Synthesis of 2-deoxy-C-glycosides via Lewis acid-mediated rearrangement of 2,3-anhydro-1-thiopyranosides

Abstract

An approach to the regio- and stereo-selective construction of 2-deoxy-C-glycosides via Lewis acid-mediated rearrangement of 2,3-anhydro-1-thiopyranosides is disclosed. Treatment of 2,3-anhydro-1-thiopyranosides with phenols in the presence of TMSOTf, the migration–O-glycosylation and Fries-like O to C rearrangement took place in succession, providing aryl 2-thio-2-deoxy-C-glycosides with the single thermodynamically favourable configuration (¹C₄ or ⁴C₁) in good to excellent yields. The coupling reaction of 2,3-anhydro-1-thiopyranosides with trimethylsilylated or tributylstanylated nucleophiles in the presence of TMSOTf or Sc(OTf)₃, via the migration–C-glycosylation process, afforded 2-thio-2-deoxy-C-glycosides in a stereospecific manner in moderate to good yields and with the C-1 and C-2 substituents opposite. The 2-thio-functionality was further removed to produce the corresponding 2-deoxy-C-glycosides. This method may provide a convenient route for the preparation of 2-deoxy-C-glycosides.

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Introduction

C-Glycosides are a class of carbohydrate analogues in which the glycosidic oxygen is replaced by a carbon atom. This novel C–C glycosidic bond is unique and it confers remarkable stability to both enzymatic and/or chemical hydrolysis. In addition, C-glycosides exist in natural products and exhibit a diverse range of biological activities.¹ In particular, the 2-deoxy-C-glycoside structure is embodied in a variety of therapeutically important natural products such as pluramycins, galtamycin, and aquayamycin.² Therefore, the synthesis of C-glycosides has been one of the main topics in carbohydrate chemistry. The stereoselective assembly of 2-deoxy-C-glycosyl linkages is more challenging than that of other C-glycosyl linkages due to the non-existence of participating groups at the 2-position. So far, a series of chemical transformations have been reported for the synthesis of 2-deoxy-C-glycosides,³ these transformations mainly include the electrophilic reaction,⁴ cross-coupling reaction,⁵ free radical reaction,⁶ cyclization,⁷ intramolecular O–C rearrangement,⁸ umpolung,⁹ and other miscellaneous reactions. These reactions involve various glycosyl donors such as glycosyl halides,¹⁰ glycosyl acetates,¹¹ and glycals.¹² Although advances have been made, stereospecific C-glycosylation remains a difficult task. Therefore, it would be highly desirable to develop new approaches to synthesize diverse 2-deoxy-C-glycosides.

2,3-Anhydro-1-thioglycosides¹³ are a type of intriguing donor. They can undergo stereoselectivity-controllable glycosylation reactions generating 2-thio-2-deoxyglycosides. These coupling reactions occurred both regio- and stereo-selectively: the arylthio groups migrated to the position 2 and the nucleophile attacked at the anomeric position; the groups at C-1 and C-2 adopt the trans-configuration and the substituents at C-1 and C-3 adopt the cis-configuration. Inspired by these results, we reasoned that C-glycosylation might highly benefit from 2,3-anhydro-1-thioglycosides. Herein we report C-glycosylations of 2,3-anhydro-1-thioglycosides with phenols via O–C rearrangement or with trimethylsilylated (tributylstanylated) nucleophiles.

