A Switchable Helical Capsule for Encapsulation and Release of

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A Switchable Helical Capsule for Encapsulation and Release of Potassium Ion Wei Wang, Chenyang Zhang, Shuaiwei Qi, Xiaoli Deng, Bing Yang, Junqiu Liu, and Zeyuan Dong J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02840 • Publication Date (Web): 25 Jan 2018 Downloaded from http://pubs.acs.org on January 29, 2018

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The Journal of Organic Chemistry

A Switchable Helical Capsule for Encapsulation and Release of Potassium Ion Wei Wang, Chenyang Zhang, Shuaiwei Qi, Xiaoli Deng, Bing Yang, Junqiu Liu, Zeyuan Dong* State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012 (P.R. China) Supporting Information

ABSTRACT: A type of aromatic helical capsules was synthesized. The crystal structure proved an inner cavity that could perform switchable encapsulation and release of potassium ion through protonation/deprotonation-mediated extension and contraction of molecular motion.

■ INTRODUCTION Helix is a key structural motif of biomacromolecules like DNA and proteins and plays important roles in performing their biological functions, such as molecular recognition, molecular programming, and catalysis.1-6 Recently considerable efforts had been devoted to design synthetic helices so as to expand their applications in different areas including molecular receptors,7-14 ion channels,15,16 chemical sensors,17,18 catalysts19 and stimuliresponsive materials.20-23 Predictable folding of specific structural sequences has allowed one to create synthetic receptors with a functional cavity for specifically binding guest molecules.2 For instance, Huc and coworkers have developed a series of helical capsules with modular cavities for encapsulating neutral guest molecules including fructose, tartaric acid, malic acid, and citric acid and so on.24 Although helix-based receptors for recognizing ions have been prepared in the past,25-27 these helical receptors actually have an induced cavity owing to the ion-assisted folding. However, it is rather difficult to design a helical capsule with biomimetic functions of natural receptors that can perform the encapsulation and release of guest molecules under physiological environment. Helical capsules can not only position functional groups inside the binding cavity but also provide dynamic feature in the folding structures. As expected, folding and unfolding of helical capsules will give rise to the emergence and disappearance of the cavities, thus possibly achieving the encapsulation and release of guests, which

makes for a stimuli-responsive acceptor. Helices have been used to design responsive materials owing to their reversible folding in the dynamic structures.28,29 Taking the folding and unfolding of helical structure into accounts, stimuli-responsive helical capsules could be rationally designed. However, it remains challenging to create such a helical capsule that could be reversibly adjusted by external stimuli, e.g., metal coordination30 and pH 31-33 . Herein, we reported a type of aromatic helical oligomers that displayed reversible structural conversion between helical and extended conformations via the protonation/deprotonation of central pyridine group in the structural sequence, thus allowing ion capture and release. Such a stimuli-responsive acceptor is useful for the design of ion-related transmembrane transporters and channels.

■ RESULTS AND DISCUSSION We previously introduced an efficient approach to prepare pore-containing helical polymers.34 According to the reported method with minor modification, a new type of aromatic helical oligomers (Scheme 1) was synthesized and fully characterized (see Supporting Information). These aromatic helical oligomers possess a rigid scaffold with a binding cavity. For example, pentamer 1 possesses a cavity but just one helical turn. In order to generate a helical capsule, heptamer 2a was then tailored by capping two quinoline groups at the terminals of pentamer.2,11 Solid state studies were carried out and fully supported this tailor. The crystal grew upon diffusion of n-hexane into a

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chloroform solution and thus was analyzed by X-ray diffraction. Single crystal structure of heptamer 2a proved a helical capsule conformation with a specific cavity (Figure 1). Heptamer 2a possesses two helical turns with a central cavity diameter of ca. 0.6 nm and two quinolone capping groups.

Scheme 1. Synthetic procedure of helical capsules 1 and 2. Reaction conditions: (i) PyBop, DMF, TEA, 80%; (ii) CCl4, PPh3, CHCl3, 80℃, 75%; (iii) PyBop, DMF, TEA, 81%; (iv) CCl4, PPh3, CHCl3, 80℃, 64%; (v) NH4VO3, HCOONH4, Pd/C, CH2Cl2, CH3OH, 91%; (vi) (1S, 4R)-Camphanoyl chloride, TEA, CHCl3, 67%.

