Efficient Synthesis and Bioactivity of Novel Triazole Derivatives

Abstract

Triazole pesticides are organic nitrogen-containing heterocyclic compounds, which contain 1,2,3-triazole ring. In order to develop potential glucosamine-6-phosphate synthase (GlmS) inhibitor fungicides, forty compounds of triazole derivatives were synthesized in an efficient way, thirty nine of them were new compounds. The structures of all the compounds were confirmed by high resolution mass spectrometer (HRMS), ¹H-NMR and ¹³C-NMR. The fungicidal activities results based on means of mycelium growth rate method indicated that some of the compounds exhibited good fungicidal activities against P. CapasiciLeonian, Sclerotinia sclerotiorum (Lib.) de Bary, Pyricularia oryzae Cav. and Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. at the concentration of 50 µg/mL, especially the inhibitory rates of compounds 1-d and 1-f were over 80%. At the same time, the preliminary studies based on the Elson-Morgan method indicated that the compounds exhibited some inhibitory activity toward glucosamine-6-phosphate synthase (GlmS). These compounds will be further studied as potential antifungal lead compounds. The structure-activity relationships (SAR) were discussed in terms of the effects of the substituents on both the benzene and the sugar ring.

1. Introduction

Carbohydrates play an important role in the field of pesticide investigation, and many natural carbohydrate products used as pesticides have shown great vitality [1]. Carbohydrate compounds are easy to degrade, have good environmental compatibility [2], and are less resistant to resistance [3]. The new fungicides, which were developed based on carbohydrate compounds, have advantages of safety, high efficiency, low residue and not easy to generate insecticide resistance [4,5], not only ensuring the high yield of vegetables and other agricultural products [6], but also solve the problem of pesticide residues.

Triazole pesticides are the most widely used variety of fungicides in agricultural production, which are mainly divided into fungicides, herbicides, pesticides and plant growth regulators [7]. At this stage, there are more than 30 varieties which have been produced and widely used, such as triazole alcohol [8], triazolone, propiconazole [9], hexaconazole [10] and fluorosilazole [11]. Triazole compounds have been extensively studied in the field of medicine and pesticides, and exhibit a variety of biological activities. In addition to a strong internal fungicidal activity, triazole compounds also have a regulatory role in the growth of plant [12], herbicidal [13], insecticidal [14] and antifungal [15,16]. Because of these multiple effect of the triazole structure, the research of these compounds have been in the ascendant so far. In order to obtain more efficient derivatives, the chemical structure modification of these compounds as well as the research as medicine and veterinary drugs have been frontier issues both at home and abroad for a long time.

Biorational design based on specific target is one of the important means of international new pesticide creation. In the previous research in our laboratory, carbohydrate derivatives of five-membered ring thiadiazole derivatives (I, Figure 1) were synthesized and their fungicidal activities were studied as well [1]. The results of bioactivity determination showed that some compounds exhibited good fungicidal activities against Sclerotinia sclerotiorum (Lib.) de Bary and Pyricularia oryzae Cav. and consistent with their glucosamine-6-phosphate synthase (GlmS [17,18]; EC 2.6.1.16) inhibitory activities.

Inspired by these promising results, based on the structural characteristics of the substrate fructose-6-phosphate and the current research basis [1,19,20,21], we introduced the triazole group which possessed various important bioactivities instead of thiadiazole in this article, six series of novel furan glucosyl triazole compounds were designed and synthesized for the first time, their fungicidal activities against P. CapasiciLeonian, Sclerotinia sclerotiorum (Lib.) de Bary, Botrytis cinerea Pers, Pyricularia oryzae Cav., Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. and enzyme inhibitory activities against Candida albicans GlmS were evaluated. We would like to report their synthesis (Scheme 1) and bioactivities in much greater details, and also their structure-activity relationship studies. We report herein the preliminary results of the study.

2. Results and Discussion

2.1. Synthesis of the Title Compounds

As shown in Scheme 1, we envisioned that the target compounds triazole derivatives 1, 2, 3, 4, 5 and 6 could be synthesized from the intermediates 7 [22] and 8 [23] which could be prepared using 1,2,5,6-di-isopropylidene-d-glucose as the starting material for five steps according to the known methods [22,23]. Then cyclization of 7 and 8 with alkyne provided the desired triazole derivatives 1 and 2 under the conditions of copper sulfate and sodium ascorbate in high yields, respectively. Then the target compounds 3 or 4 were prepared by treating compounds 1 or 2 with 90% trifluoroacetic acid. Compounds 5 or 6 were obtained by acetylation of compound 3 or 4.

All the derivatives were synthesized according to the procedures described in Scheme 1 in good yields of 60–98%. The structures of all the synthesized compounds were confirmed from its ¹H-NMR, ¹³C-NMR spectra and HRMS. The ¹H-NMR experiments of compounds 1/2/5/6 were conducted in CDCl₃ as the solvent. Nevertheless, because of the poor solubility of compounds 3/4, so we had to switch the solvent to methanol-d₄ or DMSO-d₆. The physical data of the target compounds were given in

Table 1. Physical Data of Compounds 1, 2, 3, 4, 5 and 6.

Compd.	R1	R2	Formula	Status	m.p./°C	Yield (%)
1-a	Me	C6H5-	C17H21O4N3	White foamy solid	159.9–160.4	79.4
1-b	Me	3-CH3-C6H4-	C18H23O4N3	Yellow foamy solid	108.0–109.7	79.6
1-c	Me	4-CH3O-C6H4-	C18H23O5N3	White foamy solid	156.6–157.5	69.3
1-d	Me	4-F-C6H4-	C17H20O4N3F	White foamy solid	121.4–122.3	83.0
1-e	Me	4-NO2-C6H4-	C17H20O6N4	White foamy solid	126.5–126.8	77.1
1-f	Me	4-Cl-C6H4-	C17H20O4N3Cl	White foamy solid	135.9–136.7	79.3
1-g	Me	CH3-CH(OH)-	C13H21O5N3	Yellow foamy solid	90.2–90.9	92.3
2-a [24]	Bn	C6H5-	C23H25O4N3	White foamy solid	133.2–134.1	66.0
2-b	Bn	3-CH3-C6H4-	C24H27O4N3	White foamy solid	108.8–110.2	79.4
2-c	Bn	4-CH3O-C6H4-	C24H27O5N3	White foamy solid	134.6–135.7	73.6
2-d	Bn	4-F-C6H4-	C23H24O4N3F	White foamy solid	164.3–164.7	90.4
2-e	Bn	4-NO2-C6H4-	C23H24O6N4	Yellow foamy solid	182.6–183.6	90.3
2-f	Bn	4-Cl-C6H4-	C23H24O4N3Cl	White foamy solid	136.2–136.5	93.7
2-g	Bn	CH3-CH(OH)-	C19H25O5N3	White foamy solid	90.6–90.9	87.6
3-a	Me	C6H5-	C14H17O4N3	White foamy solid	101.1–102.1	78.5
3-b	Me	3-CH3-C6H4-	C15H19O4N3	Oily	——	77.4
3-c	Me	4-CH3O-C6H4-	C15H29O5N3	White foamy solid	130.3–130.8	79.4
3-d	Me	4-F-C6H4-	C14H16O4N3F	White foamy solid	136.5–137.1	64.9
3-e	Me	4-NO2-C6H4-	C14H16O6N4	White foamy solid	149.2–150.1	74.3
3-f	Me	4-Cl-C6H4-	C14H16O4N3Cl	White foamy solid	109.4–110.2	80.7
3-g	Me	CH3-CH(OH)-	C10H16O5N3	Oily	——	60.2
4-a	Bn	C6H5-	C20H21O4N3	White foamy solid	98.7–99.6	80.3
4-b	Bn	3-CH3-C6H4-	C23H21O4N3	White foamy solid	90.2–90.6	74.2
4-c	Bn	4-CH3O-C6H4-	C21H23O5N3	Yellow foamy solid	121.6–123.0	76.8
4-d	Bn	4-F-C6H4-	C20H20O4N3F	White foamy solid	132.7–134.2	80.5
4-e	Bn	4-NO2-C6H4-	C20H20O6N4	White foamy solid	156.2–156.9	81.6
4-f	Bn	4-Cl-C6H4-	C20H20O4N3Cl	Yellow foamy solid	103.7–104.4	73.4
4-g	Bn	CH3-CH(OH)-	C16H21O5N3	White foamy solid	105.7–106.1	87.6
5-a	Me	C6H5-	C18H21O6N3	White foamy solid	140.2–141.1	88.9
5-b	Me	3-CH3-C6H4-	C19H23O6N3	White foamy solid	116.7–118.1	87.4
5-c	Me	4-CH3O-C6H4-	C18H20O7N3	White foamy solid	156.7–157.9	89.4
5-d	Me	4-F-C6H4-	C18H20O6N3F	White foamy solid	141.6–143.6	85.4
5-e	Me	4-NO2-C6H4-	C18H20O8N4	Oily	——	80.3
5-f	Me	4-Cl-C6H4-	C18H20O6N3Cl	White foamy solid	131.3–133.0	90.7
6-a	Bn	C6H5-	C24H25O6N3	White foamy solid	148.0–149.3	87.2
6-b	Bn	3-CH3-C6H4-	C25H27O6N3	White foamy solid	110.7–112.5	82.4
6-c	Bn	4-CH3O-C6H4-	C25H27O7N3	Yellow foamy solid	140.6–141.9	86.7
6-d	Bn	4-F-C6H4-	C24H24O6N3F	White foamy solid	123.8–124.9	85.3
6-e	Bn	4-NO2-C6H4-	C24H24O8N4	Oily	——	86.1
6-f	Bn	4-Cl-C6H4-	C24H24O6N3Cl	White foamy solid	140.6–141.4	88.7