Results and discussion

Firstly, p-tolyl 2,3-anhydro-4,6-di-O-benzyl-1-thio-β-D-allopyranoside (1) was prepared (Scheme 1). Treatment of thioglycoside 1a^13a,j with CSA in MeOH provided the de-benzylidene product 1b in 54% yield. By using Ag₂O, O-benzylation of 1b proceeded very smoothly and compound 1 was obtained in 91% yield. Next, the reaction of 2,3-anhydro-1-thio-β-glycoside 1 with m-methoxyphenol (3a) was carried out to explore the feasibility of C-glycosylation of 1 (Table 1). As expected, the reaction of 1 and 3a in the presence of BF₃·Et₂O afforded the desired 2-tolylthio-C-glycoside 4a in 9% yield with high β-selectivity (entry 1). Encouraged by this result, a series of other Lewis acids including SnCl₄, TMSOTf, Sc(OTf)₃, and Cu(OTf)₂ were screened in order to find out the optimal conditions (entries 2–5). The results indicated that the reaction displayed the highest efficiency when TMSOTf was used (entry 3, 65% yield), whereas Sc(OTf)₃ and SnCl₄ took the second place in around 50% yield (entries 2 and 4). Notably, the use of Cu(OTf)₂ resulted in no detectable product 4a (entry 5). Therefore, TMSOTf was chosen as the preferred Lewis acid in the following experiments.

Scheme 1 Synthesis of 2,3-anhydro-1-thioglycoside 1. (a) CSA, MeOH, 54%; (b) 1b (1.0 equiv.), BnBr (7.5 equiv.), Ag₂O (8.0 equiv.), KI (8.0 equiv.), 91%.

Table 1 Screening of optimal reaction conditions^a

Entry	Lewis acid	Yield^b (%)	β/α ratio^c
a Conditions: 1 (0.122 mmol), 3a (0.146 mmol) and Lewis acid (0.122 mmol) in CH2Cl2 (3 mL) from −78 °C to rt. b Isolated yield after chromatography. c Ratio determined by ^1H NMR spectra after chromatography.
1	BF3·Et2O	9	1 : 0
2	SnCl4	46	1 : 0
3	TMSOTf	65	1 : 0
4	Sc(OTf)3	55	1 : 0
5	Cu(OTf)2	0	—

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With the above optimized conditions in hand, we next turned our attention to exploration of the scope of phenols for C-glycosylation with 1 in the presence of TMSOTf (Table 2, entries 1–4). The results showed that electron-rich phenols 3b–3e were suitable substrates for this reaction. Reaction of 3,4-dimethoxyphenol (3b) with 1 afforded product 4b with β-configuration in 90% yield (entry 1), and reaction of 3,5-dimethoxyphenol (3c) with 1 furnished product 4c with α-configuration in 65% yield (entry 2). Gratifyingly, reactions of 2-naphthol (3d) and 7-methoxy-2-naphthol (3e) provided products 4d and 4e with α-configuration in 71% and 73% yield, respectively (entries 3 and 4).

Table 2 The O–C rearrangement reactions of 1 or 2 with phenols^a

Entry	Donor	Acceptor	Product	Yield^b [%]	β/α ratio^c
a Conditions: 1 or 2 (0.122 mmol), acceptor (0.146 mmol), TMSOTf (0.122 mmol) and 4 Å MS in CH2Cl2 (3 mL) from −78 °C to rt. b Isolated yield after chromatography. c Ratio determined by ^1H NMR spectra after chromatography.
1	1			90	0 : 1
2	1			65	1 : 0
3	1			71	1 : 0
4	1			73	1 : 0
5	2	3a		81	0 : 1
6	2	3d		79	0 : 1

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To investigate the influence of the anomeric configuration of thioglycosides, ethyl 2,3-anhydro-1-thio-α-glycoside 2 was prepared (Scheme 2). Initially, ethyl 4,6-O-benzylidene-1-thio-α-D-glucopyranoside (2a)^14a was selectively sulfonated at the 2-position to obtain the mono-sulfonate 2b in 85% yield.^14b Then, 2b was treated with sodium methoxide in methanol providing anhydro-glycoside 2c in 81% yield. Next, debenzylidenation of 2c, which was followed by benzylation, gave the desired ethyl 2,3-anhydro-1-thio-α-glycoside 2 smoothly. Subsequently, compound 2 was employed to check the C-glycosylation reaction (Table 2, entries 5 and 6). As shown, the C-glycosylations of 2 with phenols 3a and 3d proceeded with high β-anomeric selectivity in 81% and 79% yield, respectively. It seems that the substituent at C-1 is not always opposite to the thio-group at C-2 when phenols are used as substrates. The aryl group at C-1 always occupies the equatorial position.