Figure 1. Single crystal structure of 2a (left, the green ball denotes the inner cavity) and its partial structures (right). Isobutoxy groups and solvent molecules are not shown for clarity.

We wondered if the helical structures could be adjusted via protonation/deprotonation treatment. Pentamer 1 was thus investigated by 1H NMR spectrum to observe the reversible structural conversion between helical and extended conformations (Figure 2). The protonation of central pyridine group of 1 was detectable in the presence of TFA (10 equiv.), as evidences that a new proton peak (12.6 ppm) appeared and the proton integration gave approximate 1 (Figure S1). Moreover, the aromatic proton signals of 1 are dramatically shifted to downfield in the presence of TFA, suggesting a structural conversion after protonation.28 The protonated 1+ will give rise to an extended conformation with the loss of a cavity. However, when excess amount of TEA was added, the NMR signals of 1 returned back. This observation indicated that the helical structure can be reversibly adjusted via protonation/deprotonation process. Besides, UV-Vis titration experiments of the protonation of 1 were performed (Figure S2). The increasing absorbance and red shift effect was observed both in 225 nm and 330 nm, and the decreasing absorbance in 270 nm. This phenomenon is consistent with the proposed transition from the helical conformation to the unfolded strand

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for 1+.28 Likewise, the reversibility of heptamer 2a was confirmed during the protonation and deprotonation process by 1H NMR tests (Figure S3). As shown (Figure S3b), the remarkable downfield shift of aromatic proton signals of 2a by adding TFA revealed a transformation from helical to outstretched conformation. The addition of excess amount of TEA makes 2a+ come back to the helically folding state (Figure S3c). Our results clearly demonstrated a reversible transformation of heptamer 2a from helical to extended conformation.

1

+

Figure 2. Partial H NMR spectra of (a): 1 (0.015 M); (b): 1 (added 10 equiv. TFA in 1) and (c): deprotonation (added 10 + equiv. TEA in 1 ) in CDCl3, the ＊ (CDCl3) and ● (TFA) represent the solvent peek.

Circular dichroism (CD) measurements were performed to corroborate the reversible process. Chiral 2b covalently induced by (S)-(-)-camphanoyl group shows a strong band in 240, 270, 340 and 380 nm in CD spectrum, as shown in Figure 3a, which was indicative of the helical conformation in solution. However, with the addition of TFA the CD intensity of 2b gradually decreased, suggesting that the helical conformation was collapsed through protonation treatment. Notably, the CD intensity of protonated 2b did not completely disappear. This result implied that only the central pyridine group of 2b was protonated, because the chiral induced quinoline dimer can still show the weak CD singals.35 Furthermore, the addition of TEA made the signals of 2b recover (Figure 3b).


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The Journal of Organic Chemistry Figure 3. CD spectra of (a): treated by 0, 1, 4, 8, 10, 20, 40, 60, 80 and 100 equiv. of TFA respectively in 2b to testify the unfolding process by protonation; (b): treated by 40 equiv. of + TEA in 2b (40 eq. TFA) to testify the refolded process by deprotonation. UV-Vis titration experiments of (c): 2a (0.12 µM) in acetonitrile with the addition of different amounts of + + + K ; (d) 2a (0.12 µM) for binding to K .

The crystal structure of heptamer 2a showed a binding cavity for potassium ion. Since potassium ion plays important physiological functions, such as signal pathway involved in natural potassium channels, artificial potassium acceptors are possible to mimic the functions as transmembrane transporters or channels.15,16 UV-Vis titrations indicated that pentamer 1 showed very low affinity for K+ (Figure S4). However, the long heptamer 2a can strongly bind K+, as observed by MALDI-TOF (Figure S5) and UV-Vis titrations (see Figure 3c). Job’s plots from UVVis titration experiments indicated that heptamer 2a binds K+ to form the 1:1 inclusion complex (Figure 4b).

model, the associate constant (Ka) was calculated to be 3200±230 M-1 (Figure S6), which is consistent with the result from the Hildebrand and Benesi equation. Potassium ion capture and release of heptamer 2a was investigated by UV-Vis titrations and NMR spectra. The 1:1 complex of heptamer 2a and K+ can be collapsed while adding TFA. The protonated 2a+ lost the binding ability for K+, as evidenced that the absorbance intensity in UVVis titrations did not change with the increase of potassium concentration (Figure 3d). However, after deprotonation by adding TEA, the protonated 2a folded again to the helical capsule. As expected, the ability of potassium capture recovered (Figure s7). 1H NMR spectra provided further supports on the reversible binding process in the presence of KPF6. The aromatic proton signals of 2a were shifted to upfield owing to the inclusion complexation of K+, whereas those of protonated 2a remained unchanged in the presence of K+ (Figures s8 and s9). The repeatability of the binding and release of potassium ion was monitored by UV-Vis spectra (Figure s10). The repeatability was realized owing to the stability of helical structure. These observations clearly indicated that the helical capsule 2a enables to encapsulate and release K+ by external stimuli.