.

2.2. Fungicidal Activity of Compounds 1, 2, 3, 4, 5, 6 against Five Fungus Species

Fungicidal activities of the target compounds 1, 2, 3, 4, 5, 6 against five fungal species were evaluated as previously reported [25] and compared with the commercial fungicide chlorothalonil. The inhibition rates were given in

Table 2. Inhibition rate of target compounds against five fungus species (% control at 50 µg/mL).

Compd.	Inhibition Ratio (%)
	P. CapasiciLeonian	S. sclerotiorum	B. cinerea	Pyricularia oryzae Cav.	Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans.
1-a	60.7	70.2	45.2	72.6	70.1
1-b	61.3	69.4	50.2	55.7	50.4
1-c	60.7	71.5	49.1	67.2	65.1
1-d	80.1	87.6	62.9	81.7	85.6
1-e	82.5	83.9	56.2	51.7	65.8
1-f	81.2	85.1	71.0	82.4	89.0
1-g	40.2	49.2	48.7	43.6	52.7
2-a [24]	48.2	66.6	69.6	73.1	68.1
2-b	65.3	69.0	53.1	59.6	46.8
2-c	59.8	62.8	45.5	60.4	68.5
2-d	76.6	88.1	65.9	57.2	67.3
2-e	84.9	82.5	60.3	52.2	64.1
2-f	86.5	85.3	67.9	60.2	67.9
2-g	50.1	43.9	41.3	51.2	46.7
3-a	40.1	30.3	33.3	61.2	58.7
3-b	35.6	28.4	15.3	35.4	34.1
3-c	38.9	31.5	10.4	30.1	29.3
3-d	50.2	38.4	19.1	47.8	40.2
3-e	44.7	39.6	17.1	23.1	25.6
3-f	46.8	25.3	20.5	50.7	57.6
3-g	23.1	13.7	11.5	21.5	23.4
4-a	21.2	26.4	19.5	37.8	35.4
4-b	29.6	29.9	10.9	27.8	27.1
4-c	30.3	30.5	11.2	32.3	33.1
4-d	35.4	34.7	20.3	35.6	37.8
4-e	39.1	32.1	21.1	30.0	31.9
4-f	38.7	31.7	22.2	40.2	43.1
4-g	24.5	13.5	12.1	21.3	20.9
5-a	42.3	57.6	36.1	62.7	61.3
5-b	37.6	48.5	23.7	42.3	39.2
5-c	47.2	43.1	19.2	40.8	30.0
5-d	65.2	67.6	23.2	69.2	70.9
5-e	67.7	64.9	22.1	56.9	69.5
5-f	68.2	56.1	27.6	60.5	71.5
6-a	23.1	46.7	23.5	32.0	35.9
6-b	30.0	39.8	17.1	42.3	40.8
6-c	31.2	42.8	18.6	28.7	37.6
6-d	57.1	64.7	26.7	50.2	58.6
6-e	50.3	56.3	27.4	48.9	59.3
6-f	51.6	41.2	29.1	40.8	57.8
Chlorothalonil	94.2	95.5	98.0	89.2	94.2

. The determination results showed that, most of the tested compounds displayed a certain degree of fungicidal activity against the five species at the concentration of 50 µg/mL.

In general, the following structure-activity relationships (SAR) in compounds 1, 2, 3, 4, 5 and 6 were observed: (1) As a whole, series 1 and 2 exhibited good fungicidal activities against P. CapasiciLeonian, Sclerotinia sclerotiorum (Lib.) de Bary, Pyricularia oryzae Cav. and Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. than the other series. (2) For the series 1 and 2, the fungicidal activities were increased by improving the electron-withdrawing ability of substituents on the benzene ring such as compounds 1-d (R² = 4-F-C₆H₄-), 1-e (R² = 4-NO₂-C₆H₄-), 1-f (R² = 4-Cl-C₆H₄-), 2-d (R² = 4-F-C₆H₄-), 2-e (R² = 4-NO₂-C₆H₄-) and 2-f (R² = 4-Cl-C₆H₄-); When the substituent group (R²) were substituted phenyl, the fungicidal activities of series compounds were superior to that with substituent alkyl. (3) Compared series 1 and 2, on an overall level the former (R¹ = Me) displayed a better fungicidal activities than the latter (R¹ = Bn). (4) Series 3 and 4 were obtained by deisopropylidenation of the compounds 1 and 2, they had the better water-solubility, but the fungicidal activities of compounds 3 and 4 against five species were decreased obviously. (5) In order to improve the fat solubility, the compounds 5 and 6 were synthesized. The fungicidal activities of compounds 5 and 6 were better than compounds 3 and 4, but lower than compounds 1 and 2.

2.3. Bioassay of Enzyme Inhibitory Activities

Inhibitory activities of all the synthesized compounds towards Candida albicans GlcN-6-P synthase were evaluated using the optimized Elson-Morgan method as previously reported [25]. The absorption value of the solution was measured at 585 nm, and then the concentration was counted by the specification curve which was determined thanks to the relation between the absorption value and the concentration of glucosamine-6-phosphate. The inhibition rates were given in

Table 3. Enzyme inhibition Rate of Compounds 1, 2, 3, 4, 5 and 6 at 0.35 mm.

Compd.	Inhibition Rate (%)	Compd.	Inhibition Rate (%)	Compd.	Inhibition Rate (%)	Compd.	Inhibition Rate (%)
1-a	15.2	2-d	15.5	3-g	31.1	5-c	29.7
1-b	16.1	2-e	18.3	4-a	26.1	5-d	27.9
1-c	11.6	2-f	12.8	4-b	30.5	5-e	24.0
1-d	17.5	2-g	17.8	4-c	19.4	5-f	30.3
1-e	16.0	3-a	35.8	4-d	27.9	6-a	11.2
1-f	26.3	3-b	27.4	4-e	21.4	6-b	21.1
1-g	10.3	3-c	28.1	4-f	28.7	6-c	19.4
2-a	11.1	3-d	33.6	4-g	29.6	6-d	23.5
2-b	14.9	3-e	37.9	5-a	25.7	6-e	25.3
2-c	12.4	3-f	44.1	5-b	23.2	6-f	20.1

at 0.35 mm.

