to obtain a yellow solid (0.830 g, 70%).

[0089] 1 H NMR (400MHz, DMSO-d6): δ / ppm=11.69(s,1H),11.14(s,1H),10.47(s,1H),10.34(s,1 H),10.10(s,2H),9.96(s,1H),9.92(s,1H),9.84(s,1H),8.77(s,1H),8.32(t,7.6Hz ,1H),8.09–7.87(m,3H),7.85(d,7.5Hz,2H),7.78–7.14(m,13H),7.08–6.56(m,8H), 4.37–3.81(m,12H),2.41–2.20(m,6H),1.43–1.15(m,36H),1.03(s,9H),0.38(s,9H).

[0090] (2) Synthesis of Compound A3

[0091] 1-Chloro-N,N,2-trimethylpropyleneamine (61 mg, 0.46 mmol) was added to a 4.5 mL anhydrous dichloromethane solution containing compound 6 (125 mg, 0.172 mmol), and the solvent was removed under reduced pressure at room temperature for 3 hours. The residue of the acyl chloride was transferred to a mixture containing compound 10 (220 mg, 0.115 mmol) and diisopropylethylamine (60 mg, 0.46 mmol) with 7 mL anhydrous dichloromethane, and stirred overnight at room temperature. The mixture was washed with a saturated sodium bicarbonate aqueous solution and extracted with dichloromethane, purified by silica gel flash column chromatography (20% → 50% ethyl acetate / petroleum ether, v / v) and precipitated with dichloromethane and methanol to obtain compound A3 as a white solid (225 mg, yield 75%).

[0092] 1 H NMR (600MHz, CCl4 / DMSO-d6=1:5, v / v): δ / ppm=11.45(s,1H),11.28–11.01( m,1H),10.93–10.55(m,1H),10.38–10.18(m,1H),10.15–9.47(m,5H),8.69( s,1H),8.14–6.41(m,32H),4.42–3.92(m,13H),3.47–3.31(m,2H),2.45–2.0 9(m,9H),1.53(s,9H),1.40–1.15(m,42H),0.85(br,3H),0.68–0.31(m,9H).

[0093] Embodiment 5:

[0094] The protected side chain amino groups can be deprotected under mild conditions, and the exposed highly reactive amino groups can be further functionalized into oligomeric sequences through simple steps for constructing secondary assembly structures. Examples of deprotection, functionalization, and secondary assembly supramolecular polymerization are given below.

[0095] 6-tert-Butylisocytosine (100 mg, 0.60 mmol) and N,N′-carbonyldiimidazole (146 mg, 0.90 mmol) were dissolved in 2.5 mL of 1,4-dioxane and stirred at 60°C for 2 hours. The white precipitate was collected by filtration, washed thoroughly with acetone and dried in the shade to obtain the activated isocytosine compound (110 mg, yield 70%).

[0096] 1 H NMR (600MHz, CDCl3): δ / ppm=12.63(br,1H,N H C=O), 12.49(br,1H,Ar-N H ),8.71(s,1H,N-CH=N),7.60(s,C(=O)-NC H =CH-N),7.14(s,C(=O)-N-CH=C H -N),5.93(s,1H,C(=O)-C H =C),1.39(s,9H, t Bu).

[0097] To a 2.5 mL anhydrous 1,4-dioxane solution containing compound A3 (175 mg, 0.065 mmol), 3.0 mL of a 1,4-dioxane solution of hydrogen chloride was added, and the mixture was stirred at room temperature for 4 hours and then the solvent was removed by rotary evaporation to obtain the corresponding amine. The residual solid of the amine was dissolved in 3.5 mL anhydrous dichloromethane, and anhydrous triethylamine (29 mg, 0.288 mmol) and an activated isocytosine compound (26 mg, 0.100 mmol) were added. The mixture was stirred at 35°C overnight, and then washed with 1.0 M aqueous hydrogen chloride solution, saturated aqueous sodium bicarbonate solution and brine, and extracted with dichloromethane. The mixture was purified by silica gel flash column chromatography (0.5% → 3.0% methanol / dichloromethane, v / v) and precipitated with methanol / dichloromethane to obtain a white solid of compound A4 (135 mg, yield 75%).