Scheme 2 Synthesis of anhydro-thio-α-glycoside 2. (a) 2a (1.0 equiv.), TsCl (2.0 equiv.), Ag₂O (2.0 equiv.), KI (0.4 equiv.), CH₂Cl₂, 12 h; (b) 2b (1.0 equiv.), NaOMe (3.0 equiv.), MeOH; (c) 2c (1.0 equiv.), CSA (0.3 equiv.), MeOH; (d) 2d (1.0 equiv.), BnBr (7.5 equiv.), Ag₂O (8.0 equiv.), KI (1.0 equiv.), DMF.

Given the successful results from phenols as substrates, we next want to test the reaction of 2,3-anhydro-1-thioglycosides with trimethylsilylated (tributylstanylated) nucleophiles, which failed in the previous report.¹⁵ Thus, upon treatment with TMSOTf at −78 °C, the reaction of anhydro-donor 1 with allyltrimethylsilane (5a) proceeded smoothly, providing C-glycoside 6a with α-anomeric selectivity in 50% isolated yield (Table 3, entry 1). When tributylallylstanane (5b) was used as the substrate, coupling product 6a was also obtained with α-stereoselectivity in 64% yield (Table 3, entry 2). However, under the same conditions, when 1-(trimethylsiloxy)cyclopentene (5c) was used for the reaction, only a small amount of C-glycoside 6b was isolated (10% yield) with α-stereochemistry. Fortunately, compound 6b was prepared from 5c and 1 in an improved yield (51% yield) when Sc(OTf)₃ was used as the promoter (Table 3, entry 3). Similarly, when donor 2 was reacted with 5b in the presence of TMSOTf at −78 °C, coupling product 6c was obtained in 41% yield and with β-stereoselectivity (Table 3, entry 5). Again, using Sc(OTf)₃ as the Lewis acid, the C-glycosylations of 2 with 5a and 5c were greatly improved, producing C-glycosides 6c and 6d with β-stereochemistry in 46% and 70% yield, respectively (Table 3, entries 4 and 6). It is apparent that the group at C-1 is opposite to the thio-group at C-2 when using trimethylsilylated or tributylstanylated nucleophiles as substrates.

Table 3 Reactions of 1 or 2 with trimethylsilylated (tributylstanylated) nucleophiles^a

Entry	Donor	Acceptor	Product	Yield^b [%]	β/α ratio^c
a Conditions: donor (0.122 mmol), acceptor (0.146 mmol), TMSOTf (0.122 mmol) and 4 Å MS in CH2Cl2 (3 mL) from −78 °C to rt. b Isolated yield after chromatography. c Ratio determined by ^1H NMR spectra after chromatography. d Sc(OTf)3 as a Lewis acid.
1	1			50	1 : 0
2	1		6a	64	1 : 0
3	1			10 (51^d)	1 : 0
4	2	5a		Trace (46^d)	0 : 1
5	2	5b	6c	41	0 : 1
6	2	5c		Trace (70^d)	0 : 1

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The anomeric configurations of the coupling products were unambiguously identified by their NMR analyses (Table 4).¹⁶ In the NMR spectra of 4a, the coupling constants of hydrogen signals ³J_H1,H2 = 2.8 Hz (axial–equatorial relationship), ³J_H2,H3 = 2.8 Hz, ³J_H3,H4 = 2.8 Hz, and ³J_H4,H5 = 10.0 Hz (axial–axial relationship), suggest that the sugar ring exists in a ⁴C₁ conformation; the nuclear Overhauser effect (NOE) between H-1 and H-5 indicates that the H-1 is in the axial position. Therefore, the anomeric configuration of 4a is β. By the similar analyses, the NMR data of 4b are consistent with a β-anomeric configuration and a ⁴C₁ conformation. For compound 4c, the values of ³J_H1,H2 = 11.0 Hz (axial–axial relationship), ³J_H3,H4 = 2.0 Hz and ³J_H4,H5 = 3.0 Hz (axial–equatorial relationship) suggest the ¹C₄ conformation and α-anomeric configuration. The structure of 4c was further confirmed by the observations of NOEs between H-1 and H-3, H-1 and H-6. In the same way, the structures of compounds 4d, 4e, 6a, and 6b were identified with α-anomeric configuration and in the ¹C₄ conformation. Compounds 4f, 4g, 6c, and 6d with β-anomeric configuration and in ⁴C₁ conformation were analyzed from their ¹H NMR by a large ³J_H1,H2 coupling constant (>10 Hz, axial–axial relationship).¹⁷