As was shown, most of the tested compounds exhibited some enzyme inhibitory activities against glucosamine-6-phosphate synthase at 0.35 mm. On the whole, Although Series 1 and 2 displayed a better fungicidal activities against five species, they exhibited poor enzyme inhibitory activities. Series 3 and 4 without the OH-protection at both 1- and 2-position exhibited better enzyme inhibitory activities than the other series. By and large, the enzyme inhibitory activities of Series 5 and 6 with the OH-acetylation at 1 and 2-position were better than Series 1 and 2 but lower than Series 3 and 4. Compounds 3-a, 3-d, 3-e and 3-f were more active against glucosamine-6-phosphate synthase than the other compounds.

3. Experimental Section

3.1. General Methods

All starting materials and reagents purchased from Sigma-Aldrich (Beijing, China) and Sinopharm Chemical Reagent Beijing Co., Ltd. (Beijing, China). Solvents were purified in the usual way. All reactions were carried out under a nitrogen atmosphere if necessary. All reactions were monitored by thin-layer chromatography (TLC) (the Silica gel thin plate purchased from Yantai Dexin Biological Technology Co., Ltd., Yantai, China) analysis and TLC was performed on silica gel HF with detection by charring with 30% (v/v) H₂SO₄ in CH₃OH or by UV detection (254 nm). Column chromatography was conducted by elution of a column (8 × 100, 16 × 240, 18 × 300, 35 × 400 mm) of silica gel (200–300 mesh) with EtOAc–PE (b. p. 60–90 °C) as the eluent. Optical rotations were recorded using a Perkin-Elmer 241 polarimeter (Perkin-Elmer, Waltham, MA, USA). ¹H-NMR (400 MHz) and ¹³C-NMR (100 MHz) spectra was recorded in CDCl₃, Meth-d₄ or DMSO-d₆ with a Bruker DPX400 spectrometer (Brook (Beijing) science and Technology Co., Ltd., Beijing, China), using Tetramethyl silane (TMS) as internal standard; Mass spectra were obtained with Agilent 1100 series LC/MSD mass spectrometer (Agilent Technologies Inc., Beijing, China). High-resolution mass spectra (HRMS) were performed by the Peking University. Melting points were measured on a Yanagimoto melting-point apparatus (Yanagimoto MFG CO, Kyoto, Japan) and are uncorrected. Solutions were concentrated at a temperature <60 °C under diminished pressure.

3.2. Chemical Synthesis

General procedure for the synthesis of title compounds 1/2. To a soln of compound 7 [22] or 8 [23] (1.5 g) in 1:1:1 CH₂Cl₂–CH₃OH–H₂O (30 mL) was added alkyne derivaticves (0.35 mL), CuSO₄·5H₂O (0.45 g) and sodium ascorbate (0.315 g). The mixture was stirred at 40 °C for 10 h, and TLC (6:1 petroleum ether–EtOAc) indicated that the reaction was complete. The aq. soln. was extracted with CH₂Cl₂ (3 × 50 mL), washed with saturated aq. sodium bicarbonate, dried (Na₂SO₄) and concentrated. Purification by silica gel chromatography with 7:1 petroleum ether–EtOAc as the eluent afforded 1 or 2.

General procedure for the synthesis of title compounds 3/4. Compound 1 or 2 (0.8 g) was dissolved in 90% aq trifluoroacetic acid (20 mL) and then stirred at 40 °C for 4 h, and TLC (1:1 petroleum ether–EtOAc) indicated that the reaction was complete. The trifluoroacetic acid was evaporated under reduced pressure, then the residue was diluted with CH₂Cl₂ (50 mL), washed with saturated aq. sodium bicarbonate, and dried over Na₂SO₄. The soln was concentrated, and the residue was subjected to column chromatography (2:1 petroleum ether–EtOAc) to give the desired product 3/4.

General procedure for the synthesis of title compounds 5/6. To a stirred of compound 3 or 4 (0.4 g) in pyridine (5 mL) was added acetic anhydride (3 mL). The mixture was stirred for a further 3 h, at the end of which time TLC (eluent: 4:1 petroleum ether–EtOAc) indicated that the reaction was complete. The solvents were evaporated under reduced pressure to give a crude product, which was purified on silica gel column chromatography with 5:1 petroleum ether–EtOAc as the eluent to give the compounds 5/6.

Furan glucosyl-1,2,3-triazole (1-a). Yield: 79.4%. White solid, m.p. 159.9–160.4 °C. ¹H-NMR (CDCl₃): δ 7.89–7.31 (m, 6H, ArH, CCHN), 5.95 (s, 1H, H-1), 4.77–3.76 (m, 5H, H-2, H-3, H-4, H-5, H-6), 3.44 (s, 3H, CH₃O), 1.43, 1.30 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 147.44, 130.53, 128.56, 127.81, 125.48, 120.69, 111.74, 105.01, 83.76, 81.16, 78.65, 57.53, 48.82, 26.52, 25.98. ESI-MS m/z calcd. for C₁₇H₂₂O₄N₃ [M + H]⁺ 332.1. Found: 332.1. HRMS for C₁₇H₂₂O₄N₃ [M + H]⁺ 332.1610. Found: 332.1602.

Furan glucosyl-1,2,3-triazole (1-b). Yield: 79.6%. Yellow solid, m.p. 108.0–112.7 °C. ¹H-NMR (CDCl₃): δ 7.88–7.12 (m, 5H, ArH, CCHN), 5.95 (s, 1H, H-1), 4.76–3.75 (m, 5H, H-2, H-3, H-4, H-5, H-6), 3.43 (s, 3H, CH₃O), 2.38 (s, 3H, Ar-Me), 1.43, 1.30 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 138.34, 130.51, 128.77, 128.61, 126.33, 122.78, 120.71, 111.98, 105.17, 83.97, 81.32, 78.82, 57.73, 48.98, 26.68, 26.14, 21.32. ESI-MS m/z calcd. for C₁₈H₂₄O₄N₃ [M + H]⁺ 347.1. Found: 347.1. HRMS for C₁₈H₂₄O₄N₃ [M + H]⁺: 347.1719. Found: 347.1718.

Furan glucosyl-1,2,3-triazole (1-c). Yield: 69.3%. White solid, m.p. 156.6–157.5 °C. ¹H-NMR (CDCl₃): δ 7.82–6.93 (m, 5H, ArH, CCHN), 5.96 (d, 1H, J = 4.0 Hz, H-1), 4.77–4.50 (m, 4H), 3.83–3.76 (m, 4H), 3.44 (s, 3H, CH₃O) 1.43, 1.32 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 159.47, 147.49, 126.90, 123.35, 119.92, 114.12, 111.89, 105.12, 83.91, 81.28, 78.79, 57.67, 55.16, 48.88, 26.63, 26.09. ESI-MS m/z calcd. for C₁₈H₂₄O₅N₃ [M + H]⁺ 362.1. Found: 362.1. HRMS for C₁₈H₂₄O₅N₃ [M + H]⁺ 362.1716. Found: 362.1710.