■ CONCLUSION

Figure 4. (a) UV-vis spectra of titration experiments of 2a -4 (1.2×10 M) in acetonitrile with the addition of different + amount of K ; Inset: measurement of the binding constant of -4 2a (1.2×10 M) in acetonitrile at 270 nm. (b) Job’s plot experiments to study the binding ratio between 2a and K+ in acetonitrile at ambient temperature.

With the result of Job’s plot by a 1:1 stoichiometry, the inclusion complexation of K+ (G) with 2a (H) is expressed by the following equation:

In summary, we successfully synthesized a type of aromatic helical oligomers that displayed reversible structural conversion between helical and extended conformations via the protonation/deprotonation of central pyridine group in the structural sequence. The crystal structure of helical capsule was determined and demonstrated a unique adaptive feature of contraction-extension conversion for potassium ion encapsulation and release. Our study reported a new stimuli-responsive acceptor which is promising to apply in K+-related transmembrane transporters or channels.

■ EXPERIMENTAL SECTION We employed only the usual double reciprocal plot according to the modified Hildebrand and Benesi equation 1/△ △A = 1/Ka△ε[H][G] +1/△ △ε[H] H, G, Ka represents host (2a), guest (K+), binding constant, respectively. △A denotes the absorbance difference before and after guest molecules were added. △ε denotes the difference of the molar extinction coefficient between the host and host-guest complex at the same wavelength. The binding constant, Ka, was calculated for the curves of experimental measurements. The binding constant between 2a and K+ in the mixture solvent of acetonitrile and H2O (15: 1 by volume) solution was measured by monitoring the absorption at 270 nm. According to the double reciprocal plots based on the modified Hildebrand and Benesi equation,36 the binding constant between 2a and K+ was calculated to be 3500±480 M‒1 (Figure 4a). Based on the Fitplot for the UV-Vis titration of 2a with KPF6 at 270 nm using the 1:1

General Procedures. The commercially available reagents and solvents were used without further purification. All solvents were dried according to the standard procedures: tetrahydrofuran (THF) and triethylamine (TEA) were distilled from sodium, chloroform (CHCl3) and N,Ndimethylformamide (DMF) were distilled from calcium hydride (CaH2) prior. Reactions were monitored by thin layer chromatography (TLC) on Merck silica gel 60-F254 plates and observed under UV light, and column chromatography purifications were carried out using silica gel. Proton nuclear magnetic resonance (1H NMR) spectra and carbon nuclear magnetic resonance (13C NMR) spectra were recorded on the Bruker AVANCEIII 500. Chemical shifts for protons and carbon are referenced to solvent residual peak in the NMR solvent (CDCl3 = δ 7.26 ppm, DMSO = δ 2.50 ppm for 1H NMR spectrum; CDCl3 = δ 77.16 ppm, DMSO = δ 39.52 ppm for 13C NMR spectrum). NMR data are presented as follows: chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet). Mass spectra were reported on a HP1100EMD



