Total synthesis of breviscapin B via intramolecular dehydrative etherification

Abstract

The total synthesis of breviscapin B, a norlignan natural product having an unusual 2,2-diaryltetrahydrofuran skeleton, has been achieved via intramolecular dehydrative Williamson ether synthesis as a key step. The use of a combination of p-TsOH·H₂O and polyfluorinated alcohol was found as an effective method for the synthesis of 2-aryl-substituted saturated oxygen heterocycles.

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Introduction

Breviscapin B (1) is a norlignan natural product that was isolated by the research group of Li and Wang in 2010 from the rhizomes of Curculigo breviscapa, one of the rich sources of norlignan natural products (Fig. 1).¹ Structurally, 1 is characterized by a rare and unique 2,2-diaryltetrahydrofuran skeleton and is closely related to sacidumlignan D (2)² and gymnothespirolignans A–F (3a–3f),³ which show a variety of biological activities. While breviscapin B (1) exhibited only weak neuroprotective effects on corticosterone-treated neuroblastoma cells SH-SY5Y by inhibiting the endoplasmic reticulum stress-mitochondria pathway,⁴ other bioactivities of 1 have not been further evaluated probably due to the low natural abundance (0.001%, 14 mg out of 1.3 kg of the air-dried and powdered rhizomes of Curculigo breviscapa). Despite its attractive architectures and potential for other bioactivities, there have been no reports on synthetic studies of this natural product.

Fig. 1 Structures of natural products bearing a 2,2-diaryltetra hydrofuran skeleton.

We have recently reported Brønsted acid-catalyzed intramolecular Friedel–Crafts reactions⁵ and dehydrative cyanation⁶ of benzylic alcohols, in which the use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent, which would effectively stabilize the carbocation intermediate,⁷ is critical for efficient cyclization.

As an extension of our study in this area, we envisioned that a 2,2-diaryltetrahydrofuran skeleton could be constructed through an intramolecular dehydrative Williamson ether synthesis.⁸ We herein report our effort in this area, which resulted in the first total synthesis of breviscapin B (1).

Results and discussion

Our synthetic strategy for 1 is outlined retrosynthetically in Scheme 1. As demonstrated in the synthesis of sacidumlignan D and gymnothespirolignans B and C,^9,10 the 2,2-diaryltetrahydrofuran skeleton of 1 seems to be constructed from diol 4avia acid-catalyzed dehydrative etherification. It was anticipated that the diol 4 would be formed by a Grignard reaction of arylmetal species 5 with chiral lactone 6, which is easily accessible from the commercially available hydroxylactone 7. One concern for the synthetic strategy is, however, the feasibility of Williamson ether synthesis of 1,1-diarylbutane-1,4-diols with fewer electron-donating groups, because the synthesis of 1,1-diphenylbutane-1,4-diols by direct intramolecular dehydrative etherification requires harsher conditions¹¹ than those for the synthesis of sacidumlignan D and gymnothespirolignans B and C, in which synthesis of 2,2-diaryltetrahydrofuran motifs could be easily achieved by reduction of γ-lactones such as 8 bearing trialkoxy-substituted electron-rich benzene rings with LiAlH₄ followed by treatment of 1,1-diarylbutane-1,4-diols with trifluoroacetic acid in dichloromethane.^10a

Scheme 1 Synthetic plan for breviscapin B and acid-catalyzed construction of 2,2-diaryltetrahydrofuran in the synthesis of sacidumlignan D.