Furan glucosyl-1,2,3-triazole (1-d). Yield: 83.0%. White solid, m.p. 121.4–122.3 °C. ¹H-NMR (CDCl₃): δ 7.88–7.08 (m, 5H, ArH, CCHN), 5.97 (s, 1H, H-1), 4.78–3.79 (m, 5H, H-2, H-3, H-4, H-5, H-6), 3.45 (s, 3H, CH₃O), 1.43, 1.31 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 163.77, 161.31, 146.83, 127.45, 127.37, 127.07, 126.97, 126.94, 120.57, 115.77, 115.55, 112.00, 105.19, 84.03, 81.33, 78.82, 77.48, 57.73, 49.12, 26.27, 26.12. ESI-MS m/z calcd. for C₁₇H₂₁O₄N₃F [M + H]⁺ 350.1. Found: 350.1. HRMS for C₁₇H₂₁O₄N₃F [M + H]⁺ 350.1516. Found: 350.1515.

Furan glucosyl-1,2,3-triazole (1-e). Yield: 77.1%. White solid, m.p. 126.5–126.8 °C. ¹H-NMR (CDCl₃): δ 8.28–8.01 (m, 5H, ArH, CCHN), 5.99 (s, 1H, H-1), 4.84–3.85 (m, 5H, H-2, H-3, H-4, H-5, H-6), 3.49 (s, 3H, CH₃O), 1.44, 1.33 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃) δ: 147.25, 145.61, 137.04, 126.15, 124.22, 122.49, 112.13, 105.26, 84.16, 81.38, 78.77, 57.85, 49.59, 26.71, 26.15. ESI-MS m/z calcd. for C₁₇H₂₁O₆N₄ [M + H]⁺ 377.1. Found: 377.1. HRMS for C₁₇H₂₁O₆N₄ [M + H]⁺ 377.1461. Found: 377.1461.

Furan glucosyl-1,2,3-triazole (1-f). Yield: 79.3%. White solid, m.p. 135.9–136.7 °C. ¹H-NMR (CDCl₃): δ 7.90–7.37 (m, 5H, ArH, CCHN), 5.97 (s, 1H, H-1), 4.78–3.79 (m, 5H, H-2, H-3, H-4, H-5, H-6) 3.46 (s, 3H, CH₃O) 1.43, 1.31 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 146.74, 133.75, 129.27, 128.98, 127.00, 120.93, 112.10, 105.25, 84.11, 81.38, 78.85, 57.83, 49.27, 26.74, 26.20. ESI-MS m/z calcd. for C₁₇H₂₁O₄N₃Cl [M + H]⁺ 366.1. Found: 366.1. HRMS for C₁₇H₂₁O₄N₃Cl [M + H]⁺ 366.1221. Found: 366.1219.

Furan glucosyl-1,2,3-triazole (1-g). Yield: 92.3%. Yellow solid, m.p. 90.2–90.9 °C. ¹H-NMR (CDCl₃): δ 7.61 (d, J = 4.0 Hz, 1H, CCHN), 5.94 (s, 1H, H-1), 5.09–5.04 (m, 1H, CH₃CHOH), 4.68–4.47 (m, 4H), 3.75 (s, 1H), 3.44 (s, 3H, CH₃O), 1.58 (s, 3H, OH-C-CH₃)1.43,1.30 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 162.75, 152.52, 152.46, 121.43, 112.08, 105.21, 84.00, 81.36, 78.80, 62.83, 62.77, 57.79, 48.99, 29.67, 26.73, 26.19, 23.09, 23.00, 20.96. ESI-MS m/z calcd. for C₁₃H₂₃O₅N₃ [M + H]⁺ 300.1. Found: 300.1. HRMS for C₁₃H₂₃O₅N₃ [M + H]⁺ 300.1559. Found: 300.1555.

Furan glucosyl-1,2,3-triazole (2-a) [24]. Yield: 66.0%. White solid, m.p. 133.2–134.1 °C. ¹H-NMR (CDCl₃): δ 7.79–7.25(m, 11H, ArH, CCHN), 5.96 (s, 1H, H-1), 4.69–4.42 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 3.97 (s, 1H, H-6), 1.40, 1.27 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 147.53, 136.84, 128.60, 128.52, 128.13, 127.86, 127.79, 125.57, 120.73, 111.92, 111.90, 81.86, 81.61, 78.76, 77.48, 76.84, 76.81, 71.87, 49.09, 26.62, 26.08. ESI-MS m/z calcd. for C₂₃H₂₆O₄N₃ [M + H]⁺ 408.1 Found: 408.1. HRMS for C₂₃H₂₆O₄N₃ [M + H]⁺ 408.1923. Found: 408.1922.

Furan glucosyl-1,2,3-triazole (2-b). Yield: 79.4%. White solid, m.p. 108.8–110.2 °C. ¹H-NMR (CDCl₃): δ 7.77–7.09 (m, 11H, ArH, CCHN), 5.98 (s, 1H, H-1), 4.72–4.44 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 3.98 (s, 1H, H-6), 2.36 (s, 3H, CH₃Ar), 1.41,1.29 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 147.72, 138.24, 136.92, 130.51, 128.69, 128.57, 128.17, 127.83, 126.30, 122.77, 120.68, 111.98, 105.18, 81.96, 81.74, 78.84, 71.96, 49.12, 26.67, 26.14, 21.27. ESI-MS m/z calcd. for C₂₄H₂₈O₄N₃ [M + H]⁺ 422.2. Found: 422.2. HRMS for C₂₄H₂₈O₄N₃ [M + H]⁺ 422.2080. Found: 422.2078.

Furan glucosyl-1,2,3-triazole (2-c). Yield: 73.6%. White solid, m.p. 134.6–135.1 °C. ¹H-NMR (CDCl₃): δ 7.73–6.92 (m, 11H, ArH, CCHN), 6.00 (s, 1H, H-1), 4.75–4.48 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 4.01–3.81 (m, 4H, CH₃O, H-6), 1.42, 1.30 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 159.58, 147.64, 136.96, 128.71, 128.32, 127.96, 127.04, 123.42, 120.03, 114.21, 112.13, 105.28, 82.03, 81.78, 78.97, 72.07, 55.29, 49.23, 26.77, 26.24. ESI-MS m/z calcd. for C₂₄H₂₈O₅N₃ [M + H]⁺ 438.2. Found: 438.2. HRMS for C₂₄H₂₈O₅N₃ [M + H]⁺ 438.2029. Found: 438.2044.

Furan glucosyl-1,2,3-triazole (2-d). Yield: 90.4%. White solid, m.p. 164.3–164.7 °C. ¹H-NMR (CDCl₃): δ 7.77–7.06 (m, 10H, ArH, CCHN), 6.00 (s, 1H, H-1), 4.75–4.48 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 4.02 (s, 1H, H-6), 1.42, 1.31 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 146.92, 136.95, 128.73, 128.36, 127.98, 127.53, 127.45, 126.99, 120.63, 115.82, 115.61, 112.18, 105.31, 82.07, 81.83, 78.94, 72.09, 49.40, 26.77, 26.24. ESI-MS m/z calcd. for C₂₃H₂₅O₄N₃F [M + H]⁺ 426.1. Found: 426.1. HRMS for C₂₃H₂₅O₄N₃F [M + H]⁺ 426.1829. Found: 426.1830.

Furan glucosyl-1,2,3-triazole (2-e). Yield: 90.2%. White solid, m.p. 182.6–184.6 °C. ¹H-NMR (CDCl₃): δ 8.28–7.33 (m, 11H, ArH, CCHN), 6.03 (s, 1H, H-1), 4.80–4.50 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 4.07 (s, 1H, H-6), 1.43, 1.33 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 147.33, 145.67, 137.02, 136.90, 128.81, 128.46, 128.03, 126.21, 124.27, 122.51, 112.29, 105.37, 82.08, 81.83, 78.84, 72.12, 49.80, 26.79, 26.25. ESI-MS m/z calcd. for C₂₃H₂₄O₆N₄ [M + H] 453.1. Found: 453.1. HRMS for C₂₃H₂₄O₆N₄ [M + H]⁺ 453.1774. Found: 453.1773.