Table 4 Characteristic NMR data of C-glycosyl compounds

Compound	NOE	^3 J H,H [Hz]	Conformation	Configuration
4a	H1↔H5	^3 J H1,H2 = 2.8	^4C1	β
		^3 J H2,H3 = 2.8
		^3 J H3,H4 = 2.8
		^3 J H4,H5 = 10.0
		^3 J H1,H2 = 2.5
4b	H1↔H5	^3 J H2,H3 = 3.5	^4C1	β
		^3 J H3,H4 = 2.5
		^3 J H4,H5 = 10.0
4c	H1↔H3	^3 J H1,H2 = 11.0	^1C4	α
	H1↔H6a	^3 J H3,H4 = 2.0
	H1↔H6b	^3 J H4,H5 = 3.0
4d		^3 J H1,H2 = 10.8	^1C4	α
4e	H1↔H3	^3 J H1,H2 = 10.5	^1C4	α
	H1↔H6a	^3 J H3,H4 = 2.5
	H1↔H6b	^3 J H4,H5 = 2.5
4f		^3 J H1,H2 = 11.0	^4C1	β
4g		^3 J H1,H2 = 10.5	^4C1	β
6a	H1↔H3	^3 J H1,H2 = 6.5	^1C4	α
	H1↔H6a	^3 J H2,H3 = 6.5
	H1↔H6b
6b	H1↔H3	^3 J H1,H2 = 9.0	^1C4	α
	H1↔H6a	^3 J H2,H3 = 9.0
	H1↔H6b
6c		^3 J H1,H2 = 10.5	^4C1	β
6d		^3 J H1,H2 = 11.0	^4C1	β

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After having checked the feasibility of C-glycosylations of 2,3-anhydro-1-thiopyranosides with phenols and trimethylsilylated (tributylstanylated) nucleophiles, the desulfurization of 2-tolylthio-C-glycoside 4b was carried out (Scheme 3). After treatment of 4b with tri-n-butyltin hydride and AIBN in toluene at 105 °C, the 2-deoxy-C-glycoside 7 was obtained in 72% isolated yield. The anomeric configuration of 7 is completely consistent with that identified in 4b.

Scheme 3 Desulfurization of compound 4b. (a) AIBN, n-Bu₃SnH, 105 °C, 72%.

Although the details are not yet known, a proposed mechanism for C-glycosylation is shown in Fig. 1. The reaction may proceed through an oxocarbenium ion A or intermediate B.^13a When phenol as a nucleophile attacks the anomeric carbon at low temperature, a phenolic glycoside C would be generated. During raising the reaction temperature to room temperature, C would rearrange to the thermodynamically favourable C-glycoside G or Hvia the Fries-like O to C rearrangement.¹⁸ The exclusive anomeric configuration may be attributed to the only stable conformation (¹C₄ or ⁴C₁), arising from the severe repulsion between the tolylthio group at C-2 and the aryl group at C-1 with other atoms or groups. Different substituents on phenol may result in different conformations. The aryl group at C-1 is always in the equatorial position, but not always opposite to the thio-group at C-2, as in the case of coupling products 4a and 4b. When the nucleophilic attack is performed by a trimethylsilylated (tributylstanylated) nucleophile, it would form a C-glycoside I with the C-1 and C-2 substituents opposite.