(ESI), and Bruker MicrOTOF Q II (MALDI–TOF). The CD spectra were collected on a Jasco J-810 spectropolarimeter under a nitrogen atmosphere. UV-Visible spectra were recorded on a UV-2450 spectrophotometer. Synthesis. 4-Isobutoxy-N',N'-2,6-bis(4-isobutoxy-8-nit roquinoline-2-carbonyl)pyridine-2,6-dicarbohydrazide (5). To a solution of 4-isobutoxypyridine-2,6-dicarbo hydrazi de (3)37 (500 mg, 1.9 mmol) in dry DMF (5 mL) was added the hydrolytic quinoline monomer (4)38 (1.4 g, 4.8 mmol) and PyBop (2.1 g, 4 mmol). The reaction mixture was stirr ed at room temperature over night after added dry TEA (2 mL). Solvents were evaporated and the product was pour ed into 50 mL methanol overnight in 4 °C. The precipitate was collected by the filtration and washed with methanol to obtain crude product. And the residue was purified by flash chromatography (SiO2) eluting with dichloromethan e/ methanol (100:1, vol/vol) to obtain the compound 5 (1.2 g, yield 80%). 1H NMR (500 MHz, CDCl3) δ 10.67 (s, 2H), 1 0.01 (s, 2H), 8.13 (d, J = 8.2 Hz, 2H), 7.88 (d, J = 7.3 Hz, 2H), 7.60 (s, 2H), 7.55 (s, 2H), 7.43 (t, J = 7.8 Hz, 2H), 4.11 (d, J = 6.4 Hz, 4H), 3.86 (d, J = 6.4 Hz, 2H), 2.29 (dd, J = 13.1, 6. 6 Hz, 3H), 1.19 – 1.03 (m, 18H). 5,5'-(4-isobutoxypyridine-2,6-diyl)bis(2-(4-isobutoxy-8nitroquinolin-2-yl)-1,3,4-oxadiazole) (1). 5 (1 g, 1.23 mmol) was dissolved in dry chloroform (5 mL) in a 100 mL flask, and triphenylphosphine (1.3 g, 4.9 mmol) and tetrachloro methane (0.7 g, 4.5 mmol) was added. And then the reacti on mixture was refluxed at 80 °C for 4h. Solvents were eva porated and the crude product was purified by flash chro matography (SiO2) eluting with dichloromethane/ metha nol (150:1, vol/vol) to obtain 1 as a pale yellow solid (0.72 g , yield 75%). 1H NMR (500 MHz, CDCl3) δ 8.52 (dd, J = 8.4, 1.2 Hz, 2H), 8.13 (dd, J = 7.5, 1.2 Hz, 2H), 8.00 (s, 2H), 7.91 (s, 2H), 7.72 – 7.64 (m, 2H), 4.21 (d, J = 6.4 Hz, 4H), 4.07 (d, J = 6.4 Hz, 2H), 2.35 (td, J = 13.2, 6.6 Hz, 2H), 2.27 (dt, J = 13.3, 6.6 Hz, 1H), 1.16 (dd, J = 13.2, 6.7 Hz, 19H). 13C NMR (500 MHz, CDCl3) δ 167.1, 164.8, 164.5, 162.8, 148.2, 146.2, 1 45.4, 140.4, 126.4, 125.8, 125.3, 123.1, 112.6, 101.3, 76.0, 75.7, 2 8.2, 28.1, 19.2, 19.1. HRMS (ESI-TOF) m/z: [M+H]+ calcd fo r C39H38N9O9 776.2714; Found 776.2763. N,N'-(2,2'-(2,2'-(4-isobutoxypyridine-2,6-dicarbonyl)bis(h ydrazinecarbonyl))bis(4-isobutoxyquinoline-8,2-diyl))bis (4-isobutoxy-8-nitroquinoline-2-carboxamide) (2d). To a solution of 3 (500 mg, 1.9 mmol) in dry DMF (5 mL) was a dded the hydrolytic quinoline dimer (6)38 (2.5 g, 4.7 mmol ) and PyBop (2.1 g, 4 mmol). The reaction mixture was stir red at room temperature over night after added dry TEA ( 2 mL). Solvents were evaporated and the product was pou red into 50 mL methanol overnight in 4 °C. The precipitat e was collected by the filtration and washed with methan ol to obtain crude product. And the residue was purified b y flash chromatography (SiO2) eluting with dichlorometh ane/ methanol (50:1, vol/vol) to obtain 2d (1.96g, yield 81 %) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ 11.6 8 (s, 2H), 10.48 (s, 2H), 9.90 (s, 2H), 9.20 (d, J = 7.6 Hz, 2 H), 8.41 (d, J = 7.5 Hz, 2H), 8.35 (d, J = 8.2 Hz, 2H), 8.05 (d, J = 8.2 Hz, 2H), 7.91 (s, 2H), 7.85 (s, 2H), 7.65 (t, J = 8.0 H