Furan glucosyl-1,2,3-triazole (2-f). Yield: 93.7%. White solid, m.p. 136.2–136.5 °C. ¹H-NMR (CDCl₃): δ 7.79–7.33 (m, 11H, ArH, CCHN), 6.01 (s, 1H, H-1), 4.77–4.48 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 4.03 (s, 1H, H-6), 1.43, 1.31 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 146.80, 136.94, 133.82, 129.28, 129.02, 128.80, 128.44, 128.03, 127.06, 120.98, 112.24, 105.35, 82.08, 81.82, 78.95, 77.16, 76.84, 72.13, 49.51, 26.82, 26.29. ESI-MS m/z calcd. for C₂₃H₂₅O₄N₃Cl [M + H]⁺ 442.1. Found: 442.1. HRMS for C₂₃H₂₅O₄N₃Cl [M + H]⁺ 442.1534. Found: 442.1533.

Furan glucosyl-1,2,3-triazole (2-g). Yield: 87.6%. White solid, m.p. 90.6–90.9 °C. ¹H-NMR (CDCl₃): δ 7.46–7.23 (m, 6H, ArH, CCHN), 5.86 (s, 1H, H-1), 4.93–4.92 (s, 1H), 4.63–4.39 (m, 6H, H-2, H-3, H-4, H-5, CH₂Ar), 3.89 (s, 1H, H-6), 1.45 (d, J = 4.0 Hz, 3H, OH-C-CH₃) 1.31,1.20 (2s, 6H, Me₂C); ¹³C-NMR (CDCl₃): δ 136.84, 128.51, 128.11, 127.79, 121.33, 111.90, 105.06, 81.87, 81.57, 78.73, 71.87, 62.62, 62.57, 48.99, 26.57, 26.05, 23.04, 22.96. ESI-MS m/z calcd. for C₁₉H₂₇O₅N₃ [M + H]⁺ 376.1. Found: 376.1. HRMS for C₁₉H₂₇O₅N₃ [M + H]⁺ 376.1872. Found: 376.1875.

Furan glucosyl-1,2,3-triazole (3-a). Yield: 78.5%. White solid, m.p. 101.1–102.1 °C. ¹H-NMR (Meth-d₄): δ 8.18–7.21 (m, 5H, ArH, CCHN), 5.26–5.08 (m, 1H, H-1, α and β), 4.82–3.71 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.36 (m, 3H, OMe); ¹³C-NMR (Meth-d₄): δ 148.60, 148.54, 131.65, 131.63, 129.92, 129.27, 126.63, 123.26, 123.09, 104.80, 97.85, 87.13, 86.70, 80.54, 79.71, 77.50, 76.00, 58.42, 52.55, 51.73. ESI-MS m/z calcd. for C₁₄H₁₈O₄N₃ [M + H]⁺ 292.1. Found: 292.1. HRMS for C₁₄H₁₈O₄N₃ [M + H]⁺ 292.1297. Found: 292.1293.

Furan glucosyl-1,2,3-triazole (3-b). Yield: 77.4%. Oily. ¹H-NMR (Meth-d₄): δ 8.19–6.98 (m, 5H, ArH, CCHN), 5.27–5.10 (m, 1H, H-1, α and β), 4.60–3.69 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.32 (s, 3H, CH₃O), 2.20 (s, 3H, Ar-CH₃); ¹³C-NMR (Meth-d₄): δ 148.52, 148.45, 139.68, 131.23, 130.00, 129.80, 127.16, 123.74, 123.24, 123.04, 104.73, 97.80, 87.02, 86.61, 80.44, 79.61, 77.43, 75.84, 58.41, 58.31, 52.55, 51.71, 21.44. ESI-MS m/z calcd. for C₁₅H₂₀O₄N₃ [M + H]⁺ 306.1. Found: 306.1. HRMS for C₁₅H₂₀O₄N₃ [M + H]⁺ 306.1454. Found: 306.1456.

Furan glucosyl-1,2,3-triazole (3-c). Yield: 79.4%. White solid, m.p. 130.3–130.8 °C. ¹H-NMR (Meth-d₄): δ 8.06–6.83 (m, 5H, ArH, CCHN), 5.26–5.07 (m, 1H, H-1, α and β), 4.79–3.98 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.78–3.76 (m, 3H, CH₃O-Ar), 3.20 (m, 3H, OMe); ¹³C-NMR (Meth-d4): δ 160.20, 148.54, 148.48, 127.97, 124.22, 124.19, 122.39, 122.22, 115.33, 104.79, 97.84, 87.11, 86.69, 80.55, 79.69, 77.52, 75.98, 58.41, 58.34, 55.77, 52.47, 51.66. ESI-MS m/z calcd. for C₁₅H₃₀O₅N₃ [M + H]⁺ 322.1. Found: 322.1. HRMS for C₁₅H₃₀O₅N₃ [M + H]⁺ 322.1403. Found: 322.1399.

Furan glucosyl-1,2,3-triazole (3-d). Yield: 64.9%. White solid, m.p. 136.5–137.1 °C. ¹H-NMR (Meth-d₄): δ 8.15–7.00 (m, 5H, ArH, CCHN), 5.27–5.08 (m, 1H, H-1, α and β), 4.76–4.50 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.45–3.20 (m, 3H, OMe); ¹³C-NMR (Meth-d4): δ 163.91, 161.47, 146.40, 146.33, 127.29, 127.21, 126.85, 126.81, 126.78, 121.78, 121.62, 115.48, 115.27, 103.49, 96.55, 85.80, 85.39, 79.20, 78.39, 76.20, 74.66, 57.11, 57.03, 51.21, 50.40. ESI-MS m/z calcd. for C₁₄H₁₇O₄N₃F [M + H]⁺ 310.1. Found: 310.1. HRMS for C₁₄H₁₇O₄N₃F [M + H]⁺ 310.1203. Found: 310.1204.

Furan glucosyl-1,2,3-triazole (3-e). Yield: 74.3%. White solid, m.p. 149.2–150.1 °C. ¹H-NMR (DMSO): δ 8.81–8.14 (m, 5H, ArH, CCHN), 6.19–6.11 (m, 1H, H-1, α and β), 5.00–4.56 (m, 4H), 4.06–3.99 (m, 1H), 3.44–3.37 (m, 3H, OMe); ¹³C-NMR (DMSO): δ 146.69, 146.59, 144.42, 144.20, 137.05, 137.05, 125.98, 125.86, 124.35, 103.29, 96.29, 85.92, 85.07, 78.89, 77.73, 75.39, 74.31, 57.50, 57.44, 51.06, 50.39. ESI-MS m/z calcd. for C₁₄H₁₇O₆N₄ [M + H]⁺ 337.1. Found: 337.1. HRMS for C₁₄H₁₇O₆N₄ [M + H]⁺ 337.1148. Found: 337.1146.

Furan glucosyl-1,2,3-triazole (3-f). Yield: 80.7%. White solid, m.p. 109.4–110.2 °C. ¹H-NMR (Meth-d₄): δ 8.19–7.25 (m, 5H, ArH, CCHN), 5.29–5.10 (m, 1H, H-1, α and β), 5.07–3.72 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.46–3.21 (m, 3H, OMe); ¹³C-NMR (Meth-d₄): δ 133.62, 129.00, 128.98, 128.74, 126.75, 122.20, 122.01, 103.46, 96.56, 85.76, 85.37, 79.21, 78.32, 76.22, 74.59, 57.18, 57.08, 51.32, 50.48. ESI-MS m/z calcd. for C₁₄H₁₇O₄N₃Cl [M + H]⁺ 326.0. Found: 326.0. HRMS for C₁₄H₁₇O₄N₃Cl [M + H]⁺ 326.0908. Found: 326.0906.