In this context, we initially explored the cyclization of 1,1-diphenylbutane-1,5-diol (11a) as a model compound (Table 1). To our delight, the reaction in the presence of 1 mol% of p-TsOH·H₂O in HFIP proceeded smoothly at 25 °C to completion within 0.25 h to give 2,2-diphenyltetrahydrofuran (12a) in 94% yield along with small amount (5%) of 4,4-diphenylbut-3-en-1-ol (13a)^12,13 (entry 1). A solvent survey in the presence of p-TsOH·H₂O as a catalyst revealed that the use of dichloromethane, toluene, and nitromethane required larger loading of p-TsOH·H₂O (10 mol%), higher temperature (50 °C), and longer reaction times to complete the reaction as stated in previous reports (entries 2–4 vs. 1).^11,14 It is notable that the reaction in 2,2,2-trifluoroethnol (TFE) provided 12a in nearly quantitative yield with no trace of 13a, though there is no reasonable explanation for the advantage of TFE over HFIP in avoiding the formation of 13a (entry 5).¹⁵ No reaction took place in the absence of p-TsOH·H₂O in TFE, indicating that TFE itself does not have enough activity to promote the reaction (entry 6).^16,17 Using TFE as a reaction solvent, we next evaluated the ability of other Brønsted acids as catalysts. Trifluoroacetic acid as well as (±)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate ((±)-BINOL-PA) were found to be equally effective catalysts for this transformation, giving 12a in high yields (entries 7 and 8). Compared with previous intramolecular Williamson etherification of benzylic diols catalyzed by transition metal complexes,¹⁸ boron-based Lewis acids,¹⁹ and Brønsted acids,²⁰ the advantage of the present catalytic protocol is that the reaction can be conducted at room temperature with a lower catalyst loading without exclusion of air and moisture. As observed with intramolecular Friedel–Crafts alkenylation reaction of 1,5-diaryl-1-pentynes,^5a a high yield was achieved even in the presence of 10 equiv. of water (entry 9). Furthermore, gram-scale synthesis of 12a (1.05 g) could be achieved from 5 mmol of diol 11a as a starting material with 0.01 mol% of a catalyst (entry 10).

Table 1 Brønsted acid-catalyzed intramolecular dehydrative etherification of 1,1-diphenylbutane-1,4-diol (11a)^a

Entry	Catalyst	(Mol%)	Solvent	Temp (°C)	Time (h)	Yield^b (%)
a Unless otherwise noted, reactions were carried out as follows: Brønsted acid (1 mol%) was added to a solution of 11a (48.4 mg, 0.2 mmol) in the indicated solvent (2.0 mL) and the mixture was stirred at the indicated temperature. b Isolated yield. Values in parentheses correspond to the yield of 13a. c No reaction. d The reaction was performed in the presence of 10 equiv. of water. e The reaction was performed with 1.21 g (5 mmol) of 11a, giving 1.05 g of 12a.
1	p-TsOH·H2O	1	HFIP	25	0.25	94 (5)
2	p-TsOH·H2O	10	CH2Cl2	50	18	88 (9)
3	p-TsOH·H2O	10	Toluene	50	18	96 (3)
4	p-TsOH·H2O	10	CH3NO2	50	18	96 (3)
5	p-TsOH·H2O	1	TFE	25	0.25	98
6	—	—	TFE	25	24	—^c
7	CF3CO2H	1	TFE	25	0.5	96
8	(±)-BINOL-PA	1	TFE	25	0.25	95
9^d	p-TsOH·H2O	1	TFE	25	0.25	98
10^e	p-TsOH·H2O	0.01	TFE	25	1.5	95

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With optimized reaction conditions in hand, we then investigated the substrate scope of the present intramolecular dehydrative etherification of various diols, and the results are summarized in Scheme 2. As expected from the reaction mechanism based on the formation of the benzylic carbocation intermediate, the reaction of diols 11b and 11c possessing an electron-rich aromatic rings proceeded smoothly to provide the corresponding 2,2-diaryltetrahydrofurans 12b and 12c in excellent yields. Even diol 11d bearing a strong electron-withdrawing trifluoromethyl group was also found to be a substrate for the present cyclization reaction to give 12d in moderate yield (21%). It was found that a secondary alcohol was also an effective nucleophile, giving 2,2,5-trisubstituted tetrahydrofuran 12e in 93% yield. In addition, not only one aryl-substituted benzylic tertiary alcohol 11f but also secondary benzyl alcohols 11g–11l worked well to give 2-aryltetrahydrofurans 12f–12l in good to high yields. Tetrahydropyrans 12m–12q could be obtained via the cyclization of 1-arylpentane-1,5-diols 11m–11q under the optimized reaction conditions.

Scheme 2 Substrate scope.