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z, 2H), 7.40 (t, J = 7.9 Hz, 2H), 4.12 (d, J = 6.4 Hz, 8H), 3.95 (d, J = 6.6 Hz, 2H), 2.29 (dt, J = 13.2, 6.6 Hz, 4H), 2.17 (dt, J = 13.2, 6.8 Hz, 1H), 1.13 (d, J = 6.7 Hz, 21H), 1.06 (d, J = 6.7 Hz, 6H). 13C NMR (500 MHz, CDCl3) δ 163.1, 162.5, 162.1, 15 0.0, 149.8, 147.1, 138.8, 134.3, 127.5, 126.6, 125.6, 123.0, 122.5, 1 18.8, 116.9, 111.8, 100.3, 99.9, 75.7, 75.2, 28.1, 28.1, 19.2, 19.1, 1 9.1; HRMS (MALDI-TOF) m/z: [M+H]+ calcd for C67H70N13 O15 1296.5036; Found 1296.5951. N,N'-(2,2'-(5,5'-(4-isobutoxypyridine-2,6-diyl)bis(1,3,4-ox adi -azole-5,2-diyl))bis(4-isobutoxyquinoline-8,2-diyl))bis (4-isob -utoxy-8-nitroquinoline-2-carboxamide) (2a). To a solution of 2d (1 g, 0.7 mmol) in dry dichloromethane (10 mL) was added triphenylphosphine (1.8 g, 6.9 mmol) and tetrachloromethane (0.7 g, 4.5 mmol), and the reaction m ixture was refluxed at 80 °C for 4h. Solvents were evaporat ed and the crude product was purified by flash chromatog raphy (SiO2) eluting with dichloromethane/ methanol (20 0:1, vol/vol) to obtain 2a as a pale yellow solid (0.62 g, yiel d 64%). 1H NMR (600 MHz, CDCl3) δ 11.91 (s, 2H), 9.13 (d, J = 6.9 Hz, 2H), 8.13 (s, 2H), 8.00 (d, J = 7.4 Hz, 2H), 7.97 ( d, J = 7.2 Hz, 2H), 7.86 (dd, J = 7.4, 1.2 Hz, 2H), 7.73 (t, J = 7.9 Hz, 2H), 7.59 (s, 2H), 7.26 (t, 2H), 6.98 (s, 2H), 4.15 (d, J = 6.4 Hz, 4H), 4.11 (d, J = 6.4 Hz, 2H), 3.16 (d, J = 6.8 Hz, 4H), 2.38 (dt, J = 13.4, 6.7 Hz, 2H), 2.28 (dt, J = 13.2, 6.6 Hz, 1H), 2.02 (dt, J = 13.6, 6.8 Hz, 2H), 1.24 (d, J = 6.7 Hz, 12H), 1.18 (d, J = 6.7 Hz, 6H), 1.00 (d, J = 6.7 Hz, 12H). 13C NMR ( 500 MHz, CDCl3) δ 166.4, 164.7, 164.5, 162.4, 162.2, 162.1, 15 3.2, 145.3, 145.1, 141.9, 139.7, 139.5, 135.5, 128.1, 127.1, 126.2, 12 4.8, 123.0, 121.5, 117.8, 115.8, 111.9, 99.6, 98.7, 75.5, 75.3, 75.0, 28.3, 28.3, 27.7, 19.3, 19.2, 19.0. MS (MALDI–TOF) m/z: [M +Na]+ calcd for C67H65N13O13Na 1282.48; Found 1282.51. N,N'-(2,2'-(5,5'-(4-isobutoxypyridine-2,6-diyl)bis(1,3,4-ox adi-azole-5,2-diyl))bis(4-isobutoxyquinoline-8,2-diyl))bis (8-amino-4-isobutoxyquinoline-2-carboxamide) (2e). To a solution of 2a (0.126 g, 0.1 mmol) in dichloromethane was added ammonium formate (0.04 g, 0.3 mmol), Pa/C (0.01 3 g) and ammonium metavanadate (0.07 g, 1.1 mmol) in m ethanol at ambient temperature and stirred overnight. Th e precipitate was removed by the filtration, and the super natant was concentrated under the reduced pressure. 50 mL dichloromethane was added to the mixture and then washed with water to remove salts. The organic phase was collected and dried with Na2SO4. The solvent was remove d under reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane/ methanol= 50/1, v/v) to obtain yellow product (0.11 g, yiel d 91%). 1H NMR (500 MHz, DMSO) δ 11.73 (s, 2H), 8.99 (d, J = 7.3 Hz, 2H), 8.09 (s, 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H), 7.43 (s, 2H), 6. 90 – 6.81 (m, 2H), 6.71 – 6.64 (m, 2H), 6.12 (d, J = 7.1 Hz, 2 H), 5.47 (s, 4H), 4.36 – 4.00 (m, 9H), 2.34 – 2.27 (m, 2H), 2. 24 – 2.18 (m, 1H), 2.09 – 1.99 (m, 2H), 1.20 (d, J = 6.6 Hz, 12 H), 1.14 (d, J = 6.6 Hz, 6H), 1.03 (d, J = 6.5 Hz, 12H). HRMS (ESI-TOF) m/z: [M+H]+ calcd for C67H70N13O9 1200.5341; F ound 1200.5399. N,N'-(2,2'-(5,5'-(4-isobutoxypyridine-2,6-diyl)bis(1,3,4-ox adi-azole-5,2-diyl))bis(4-isobutoxyquinoline-8,2-diyl))bis