[0098] 1H NMR (600MHz, CCl4 / DMSO-d6=1:5, v / v): δ / ppm=11.66–9.45(m,9H),8.69(s,1H),8.21–6.33(m,26H),5.86(s,1 H),4.55–3.92(m,12H),3.58(s,1H),2.43–2.13(m,7H),1.41–1.08(m,42H),0.85(br,3H),0.68–0.32(m,9H).

[0099] The nuclear magnetic resonance diffusion sequence spectrum of a 20 mM deuterated chloroform solution of compound A4 showed that it could form a supramolecular polymer with a molecular weight of ∼100,000 through multiple hydrogen bonding interactions of ureidopyrimidone units. The structural formula of compound A4 is shown below.

[0100]

[0101] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. An aromatic oligoamide folded body with a protected aminoalkoxy side chain, characterized in that: The aromatic oligoamide folded body has the following structure: R' in each repeating unit is independently selected from linear alkyl, branched alkyl and Where m = 0 to 2, and Appears at least once; R" is selected from the group consisting of linear alkyl, branched alkyl and n=1 to 8.

2. The aromatic oligoamide folded product with protected aminoalkoxy side chains according to claim 1, characterized in that: The R' in each repeating unit is independently selected from propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, isopentyl and Where m = 0 to 2, and Occurs at least once.

3. The aromatic oligoamide folded product with protected aminoalkoxy side chains according to claim 1, characterized in that: wherein R" is selected from propyl, isopropyl, butyl, isobutyl, tert-butyl and 4. The aromatic oligoamide folded product with protected aminoalkoxy side chains according to claim 1, characterized in that: The aromatic oligoamide folded body comprises compound A1, A2 or A3, wherein the structural formula of A1 is: The structural formula of A2 is: The structural formula of A3 is:

5. A method for preparing an aromatic oligoamide folded product with protected aminoalkoxy side chains as claimed in any one of claims 1 to 4, characterized in that: When the aromatic oligoamide folded body is compound A1, the preparation process includes the following steps: using compound 7 as a starting material, first reacting it with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, and then reacting the acyl chloride residue with a mixture of diisopropylethylamine and compound 8 to obtain compound A1. The reaction process is shown below: The structural formula of compound 8 is 6. A method for preparing an aromatic oligoamide folded product with protected aminoalkoxy side chains as claimed in any one of claims 1 to 4, characterized in that: When the aromatic oligoamide folded body is compound A2, the preparation process includes the following steps: using compound 3 as a raw material, first reacting it with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, and then reacting the acyl chloride residue with a mixture of diisopropylethylamine and compound 9 to obtain compound A2. The reaction process is shown below: The structural formula of compound 3 is The structural formula of compound 9 is 7. The method for preparing an aromatic oligoamide folded body with a protected aminoalkoxy side chain according to claim 6, characterized in that: The specific preparation process of compound 3 is as follows: Compound 1 is used as a raw material, reacted with diisopropylethylamine and isopropyl chloroformate in an organic solvent to obtain compound 2, and compound 2 is reacted with tetrahydrofuran and sodium hydroxide to obtain compound 3. The reaction process is as follows:

8. A method for preparing an aromatic oligoamide folded product with protected aminoalkoxy side chains as claimed in any one of claims 1 to 4, characterized in that: When the aromatic oligoamide folded body is compound A3, the preparation process includes the following steps: using compound 6 as a raw material, first reacting it with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, and then reacting the acyl chloride residue with a mixture of diisopropylethylamine and compound 10 to obtain compound A3. The reaction process is shown below: The structural formula of compound 6 is The structural formula of compound 10 is 9. The method for preparing an aromatic oligoamide folded body with a protected aminoalkoxy side chain according to claim 8, characterized in that: The specific preparation process of compound 6 is as follows: Compound 3 is used as a raw material, reacted with 1-chloro-N,N,2-trimethylpropyleneamine in an organic solvent to obtain an acyl chloride residue, the acyl chloride residue is reacted with compound 4 and diisopropylethylamine to obtain compound 5, and compound 5 is reacted with lithium hydroxide monohydrate added to tetrahydrofuran solution to obtain compound 6. The reaction process is as follows:

10. Use of an aromatic oligoamide folded product with protected aminoalkoxy side chains as claimed in any one of claims 1 to 4, characterized in that: The aromatic oligoamide foldamer is used to construct a supramolecular secondary assembly system.

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