Fig. 1 A proposed pathway leading to C-glycosides.

Conclusions

We have described a new method for the synthesis of 2-deoxy-C-glycosides which is both facile and highly stereoselective. By utilizing 2,3-anhydro-1-thiopyranosides and a variety of nucleophiles, this method affords C-glycosides via the Lewis acid-mediated rearrangement. Promoted by TMSOTf, a reaction of 2,3-anhydro-1-thiopyranosides with phenols gives aryl 2-thio-2-deoxy-C-glycosides, resulting from the successive migration–O-glycosylation and Fries-like O to C rearrangement. These reactions provide C-glycosides with a single anomeric configuration in good to excellent yields. The formed configuration depends on the thermodynamically favourable chair conformation (¹C₄ or ⁴C₁) of the C-glycoside, and the aryl group at C-1 always takes the equatorial position. By treatment of 2,3-anhydro-1-thiopyranosides with trimethylsilylated (tributylstanylated) nucleophiles in the presence of TMSOTf or Sc(OTf)₃, the migration–C-glycosylation reaction proceeds, producing 2-thio-2-deoxy-C-glycosides in moderate to good yields and with the C-1 and C-2 substituents opposite. Finally, treatment of the resulting 2-thio-2-deoxy-C-glycosides with tri-n-butyltin hydride and AIBN can afford the corresponding 2-deoxy-C-glycosides. This method may find applications in the preparation of 2-deoxy-C-glycosides with biological importance.

Experimental section

General methods

All chemicals purchased were of reagent grade and used without further purification, unless noted otherwise. Dichloromethane (CH₂Cl₂) was distilled over calcium hydride (CaH₂). Methanol was distilled from magnesium. DMF was stirred with CaH₂ and distilled under reduced pressure. Toluene was distilled over sodium. All reactions were carried out under anhydrous conditions with freshly distilled solvents, unless stated otherwise. Reactions were monitored by analytical thin-layer chromatography on silica gel 60 F₂₅₄ precoated on aluminium plates. Spots were detected under UV light and/or by staining with acidic ceric ammonium molybdate. Column chromatography was performed on silica gel (200–300 mesh). ¹H-NMR spectra were recorded on a JEOL AL-300, Varian INOVA-500 or Advance DRX Bruker-500 spectrometer at 25 °C. Chemical shifts (in ppm) were referenced to tetramethylsilane (δ = 0 ppm) in deuterated chloroform. ¹³C-NMR spectra were obtained using the same NMR spectrometers and were calibrated with CDCl₃ (δ = 77.00 ppm). Mass spectra were recorded using a PE SCLEX QSTAR spectrometer.

General procedures for C-glycosylations

To a mixture of acceptors (0.146 mmol), donor 1 or 2 (0.122 mmol) and 4 Å molecular sieves was added CH₂Cl₂ (3 mL). The mixture was stirred for 10 min at room temperature and then cooled down to −72 °C. Lewis acid (0.122 mmol) was added and the temperature was raised until TLC showed that the donor was consumed. After neutralization by triethylamine, the reaction mixture was concentrated, and the residue was purified by column chromatography on silica gel to afford product.

p-Tolyl 2,3-anhydro-1-thio-β-D-allopyranoside (1b). To an ice-cooled solution of p-tolyl-2,3-anhydro-4,6-O-benzylidene-1-thio-β-D-allopyranoside (1a)^13a,j (500 mg, 1.40 mmol) in methanol (30 mL) was added D-camphorsulfonic acid (102.6 mg, 0.44 mmol). The mixture was stirred at room temperature for 30 min, followed by addition of triethylamine (0.1 mL). The solution was concentrated, and the residue was purified by column chromatography on silica gel (petroleum ether–ethyl acetate, 1 : 1) to provide 1b (269 mg, 54% yield) as a colorless oil, and unreacted 1a was recovered (90.0 mg, 18%); ¹H NMR (500 MHz, CDCl₃) δ 2.24 (brs, 1H), 2.35 (s, 3H), 2.52 (brs, 1H), 3.37 (d, 1H, J = 4.0 Hz), 3.44–3.48 (m, 1H), 3.66 (d, 1H, J = 4.0 Hz), 3.74 (dd, 1H, J = 5.0 Hz, 12.0 Hz), 3.82–3.85 (m, 2H), 5.16 (d, 1H, J = 8.5 Hz), 7.14 (d, 2H, J = 7.5 Hz), 7.43 (d, 1H, J = 8.5 Hz); ¹³C NMR (125 MHz, CDCl₃) δ 21.16, 54.82, 59.16, 62.54, 65.64, 74.58, 79.95, 127.66, 129.84, 133.55, 138.82; HRMS (ESI) Anal. calcd for C₁₃H₁₆O₄S [M + NH₄]⁺: 286.1108, found: 286.1108.