Furan glucosyl-1,2,3-triazole (3-g). Yield: 79.1%. Oily. ¹H-NMR (Meth-d₄): δ 7.86–7.83 (m, 1H, CCHN), 5.25–5.05 (m, 1H, H-1, α and β),4.97–4.46 (m, 4H), 4.05–3.69 (m, 2H), 3.36–3.33 (m, 3H, OMe), 1.44–1.42 (m, 3H, CH-CH₃); ¹³C-NMR (Meth-d₄): δ 153.54, 153.49, 123.81, 123.59, 104.76, 97.86, 87.01, 86.63, 80.50, 80.39, 78.80, 79.55, 77.47, 75.84, 63.41, 58.39, 58.31, 58.11, 52.68, 51.82, 23.63. ESI-MS m/z calcd. for C₁₀H₁₈O₅N₃ [M + H]⁺ 260.1. Found: 260.1. HRMS for C₁₀H₁₈O₅N₃ [M + H]⁺ 260.1403. Found: 260.1247.

Furan glucosyl-1,2,3-triazole (4-a). Yield: 80.3%. White solid, m.p. 98.7–99.2 °C. ¹H-NMR (Meth-d₄): δ 8.07–7.14 (m, 11H, ArH, CCHN), 5.29–5.10 (m, 1H, H-1, α and β), 4.77–3.92 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β); ¹³C-NMR (Meth-d₄): δ 148.52, 148.46, 139.16, 139.00, 131.65, 131.61, 129.89, 129.47, 129.46, 129.23, 129.10, 129.01, 128.91, 128.88, 126.61, 123.28, 123.11, 104.79, 97.85, 84.96, 84.56, 80.37, 77.46, 76.44, 73.24, 73.15, 52.65, 51.84. ESI-MS m/z calcd. for C₂₀H₂₂O₄N₃ [M + H]⁺ 368.1. Found: 368.1. HRMS for C₂₀H₂₂O₄N₃ [M + H]⁺ 368.1610. Found: 368.1608.

Furan glucosyl-1,2,3-triazole (4-b). Yield: 74.2%. White solid, m.p. 90.2–90.6 °C. ¹H-NMR (Meth-d₄): δ 8.03–6.98 (m, 10H, ArH, CCHN), 5.28–5.10 (m, 1H, H-1, α and β), 4.75–3.91 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β), 2.22 (s, 3H, Ar-Me); ¹³C-NMR (Meth-d₄): δ 147.33, 147.27, 138.38, 137.87, 137.71, 130.20, 128.63, 128.50, 128.17, 128.16, 127.79, 127.70, 127.60, 127.58, 125.88, 122.46, 121.94, 121.75, 103.49, 96.55, 83.68, 83.28, 79.07, 76.16, 75.14, 71.94, 71.84, 51.32, 50.51, 20.17. ESI-MS m/z calcd. for C₂₃H₂₂O₄N₃ [M + H]⁺ 382.1. Found: 382.1. HRMS for C₂₃H₂₂O₄N₃ [M + H]⁺ 382.1767. Found: 382.1766.

Furan glucosyl-1,2,3-triazole (4-c). Yield: 76.8%. Yellow solid, m.p. 121.6–123.0 °C. ¹H-NMR (Meth-d₄): δ 7.98–6.79 (m, 10H, ArH, CCHN), 5.30–5.11 (m, 1H, H-1, α and β), 4.60–3.92 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β), 3.63(s, 3H, Ar-O-Me); ¹³C-NMR (Meth-d₄): δ 161.23, 139.11, 138.96, 129.45, 129.06, 128.97, 128.89, 128.87, 128.02, 122.42, 115.34, 104.78, 97.88, 84.94, 84.57, 80.31, 77.44, 76.32, 73.22, 73.12, 55.77, 52.76, 51.93. ESI-MS m/z calcd. for C₂₁H₂₄O₅N₃ [M + H]⁺ 398.1. Found: 398.1. HRMS for C₂₁H₂₄O₅N₃ [M + H]⁺ 398.1716. Found: 398.1715.

Furan glucosyl-1,2,3-triazole (4-d). Yield: 80.5%.White solid, m.p. 132.7–134.2 °C. ¹H-NMR (Meth-d₄): δ 8.07–6.98 (m, 10H, ArH, CCHN), 5.30–5.10 (m, 1H, H-1, α and β), 5.02–4.04 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β); ¹³C-NMR (Meth-d₄): δ 164.27, 162.82, 139.13, 138.97, 129.48, 129.47, 129.11, 129.01, 128.64, 123.29, 123.10, 116.82, 116.60, 104.80, 97.90, 84.95, 84.57, 80.35, 77.46, 76.38, 73.27, 73.17, 52.78, 51.96. ESI-MS m/z calcd. for C₂₀H₂₁O₄N₃F [M + H]⁺ 386.1. Found: 386.1. HRMS for C₂₀H₂₁O₄N₃F [M + H]⁺ 386.1516. Found: 386.1515.

Furan glucosyl-1,2,3-triazole (4-e). Yield: 81.6%. White solid, m.p. 156.2–156.9 °C. ¹H-NMR (DMSO): δ 8.80–7.30 (m, 10H, ArH, CCHN), 6.56–6.33 (m, 1H, H-1, α and β), 4.76–4.01 (m, 9H); ¹³C-NMR (DMSO): δ 146.54, 144.21, 138.09, 137.18, 128.26, 127.57, 127.53, 125.82, 124.32, 124.11, 96.30, 96.20, 83.10, 75.34, 74.71, 71.17, 50.53. ESI-MS m/z calcd. for C₂₀H₂₁O₆N₄ [M + H]⁺ 413.1. Found: 413.1. HRMS for C₂₀H₂₁O₆N₄ [M + H]⁺ 413.1461. Found: 413.1460.

Furan glucosyl-1,2,3-triazole (4-f).Yield: 73.4%. White solid, m.p. 103.7–104.4 °C. ¹H-NMR (Meth-d₄): δ 8.08–7.15 (m, 10H, ArH, CCHN), 5.29–5.09 (m, 1H, H-1, α and β), 4.74–3.92 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β); ¹³C-NMR (Meth-d₄): δ 147.39, 147.32, 139.17, 139.01, 134.86, 130.01, 129.48, 129.47, 128.03, 123.49, 123.32, 104.80, 97.86, 84.99, 84.58, 80.39, 80.34, 77.44, 76.45, 73.26, 73.16, 52.71, 51.90. ESI-MS m/z calcd. for C₂₀H₂₁O₄N₃Cl [M + H]⁺ 367.1. Found: 367.1. HRMS for C₂₀H₂₁O₄N₃Cl [M + H]⁺ 402.1221. Found: 402.1220.

Furan glucosyl-1,2,3-triazole (4-g). Yield: 79.7%. White solid, m.p. 105.7–106.1 °C. ¹H-NMR (Meth-d₄): δ 7.75–7.14 (m, 6H, ArH, CCHN), 5.28–5.08 (m, 1H, H-1, α and β), 4.64–4.05 (m, 8H), 1.59–1.56 (m, 3H, CH-CH₃); ¹³C-NMR (Meth-d₄): δ 153.35, 153.26, 139.08, 138.93, 129.41, 128.99, 128.91, 128.89, 123.61, 123.41, 104.65, 97.75, 84.80, 84.78, 84.47, 80.38, 80.20, 77.45, 76.20, 73.13, 73.06, 63.47, 52.52, 51.68, 23.61. ESI-MS m/z calcd. for C₁₆H₂₂O₅N₃ [M + H]⁺ 353.1. Found: 353.1. HRMS for C₁₆H₂₂O₅N₃ [M + H]⁺ 353.1907. Found: 353.1906.