Moreover, the present catalytic protocol was found to be applicable to the cyclization of 1,2-phenylene-tethered diols 11r–11t for the construction of benzo-fused oxygen heterocycles such as 1-substituted 1,3-dihydroisobenzofurans 12r–12s and 2-phenylchromane (12t) in high yields (Scheme 3).

Scheme 3 Synthesis of dihydroisobenzofuran and chromane derivatives via intramolecular dehydrative etherification.

Encouraged by these positive results, we then turned our attention to the total synthesis of breviscapin B (1) to prove the synthetic utility of the present catalytic cyclization method (Scheme 4). To this end, methoxymethylation of the hydroxy group of commercially available chiral lactone (S)-7 followed by Grignard reaction using arylmagnesium bromide 5 gave diol 4 in 64% overall yield. While treatment of diol 4 in the presence of 1 mol% of p-TsOH·H₂O in TFE led to the formation of a complex mixture of products probably due to the competition of the deprotection of methoxymethyl ethers,⁵ we were pleased to find that the reaction with the use of HFIP proceeded smoothly at 25 °C to completion within 0.1 h to provide 5,5-diaryl-subsituted tetrahydrofuran derivative 14 in 95% yield. Finally, treatment of 14 with 10 mol% of p-TsOH·H₂O in TFE²¹ at 25 °C for 16 h completed the first total synthesis of breviscapin B (1) in 40% yield with [α]²⁰_D −7.07 (c 0.52, MeOH), in good agreement with the literature value [lit.,¹ [α]²⁷_D −7.1 (c 0.22, MeOH)]. Thus, the absolute configuration of natural 1 has been identified as S.

Scheme 4 Synthesis of breviscapin B.

Conclusions

In summary, we have accomplished the first total synthesis and determination of the absolute configuration of breviscapin B (1) in 4 steps from the commercially available chiral γ-lactone (S)-7 with 22.3% overall yield. Key features of the synthesis include a Brønsted acid-catalyzed intramolecular dehydrative etherification of 1-arylbutane-1,4-diols or 1-arylpentane-1,5-diols using p-TsOH·H₂O as a catalyst and polyfluorinated alcohol as a solvent. This operationally simple, transition metal-free catalytic process using inexpensive and readily available p-TsOH·H₂O requires no exclusion of air and moisture and can be conducted under open-flask conditions. In addition, it was found that the present catalytic protocol is applicable to a variety of benzylic diols possessing fewer electron-donating groups on the benzene ring. Further efforts directed at the synthesis of bioactive natural and nonnatural products bearing 2-aryl-substituted oxygen heterocycles are currently in progress.

Experimental section

General methods

Melting points were recorded on a Yamato melting point apparatus model MP-500P and were uncorrected. Optical rotations were measured using a JASCO P1020 digital polarimeter at the sodium D line (589 nm). IR spectra were recorded on a JASCO FT/IR-5300 spectrometer and absorbance bands are reported in wavenumber (cm⁻¹). ¹H NMR spectra were recorded on JEOL ECZ-500 (500 MHz) spectrometer or chemical shifts are reported relative to internal standard (tetramethylsilane; δ_H 0.00, CDCl₃; δ_H 7.26, CD₃OD; δ_H 3.31). Data are presented as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, sext = sextet, sept = septet, hept = heptet, m = multiplet, br = broad), coupling constant and integration. ¹³C {¹H} NMR spectra were recorded on JEOL ECZ-500 (150 MHz) spectrometer. The following internal references were used: CDCl₃ (δ 77.03) CD₃OD (δ 49.00). Infrared (IR) spectra were recorded on a JASCO FT/IR-4100. High-resolution mass spectra (HRMS) were recorded on JEOL AccuTOF and Waters Xevo G2-S QTOF system. Flash column chromatography was performed with YAMAZEN EPCLC-W-Prep 2XY equipped with YAMAZEN Universal Column Premium or CHROMATOREX Q-Pack columns. Analytical thin layer chromatography (TLC) was carried out on Merck Kieselgel 60 F254 plates with visualization by ultraviolet, anisaldehyde stain solution or phosphomolybdic acid stain solution. All non-aqueous reactions were carried out in flame-dried glassware under argon atmosphere unless otherwise noted. Reagents and solvents were purified by standard means.