p-Tolyl 2,3-anhydro-4,6-di-O-benzyl-1-thio-β-D-allopyranoside (1). To a solution of 1b (203 mg, 0.76 mmol) in DMF (10 mL) was added Ag₂O (1.4 g, 6.05 mmol), KI (1.0 g, 6.05 mmol) and BnBr (0.67 mL, 5.66 mmol). After stirring for 8 h at room temperature, the reaction mixture was concentrated. The mixture was filtered and the filtrate was concentrated to give a residue that was purified by column chromatography on silica gel (petroleum ether–ethyl acetate, 12 : 1) to yield 1 (308 mg, 91% yield) as a colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 2.30 (s, 3H), 3.28 (d, 1H, J = 4.5 Hz), 3.56 (d, 1H, J = 4.0 Hz), 3.64 (dd, 1H, J = 4.5 Hz, 11.0 Hz), 3.68–3.72 (m, 2H), 3.77 (dd, 1H, J = 1.5 Hz, 9.5 Hz), 4.54–4.63 (m, 3H), 5.13 (s, 1H), 7.03 (d, 2H, J = 8.0 Hz), 7.24–7.35 (m, 10H), 7.44–7.47 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 21.07, 52.39, 58.46, 69.10, 71.55, 71.67, 72.82, 73.22, 80.09, 127.42, 127.57, 127.81, 127.84, 128.21, 128.32, 129.52, 133.37, 137.67, 138.17, 138.32; HRMS (ESI) Anal. calcd for C₂₇H₂₈O₄S [M + NH₄]⁺: 466.2047, found: 466.2049.

Ethyl 2,3-anhydro-4,6-O-benzylidene-1-thio-α-D-mannopyranoside (2c). To a solution of ethyl 4,6-O-benzylidene-1-thio-α-D-glucopyranoside (2a)¹⁴ (2.00 g, 4.29 mmol) in CH₂Cl₂ (50 mL) was added Ag₂O (1.94 g, 8.39 mmol), KI (0.33 g, 1.99 mmol) and toluenesulfonyl chloride (1.60 g, 8.39 mmol). The reaction mixture was stirred for 12 h. Then the mixture was filtered and the filtrate was concentrated to yield the crude product which was purified by column chromatography on silica gel (petroleum ether–ethyl acetate, 5 : 1, containing 1% triethylamine), providing compound 2b (2.55 g, 85% yield) as a white solid.

To a solution of 2b (1.95 g, 4.18 mmol) in MeOH (25 mL) was added NaOMe (30% in MeOH, 3 mL, 15.99 mmol). After stirring for 1 d at room temperature, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate. Then the solution was washed with brine and water. The organic layer was dried, filtered, and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether–ethyl acetate, 15 : 1, containing 1% triethylamine) to yield 2c (0.99 g, 81% yield) as a white solid; ¹H NMR (500 MHz, CDCl₃) δ 1.33 (t, 3H, J = 7.5 Hz), 2.67 (qd, 1H, J = 7.5 Hz, 13.0 Hz), 2.77 (qd, 1H, J = 7.5 Hz, 13.0 Hz), 3.28 (d, 1H, J = 4.0 Hz), 3.50 (d, 1H, J = 3.5 Hz), 3.72 (d, 1H, J = 10.5 Hz), 3.76 (d, 1H, J = 10.0 Hz), 3.93 (td, 1H, J = 4.5 Hz, 10.0 Hz), 4.22 (dd, 1H, J = 4.5 Hz, 10.5 Hz), 5.51 (s, 1H), 5.57 (s, 1H), 7.35–7.41 (m, 3H), 7.49–7.52 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 15.09, 25.20, 51.90, 53.96, 62.05, 69.33, 75.28, 80.15, 102.44, 126.17, 128.36, 129.27, 137.02; HRMS (ESI) Anal. calcd for C₁₅H₁₈O₄S [M + Na]⁺: 317.0818, found: 317.0821.