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The Journal of Organic Chemistry (4-iso-butoxy-8-(4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1] heptane-1-carboxamido)quinoline-2-carboxamide) (2b). T he generated product 2e (100 mg, 0.08 mmol) was dissolv ed in dry chloroform (2 mL) in a 50 mL flask, and then (-) -(1S, 4R)-Camphanoyl Chloride (100 mg, 4.6 mmol) and T EA (2 mL) was added. The mixture was stirred at room te mperature for 4h and concentrated under the reduced pre ssure. The resulting mixture was poured into 30 mL meth anol overnight in 4 °C. The precipitate was collected by th e filtration and washed with methanol to obtain crude pro duct. The crude product was purified by silica gel column chromatography using methanol and dichloromethane as eluent (methanol/dichloromethane = 1/70 to 1:100, v/v) to afford the product 2b (87 mg, yield 67%). 1H NMR (500 M Hz, CDCl3) δ 11.71 (s, 2H), 10.01 (s, 2H), 9.05 (d, J = 7.6 Hz, 2H), 8.14 (d, J = 7.5 Hz, 2H), 8.10 (s, 2H), 8.02 (d, J = 8.2 H z, 2H), 7.70 (t, J = 7.9 Hz, 2H), 7.62 (s, 2H), 7.33 (d, J = 8.2 Hz, 2H), 7.07 (t, J = 7.9 Hz, 2H), 6.86 (s, 2H), 4.30 – 4.24 (m, 2H), 4.18 – 4.14 (m, 2H), 4.11 (d, J = 7.5 Hz, 1H), 4.00 – 3.96 (m, 1H), 3.07 (t, J = 8.9 Hz, 2H), 2.85 – 2.78 (m, 2H), 2. 40 (dt, J = 13.3, 6.6 Hz, 2H), 2.32 – 2.24 (m, 1H), 2.15 – 2.07 (m, 2H), 2.05 – 1.97 (m, 2H), 1.56 (s, 6H), 1.42 (d, J = 7.1 Hz, 2H), 1.30 (d, J = 6.7 Hz, 6H), 1.28 – 1.22 (m, 12H), 1.18 (d, J = 6.6 Hz, 6H), 0.95 (dd, J = 17.9, 6.7 Hz, 12H), 0.90 – 0.83 (m, 4H). 13C NMR (126 MHz, CDCl3) δ 176.4, 165.6, 164.9, 16 4.3, 162.6, 162.2, 162.1, 150.4, 145.2, 142.5, 139.4, 138.1, 135.2, 1 33.6, 127.6, 126.7, 121.5, 121.4, 116.8, 116.4, 116.0, 115.9, 111.7, 10 0.2, 98.4, 91.3, 75.3, 74.7, 54.3, 54.1, 28.7, 28.6, 28.5, 28.3, 27 .6, 19.5, 19.4, 19.3, 19.2, 18.7, 16.2, 16.2, 9.6. HRMS (ESI-TOF ) m/z: [M+H]+ calcd for C87H94N13O15 1560.6914; Found 156 0.6965.

■ ASSOCIATED CONTENT Supporting Information Figures giving NMR spectra for all compounds, tables, and CIF ﬁle of crystallographic data for 2a.

■ AUTHOR INFORMATION Corresponding Author * E-mail: [email protected].

Notes The authors declare no competing ﬁnancial interest.

■ ACKNOWLEDGMENT This work was supported by the Natural Science Foundation of China (No. 21574054, 21722403, 21420102007, and 21274051).

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