Representative procedure for the intramolecular dehydrative etherification of 1,1-diphenylbutane-1,4-diol (entry 5 in Table 1)

2,2-Diphenyltetrahydrofuran (12a)²². A solution of p-TsOH·H₂O (0.38 mg, 0.002 mmol) in 2,2,2-trifluoroethanol (0.1 mL) was added to a stirred solution of 11a (48.5 mg, 0.2 mmol) in 2,2,2-trifluoroethanol (2 mL) at 25 °C. The mixture was stirred at the same temperature for 0.25 h and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 1 : 0 → 1 : 1 hexane/CH₂Cl₂) to afford 12a (43.7 mg, 98%) as a white solid; TLC R_f = 0.20 (4 : 1 hexane/CH₂Cl₂); mp 72.0–73.0 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.43 (d, J = 7.5 Hz, 4H), 7.28 (dd, J = 7.5, 7.5 Hz, 4H), 7.20–7.17 (m, 2H), 4.05 (t, J = 7.5 Hz, 2H), 2.56 (t, J = 7.5 Hz, 2H), 1.94 (quint, J = 7.5 Hz, 2H); ¹³C {¹H} NMR (125 MHz, CDCl₃) δ 146.5, 128.3, 126.8, 126.0, 88.2, 67.5, 38.7, 25.6.

Synthesis of breviscapin B

(S)-5-[(Methoxymethoxy)methyl]dihydrofuran-2(3H)-one (6). Chloromethyl methyl ether (1.4 g, 1.3 mL, 17.2 mmol) was added to a stirred of (S)-(+)-dihydro-5-(hydroxymethyl)-2(3H)-furanone (1.0 g, 0.82 mL, 8.6 mmol), N,N-diisopropylethylamine (3.3 g, 4.4 mL, 25 mmol) in CH₂Cl₂ (50 mL) at 0 °C and the mixture was stirred under reflux for 12 h. The reaction was quenched with saturated aqueous NH₄Cl solution (10 mL) at room temperature and the whole mixture was extracted with Et₂O (3 × 10 mL). The combined organic extracts were washed with H₂O (2 × 10 mL) and brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 4 : 1 → 1 : 1 hexane/Et₂O) to afford 6 (1.04 g, 75%) as a colorless oil; TLC R_f = 0.25 (100% Et₂O); [α]²⁰_D = +28.3° (c 1.28, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 4.72–4.67 (m, 1H), 4.65 (s, 2H), 3.77 (dd, J = 10.9, 3.4 Hz, 1H), 3.65 (dd, J = 10.9, 4.6 Hz, 1H), 3.37 (s, 3H), 2.64 (ddd, J = 17.8, 10.3, 6.3 Hz, 1H), 2.50 (ddd, J = 17.2, 10.3, 7.5 Hz, 1H), 2.36–2.29 (m, 1H), 2.17–2.10 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃) δ 177.3, 96.8, 78.8, 69.1, 55.6, 28.5, 24.1; IR (ATR): 2938, 1769, 1460, 1418, 1348, 1275, 1146, 1115, 1071, 1037 cm⁻¹; HRMS (DART) m/z: [M + H]⁺ calcd for C₇H₁₃O₄ 161.0814; found 161.0816.

4-Bromo-1,2-bis(methoxymethoxy)benzene²³. Chloromethyl methyl ether (1.33 g, 1.24 mL, 16.5 mmol) was added to a stirred of 4-bromocatechol (1.04 g, 5.50 mmol), sodium hydride (60% in oil, 660 mg, 16.5 mmol) in N,N-dimethylformamide (10 mL) at 0 °C and the mixture was stirred at 25 °C for 1 h. The reaction was quenched with saturated aqueous NH₄Cl solution (10 mL) at room temperature and the whole mixture was extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with H₂O (2 × 10 mL) and brine (2 × 10 mL), dried over Na₂SO₄, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 1 : 0 → 2 : 1 hexane/EtOAc) to afford 4-bromo-1,2-bis(methoxymethoxy)benzene (1.50 g, 98%) as a colorless oil; TLC R_f = 0.28 (2 : 1 hexane/EtOAc); ¹H NMR (500 MHz, CDCl₃) δ 7.31 (d, J = 2.3 Hz, 1H), 7.08 (dd, J = 9.2, 2.3 Hz, 1H), 7.03 (d, J = 9.2 Hz, 1H), 5.21 (s, 2H), 5.20 (s, 2H), 3.52 (s, 3H), 3.50 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃) δ 148.2, 146.6, 125.4, 120.1, 118.2, 114.6, 95.6, 95.6, 56.5, 56.4.