Ethyl 2,3-anhydro-1-thio-α-D-mannopyranoside (2d). To an ice-cooled solution of 2c (250 mg, 0.85 mmol) in MeOH (20 mL) was added D-camphorsulfonic acid (63.5 mg, 0.27 mmol). The mixture was stirred at room temperature for 30 min, followed by addition of triethylamine (0.1 mL). The solution was concentrated and the residue was purified by column chromatography on silica gel (petroleum ether–ethyl acetate, 1 : 1) to yield 2d (70.1 mg, 40% yield) as a colorless oil and recovered the unreacted 2c (70.0 mg, 28%); ¹H NMR (500 MHz, CDCl₃) δ 1.33 (t, 3H, J = 7.5 Hz), 1.62 (s, 1H), 1.92 (t, 1H, J = 6.0 Hz), 2.55 (d, 1H), 2.63–2.78 (m, 2H), 3.27 (d, 1H, J = 3.5 Hz), 3.33 (d, 1H, J = 3.5 Hz), 3.77–3.84 (m, 3H), 3.97 (dd, 1H, J = 5.0 Hz, 9.0 Hz), 5.47 (s, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 15.07, 25.21, 51.52, 55.46, 63.20, 63.28, 69.17, 79.40; HRMS (ESI) Anal. calcd for C₈H₁₄O₄S [M + Na]⁺: 229.0505, found: 229.0498.

Ethyl 2,3-anhydro-4,6-di-O-benzyl-1-thio-α-D-mannopyranoside (2). To a solution of 2d (210 mg, 1.02 mmol) in DMF (10 mL) was added Ag₂O (1.89 g, 8.17 mmol), KI (1.35 g, 8.17 mmol) and BnBr (0.91 mL, 7.69 mmol). After stirring for 8 h at room temperature, the reaction mixture was concentrated. The mixture was filtered and the filtrate was concentrated to give a residue that was purified by column chromatography on silica gel (petroleum ether–ethyl acetate, 12 : 1) to yield 2 (370 mg, 94%) as a colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 1.30 (t, 3H, J = 7.5 Hz), 2.64 (qd, 1H, J = 7.5 Hz, 13.0 Hz), 2.76 (qd, 1H, J = 7.5 Hz, 13.0 Hz), 3.21 (d, 1H, J = 3.5 Hz), 3.36 (d, 1H, J = 4.0 Hz), 3.58 (d, 1H, J = 3.0 Hz), 3.71 (d, 1H, J = 9.5 Hz), 4.00 (dt, 1H, J = 3.5 Hz, 9.5 Hz), 4.44 (d, 1H, J = 12.5 Hz), 4.46 (d, 1H, J = 12.0 Hz), 4.58 (d, 1H, J = 12.5 Hz), 4.70 (d, 1H, J = 11.5 Hz), 5.51 (s, 1H), 7.25–7.34 (m, 10H); ¹³C NMR (125 MHz, CDCl₃) δ 14.96, 24.84, 51.30, 53.45, 67.48, 68.94, 69.27, 72.19, 73.14, 79.25, 127.54, 127.72, 127.99, 128.26, 128.46, 137.29, 138.12; HRMS (ESI) Anal. calcd for C₂₂H₂₆O₄S [M + NH₄]⁺: 404.1890, found: 404.1892.