Furan glucosyl-1,2,3-triazole (5-a). Yield: 88.2%. White solid, m.p. 140.2–141 °C. ¹H-NMR (CDCl₃): δ 7.87–7.26 (m, 6H, ArH, CCHN), 6.45–6.14 (m, 1H, H-1, α and β), 5.26–4.42 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β) 3.51–3.45 (m, 3H, OMe, α and β) 2.14–2.03 (m, 6H, Me₂-CO); ¹³C-NMR (CDCl₃): δ 169.61, 169.27, 147.96, 130.62, 128.93, 128.27, 127.70, 125.86, 121.15, 120.89, 99.80, 94.06, 82.77, 82.40, 81.79, 78.62, 78.25, 76.16, 58.45, 58.27, 50.36, 49.88, 21.27, 20.91, 20.82, 20.54. ESI-MS m/z calcd. for C₁₈H₂₂O₆N₃ [M + H]⁺ 376.1. Found: 376.1. HRMS for C₁₈H₂₂O₆N₃ [M + H]⁺ 376.1509. Found: 376.1507.

Furan glucosyl-1,2,3-triazole (5-b). Yield: 79.4%. White solid, m.p. 116.7–118.1 °C. ¹H-NMR (CDCl₃): δ 7.78–7.04 (m, 5H, ArH, CCHN), 6.38–6.08 (m, 1H, H-1, α and β), 5.19–3.79 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β) 3.42–3.37 (m, 3H, OMe, α and β) 2.30 (s, 3H, Ar-CH₃) 2.06–1.95 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 169.52, 169.16, 147.90, 138.46, 130.42, 128.90, 128.71, 126.39, 122.85, 121.04, 120.73, 99.67, 93.93, 82.63, 82.26, 81.72, 78.51, 78.13, 76.09, 58.32, 58.15, 50.22, 49.73, 21.39, 21.15, 20.79, 20.69, 20.43. ESI-MS m/z calcd. for C₁₉H₂₄O₆N₃ [M + H]⁺ 390.1. Found: 390.1. HRMS for C₁₉H₂₄O₆N₃ [M + H]⁺ 390.1665. Found: 390.1668.

Furan glucosyl-1,2,3-triazole (5-c). Yield: 91.9%. White solid, m.p. 156.7–157.9 °C. ¹H-NMR (CDCl₃): δ 7.78–6.93 (m, 5H, ArH, CCHN), 6.45–6.15 (m, 1H, H-1, α and β), 5.26–4.40 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.82 (m, 3H, Ar-OMe), 3.50–3.45 (m, 3H, OMe), 2.14–2.03 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 169.61, 169.26, 159.74, 147.84, 127.16, 123.40, 120.31, 120.04, 114.36, 99.81, 94.10, 82.74, 82.44, 81.85, 78.62, 78.33, 76.16, 58.43, 58.25, 55.41, 50.25, 49.79, 21.26, 20.90, 20.81, 20.54. ESI-MS m/z calcd. for C₁₈H₂₁O₇N₃ [M + H]⁺ 406.1. Found: 406.1. HRMS for C₁₈H₂₁O₇N₃ [M + H]⁺ 406.1614. Found: 406.1612.

Furan glucosyl-1,2,3-triazole (5-d). Yield: 90.7%. White solid, m.p. 141.6–143.6 °C. ¹H-NMR (CDCl₃): δ 7.78–7.00 (m, 5H, ArH, CCHN), 6.38–6.08 (m, 1H, H-1, α and β), 5.20–3.81 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.44–3.38 (m, 3H, OMe), 2.07–1.96 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 169.48, 169.43, 169.12, 163.85, 161.39, 146.92, 127.49, 127.41, 120.83, 120.53, 115.84, 115.62, 99.66, 93.88, 82.65, 82.22, 81.66, 78.49, 78.04, 76.06, 58.30, 58.14, 50.32, 49.82, 21.10, 20.74, 20.65, 20.38. ESI-MS m/z calcd. for C₁₈H₂₀O₆N₃F [M + H]⁺ 394.1. Found: 394.1. HRMS for C₁₈H₂₀O₆N₃F [M + H]⁺ 394.1414. Found: 394.1414.

Furan glucosyl-1,2,3-triazole (5-e). Yield: 84.7%. Oily.¹H-NMR (CDCl₃): δ 8.27–7.26 (m, 5H, ArH, CCHN), 6.45–6.15 (m, 1H, H-1, α and β), 5.28–3.92 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.53–3.47 (m, 3H, OMe, α and β), 2.15–2.03 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 169.61, 169.24, 147.46, 145.81, 136.94, 126.29, 124.38, 122.70, 122.39, 99.82, 93.95, 82.86, 82.31, 81.71, 78.55, 78.00, 76.20, 58.48, 58.33, 50.86, 50.32, 21.26, 20.89, 20.79, 20.53. ESI-MS m/z calcd. for C₁₈H₂₁O₈N₄ [M + H]⁺ 421.1. Found: 421.1. HRMS for C₁₈H₂₁O₈N₄ [M + H]⁺ 421.1359. Found: 421.1357.

Furan glucosyl-1,2,3-triazole (5-f). Yield: 82.9%. White solid, m.p. 131.3–133.0 °C. ¹H-NMR (CDCl₃): δ 7.87–7.27 (m, 5H, ArH, CCHN), 6.45–6.15 (m, 1H, H-1, α and β), 5.27–3.90 (m, 5H, H-2, H-3, H-4, H-5, H-6, α and β), 3.52–3.46 (m, 3H, OMe, α and β), 2.15–2.04 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 169.61, 169.56, 169.25, 146.95, 134.02, 129.21, 129.14, 127.12, 121.21, 120.92, 99.82, 94.05, 82.81, 82.40, 81.81, 78.59, 78.21, 76.18, 58.47, 58.29, 50.53, 50.03, 21.28, 20.92, 20.82, 20.55. ESI-MS m/z calcd. for C₁₈H₂₁O₆N₃Cl [M + H]⁺ 410.1. Found: 410.1. HRMS for C₁₈H₂₁O₆N₃Cl [M + H]⁺ 410.1119. Found: 410.1120.

Furan glucosyl-1,2,3-triazole (F-a). Yield: 90.3%. White solid, m.p. 148.0–149.3 °C. ¹H-NMR (CDCl₃): δ 7.70–7.21 (m, 11H, ArH, CCHN), 6.40–6.10 (m, 1H, H-1, α and β), 5.25–4.00 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β), 2.04–1.93 (m, 6H, Me₂-CO); ¹³C-NMR (CDCl₃): δ 169.50, 169.16, 147.71, 136.93, 136.73, 130.54, 128.77, 128.67, 128.61, 128.33, 128.24, 128.10, 128.01, 127.98, 125.72, 121.16, 120.89, 99.70, 94.03, 81.67, 80.12, 80.05, 78.92, 78.12, 76.48, 72.43, 72.18, 50.35, 49.86, 21.13, 20.78, 20.69, 20.42. ESI-MS m/z calcd. for C₂₄H₂₆O₆N₃ [M + H]⁺ 452.1. Found: 452.1. HRMS for C₂₄H₂₆O₆N₃ [M + H]⁺ 452.1822. Found: 452.1821.

Furan glucosyl-1,2,3-triazole (6-b). Yield: 91.6%. White solid, m.p. 110.7–112.5 °C. ¹H-NMR (CDCl₃): δ 7.67–6.95 (m, 10H, ArH, CCHN), 6.35–6.06 (m, 1H, H-1, α and β), 5.20–3.96 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β) 2.22 (s, 3H, Ar-CH₃), 1.97–1.86 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 169.25, 168.90, 147.43, 138.12, 136.84, 136.65, 130.28, 128.58, 128.44, 128.38, 128.33, 128.00, 127.92, 127.75, 127.70, 126.08, 122.58, 120.98, 120.68, 99.40, 93.72, 81.43, 79.97, 79.79, 78.70, 76.84, 76.30, 72.16, 71.91, 50.09, 49.58, 21.13, 20.84, 20.49, 20.40, 20.14. ESI-MS m/z calcd. for C₂₅H₂₈O₆N₃ [M + H]⁺ 466.1. Found: 466.1. HRMS for C₂₅H₂₈O₆N₃ [M + H]⁺ 466.1978. Found: 466.1980.