(S)-1,1-Bis[3,4-bis(methoxymethoxy)phenyl]-5-(methoxymethoxy)pentane-1,4-diol (4). A solution of 4-bromo-1,2-bis(methoxymethoxy)benzene (723 mg, 2.6 mmol) in THF (5 mL) was added to a stirred mixture of magnesium turnings (127 mg, 5.2 mmol) and a few crystals of iodine in THF (20 mL) at 25 °C under argon. The mixture was stirred at 25 °C for 3 h. A solution of 6 (105 mg, 0.652 mmol) in THF (6 mL) was added and the mixture was stirred under reflux for 12 h. The reaction was quenched with saturated aqueous NH₄Cl solution (10 mL) at 0 °C and the whole mixture was extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with H₂O (10 mL) and brine (2 × 10 mL), dried over Na₂SO₄, filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 1 : 0 → 0 : 1 hexane/EtOAc) to afford 4 (307 mg, 85%) as a colorless oil; TLC R_f = 0.15 (100% Et₂O); [α]²⁵_D = +2.63° (c 2.18, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.27 (d, J = 2.3 Hz, 1H), 7.26 (d, J = 2.3 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.98 (dd, J = 8.6, 2.3 Hz, 1H), 6.97 (dd, J = 8.6, 2.3 Hz, 1H), 5.19 (s, 8H), 4.63–4.60 (m, 2H), 3.80–3.77 (m, 1H), 3.56 (dd, J = 10.3, 2.9 Hz, 1H), 3.50 (s, 3H), 3.49 (s, 3H), 3.48 (s, 6H), 3.47 (s, 1H), 3.37 (dd, J = 10.3, 7.5 Hz, 1H), 3.34 (s, 3H), 3.09 (d, J = 4.3 Hz, 1H), 2.44–2.34 (m, 2H), 1.55–1.43 (m, 2H); ¹³C {¹H} NMR (125 MHz, CDCl₃) δ 146.8, 146.8, 146.6, 146.6, 141.9, 141.7, 120.4, 120.3, 116.2, 116.2, 115.4, 115.3, 97.2, 95.8, 95.7, 95.5, 95.5, 77.4, 73.5, 71.0, 56.3, 56.2, 56.3, 56.2, 55.5, 38.4, 27.9; IR (ATR): 3420, 2922, 2826, 1587, 1505, 1443, 1424, 1396, 1252, 1206, 1150, 1124, 1071 cm⁻¹; HRMS (DART) m/z: [M + NH₄]⁺ calcd for C₂₇H₄₄NO₁₂ 574.2864; found 574.2852.