Furan glucosyl-1,2,3-triazole (6-c). Yield: 92.5%. Yellow solid, m.p. 140.6–141.9 °C. ¹H-NMR (CDCl₃): δ 7.89–6.85 (m, 10H, ArH, CCHN), 6.49–6.19 (m, 1H, H-1, α and β), 5.24–4.03 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β), 3.83 (s, 3H, Ar-CH₃), 2.11–2.04 (m, 6H, Me₂-CO, α and β); ¹³C-NMR (CDCl₃): δ 170.24, 169.87, 159.71, 159.66, 147.61, 147.55, 137.09, 137.06, 128.78, 128.72, 128.69, 128.31, 128.28, 128.06, 127.11, 123.51, 120.28, 120.12, 114.32, 114.29, 108.00, 100.77, 94.18, 80.80, 80.40, 80.34, 79.89, 78.62, 75.68, 72.51, 72.28, 55.40, 50.33, 49.90, 20.92, 20.81, 20.74, 20.54. ESI-MS m/z calcd. for C₂₅H₂₈O₇N₃ [M + H]⁺ 482.1. Found: 482.1. HRMS for C₂₅H₂₈O₇N₃ [M + H]⁺ 482.1927. Found: 482.1927.

Furan glucosyl-1,2,3-triazole (6-d). Yield: 87.1%. White solid, m.p. 123.8–124.9 °C. ¹H-NMR (CDCl₃): δ 7.68–6.98 (m, 10H, ArH, CCHN), 6.41–6.11 (m, 1H, H-1, α and β), 5.26–4.01 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β), 2.06–1.95 (m, 6H, Me₂-CO); ¹³C-NMR (CDCl₃): δ 169.66, 169.58, 169.49, 169.24, 163.93, 161.47, 146.96, 146.94, 136.94, 136.74, 128.75, 128.70, 128.43, 128.34, 128.08, 128.06, 127.57, 127.48, 120.97, 120.71, 115.91, 115.69, 99.77, 94.08, 81.74, 80.15, 80.08, 78.96, 78.16, 76.53, 72.51, 72.24, 50.51, 50.02, 21.20, 20.85, 20.77, 20.49. ESI-MS m/z calcd. for C₂₄H₂₅O₆N₃F [M + H]⁺ 470.1. Found: 470.1. HRMS for C₂₄H₂₅O₆N₃F [M + H]⁺: 470.1727. Found: 470.1736.

Furan glucosyl-1,2,3-triazole (6-e). Yield: 89.4%. Oily. ¹H-NMR (CDCl₃): δ 8.18–7.26 (m, 10H, ArH, CCHN), 6.42–6.12 (m, 1H, H-1, α and β), 5.28–4.06 (m, 7H, H-2, H-3, H-4, H-5, H-6, Ar-CH₂, α and β) 2.07–1.96 (m, 6H, Me₂-CO); ¹³C-NMR (CDCl₃): δ 169.61, 169.25, 147.36, 145.63, 136.89, 136.86, 136.69, 128.79, 128.73, 128.49, 128.40, 128.09, 128.07, 126.22, 126.20, 124.28, 122.82, 122.53, 99.78, 93.98, 81.61, 80.21, 80.00, 78.94, 77.90, 76.54, 72.57, 72.28, 50.85, 50.34, 21.21, 20.86, 20.77, 20.49. ESI-MS m/z calcd. for C₂₄H₂₅O₈N₄ [M + H]⁺ 497.1. Found: 497.1. HRMS for C₂₄H₂₅O₈N₄ [M + H]⁺: 497.1672. Found: 497.1684.

Furan glucosyl-1,2,3-triazole (6-f). Yield: 92.8%. White solid, m.p. 140.6–141.4 °C. ¹H-NMR (CDCl₃): δ 7.78–7.31 (m, 10H, ArH, CCHN), 6.47–6.18 (m, 1H, H-1, α and β), 5.33–4.09 (m, 7H, H-2, H-3, H-4,H-5,H-6, Ar-CH₂, α and β), 2.11–2.01 (m, 6H, Me₂-CO); ¹³C-NMR (CDCl₃): δ 169.49, 169.14, 149.62, 146.67, 136.91, 136.71, 136.11, 133.79, 129.15, 128.97, 128.70, 128.64, 128.37, 128.28, 128.02, 128.00, 126.98, 123.79, 121.25, 120.97, 99.71, 94.00, 81.65, 80.15, 80.03, 78.92, 78.04, 76.49, 72.47, 72.20, 50.48, 49.99, 21.14, 20.79, 20.70, 20.43. ESI-MS m/z calcd. for C₂₄H₂₅O₆N₃Cl [M + H]⁺ 486.1. Found: 486.1. HRMS for C₂₄H₂₅O₆N₃Cl [M + H]⁺ 486.1432. Found: 486.1437.

3.3. Fungicidal Assays

The fungicidal activity was determined by mycelium growth rate test as previously reported [25]. Each of the test compounds was dissolved in DMSO (10 mL). The culture media, with known concentration of the test compounds, were obtained by mixing the soln of compounds 1–6 in DMSO with potato dextrose agar (PDA), on which fungus cakes were placed. The blank test was made using DMSO. The commercial fungicide chlorothalonil was used as a control in the above bioassay. The culture was carried out at 24 ± 0.5 °C. Three replicates were performed. Inhibition rates of compounds 1–6 against P. CapasiciLeonian, Sclerotinia sclerotiorum (Lib.) de Bary, B. cinerea, Pyricularia oryzae Cav. and Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. at 50 μg/mL were given in Table 2.

3.4. Enzyme Inhibitory Activities Bioassay

Inhibitory activity of all the synthesized compounds towards Candida albicans GlcN-6-P synthase was determined using the optimized Elson-Morgan method as previously reported [25]. Absorbance at λ = 585 nm was measured and GlcN-6-P concentration in the sample was read from the standard curve (Solutions of glucosamine-HCl (0.1–1 mM) were assayed simultaneously, to obtain a standard line from the plot of extinction against concentration of glucosamine). In each experiment, two control samples, one without enzyme and one without substrates, were assayed in the same way. Three replicates were performed. The inhibition rates were given in Table 3 at 0.35 mm.

4. Conclusions

In summary, forty compounds of triazole were synthesized in an efficient and practical way, thirty-nine of them were new compounds, and the bioactivities of all the compounds were evaluated. The bioassays showed that they had the inhibitory activities against glucosamine-6-phosphate synthase, at the same times, most of them also exhibited good fungicidal activity against P. CapasiciLeonian, Sclerotinia sclerotiorum (Lib.) de Bary, Pyricularia oryzae Cav. and Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. Especially the compounds 1-d and 1-f displayed good fungicidal activities against Sclerotinia sclerotiorum (Lib.) de Bary and Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. They were close to the commercial fungicide chlorothalonil. In the same series, the compounds which exhibited good fungicidal activities were consistent with their glucosamine-6-phosphate synthase inhibitory activities, and the benzene ring with electron-withdrawing substituents (such as fluorine, chlorine, nitro) made the activity increased. The compounds with the OH-protection at both 1 and 2-position in sugar ring exhibited better fungicidal activities than those without protection, but had less inhibitory activities against Glms, which may be associated with a better structural similarity between fructose-6-phosphate and the compounds without protection. Further studies are in progress.