(S)-2,2-Bis[3,4-bis(methoxymethoxy)phenyl]-5-[(methoxymethoxy)methyl]tetrahydrofuran (14). A solution of p-TsOH·H₂O (0.38 mg, 0.002 mmol) in 1,1,1,3,3,3-hexafluoropropan-2-ol (0.1 mL) was added to a stirred solution of 4 (112 mg, 0.2 mmol) in 1,1,1,3,3,3-hexafluoropropan-2-ol (2 mL) at 25 °C. The mixture was stirred at the same temperature for 0.1 h. The reaction was quenched with saturated aqueous NaHCO₃ solution (10 mL) at room temperature and the whole mixture was extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with H₂O (10 mL) and brine (2 × 10 mL), dried over Na₂SO₄, filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 4 : 1 → 0 : 1 hexane/EtOAc) to afford 14 (102 mg, 95%) as a colorless oil; TLC R_f = 0.25 (1 : 1 hexane/EtOAc); [α]²⁵_D = +5.25° (c 1.01, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 7.29 (d, J = 2.3 Hz, 1H), 7.25 (d, J = 2.3 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 7.03 (d, J = 8.6 Hz, 1H), 7.10 (dd, J = 8.6, 2.3 Hz, 1H), 6.95 (dd, J = 8.6, 2.3 Hz, 1H), 5.22–5.17 (m, 8H), 4.69 (s, 2H), 4.35–4.31 (m, 1H), 3.67 (dd, J = 10.3, 5.7 Hz, 1H), 3.59 (dd, J = 10.3, 4.6 Hz, 1H), 3.50 (s, 6H), 3.49 (s, 3H), 3.49 (s, 3H), 3.38 (s, 3H), 2.61–2.56 (m, 1H), 2.48–2.42 (m, 1H), 2.03–1.96 (m, 1H), 1.82–1.76 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃) δ 146.9, 146.7, 146.2, 146.1, 141.4, 140.6, 120.1, 120.1, 116.3, 116.1, 115.1, 115.1, 96.8, 95.8, 95.7, 95.5, 88.2, 77.8, 70.8, 56.3, 56.3, 56.3, 56.2, 56.2, 55.3, 39.0, 28.5; IR (ATR): 2900, 2825, 1505, 1463, 1423, 1395, 1257, 1206, 1152, 1127, 1072, 1039 cm⁻¹; HRMS (DART) m/z: [M + H]⁺ calcd for C₂₇H₃₉O₁₁ 539.2492; found 539.2469.

(–)-Breviscapin B (1). A solution of p-TsOH·H₂O (0.8 mg, 0.0004 mmol) in 2,2,2-trifluoroethanol (0.1 mL) was added to a stirred solution of 14 (22 mg, 0.041 mmol) in 2,2,2-trifluoroethanol (1 mL) at 25 °C. The mixture was stirred at the same temperature for 16 h and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 1 : 0 → 6 : 4 CH₂Cl₂/MeOH) to afford the breviscapin B (1) (5.2 mg, 40%) a colorless oil; TLC R_f = 0.25 (4 : 1 CH₂Cl₂/MeOH); [α]²⁰_D = −7.07° (c 0.52, MeOH); ¹H NMR (500 MHz, CD₃OD) δ 6.84 (d, J = 2.3 Hz, 1H), 6.83 (d, J = 2.3 Hz, 1H), 6.73 (dd, J = 8.0, 2.3 Hz, 1H), 6.71 (dd, J = 8.6, 2.3 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.65 (d, J = 8.6 Hz, 1H), 4.16–4.11 (m, 1H), 3.62 (dd, J = 11.5, 5.7 Hz, 1H), 3.54 (dd, J = 11.5, 5.2 Hz, 1H), 2.54–2.49 (m, 1H), 2.38–2.33 (m, 1H), 1.97–1.90 (m, 1H), 1.78–1.72 (m, 1H); ¹³C {¹H} NMR (125 MHz, CD₃OD) δ 145.8, 145.6, 144.9, 144.9, 140.1, 139.3, 118.7, 118.6, 115.7, 115.6, 115.1, 114.8, 89.8, 80.4, 66.3, 39.5, 29.0; IR (ATR): 3274, 1630, 1517, 1436, 1371, 1282, 1254, 1200, 1116, 1048 cm⁻¹; HRMS (DART) m/z: [M + H]⁺ calcd for C₁₇H₁₉O₆ 319.1182; found 319.1167.

Author contributions

M. A. designed the experiments and supervised the project. K. M. and C. N. performed chemical synthesis and characterization of the compounds. S. S. assisted with experimental testing and data analysis. M. A. and K. M. wrote the manuscript and C. N. and S. S. reviewed and revised the manuscript. All of the authors have given approval to the final version of the manuscript.

Data availability

The authors confirm that the data supporting this article and the findings of this study have been included as part of the ESI.† The software used for drawing chemical structures is ChemDraw 21.0.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was partially supported by JSPS KAKENHI Grant JP21K06462 (M. A.) for Scientific Research (C). M. A. thanks Musashino University for the financial support.

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Footnote

† Electronic supplementary information (ESI) available: Experimental details and copies of spectra. See DOI: https://doi.org/10.1039/d5ob00350d

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