2-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-β-D-altropyranosyl)-5-methoxyphenol (4a). Compound 4a was isolated after column chromatography on silica gel (petroleum ether–ethyl acetate, 5 : 1) as a colorless oil (65% yield): R_f 0.30 (petroleum ether–ethyl acetate, 2 : 1); ¹H NMR (400 MHz, CDCl₃) δ 2.28 (s, 3H, tolyl CH₃), 2.63 (s, 1H, OH), 3.53 (t, 1H, J = 2.8 Hz, H-2), 3.69 (dd, 1H, J = 4.4 Hz, 10.4 Hz, H-6a), 3.75 (dd, 1H, J = 1.6 Hz, 10.4 Hz, H-6b), 3.77 (s, 3H, OCH₃), 3.98 (ddd, 1H, J = 2.0 Hz, 4.4 Hz, 10.0 Hz, H-5), 4.18 (dd, 1H, J = 2.8 Hz, 10.0 Hz, H-4), 4.33 (t, 1H, J = 2.8 Hz, H-3), 4.50 (d, 1H, J = 11.6 Hz, PhCH₂), 4.56 (d, 1H, J = 12.0 Hz, PhCH₂), 4.57 (d, 1H, J = 11.6 Hz, PhCH₂), 4.65 (d, 1H, J = 12.0 Hz, PhCH₂), 5.47 (d, 1H, J = 2.0 Hz, H-1), 6.38 (dd, 1H, J = 2.4 Hz, 8.4 Hz), 6.46 (d, 1H, J = 2.4 Hz), 6.83 (d, 1H, J = 8.8 Hz), 6.98 (d, 2H, J = 8.4 Hz), 7.01 (d, 2H, J = 8.4 Hz), 7.23–7.38 (m, 10H), 8.36 (s, 1H, ArOH); ¹³C NMR (125 MHz, CDCl₃) δ 21.03, 55.22, 57.22 (C-2), 68.07 (C-3), 68.93 (C-6), 71.31 (C-4), 72.02, 73.48, 75.23 (C-5), 77.25 (C-1), 102.35, 105.97, 114.56, 127.31, 127.66, 127.75, 128.15, 128.24, 128.45, 128.60, 129.70, 131.30, 132.27, 137.21, 137.38, 138.02, 157.80, 160.29; HRMS (ESI) Anal. calcd for C₃₄H₃₆O₆S [M + NH₄]⁺: 466.2047, found: 466.2049.

2-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-β-D-altropyranosyl)-4,5-dimethoxyphenol (4b). Compound 4b was isolated after column chromatography on silica gel (petroleum ether–ethyl acetate, 2 : 1) as a colorless oil (90% yield): R_f 0.30 (petroleum ether–ethyl acetate, 1 : 1); ¹H NMR (500 MHz, CDCl₃) δ 2.28 (s, 3H, tolyl CH₃), 2.67 (d, 1H, J = 1.0 Hz, OH), 3.55 (dd, 1H, J = 2.5 Hz, 3.5 Hz, H-2), 3.69 (s, 3H, OCH₃), 3.70 (dd, 1H, J = 4.5 Hz, 11.0 Hz, H-6a), 3.75 (dd, 2H, J = 2.5 Hz, 11.0 Hz, H-6b), 3.84 (s, 3H, OCH₃), 3.98 (ddd, 1H, J = 2.0 Hz, 4.5 Hz, 10.0 Hz, H-5), 4.16 (dd, 1H, J = 2.5 Hz, 10.0 Hz, H-4), 4.38 (t, 1H, J = 3.0 Hz, H-3), 4.51 (d, 1H, J = 11.5 Hz, PhCH₂), 4.55 (d, 1H, J = 12.0 Hz, PhCH₂), 4.58 (d, 1H, J = 11.5 Hz, PhCH₂), 4.65 (d, 1H, J = 12.5 Hz, PhCH₂), 5.43 (d, 1H, J = 2.0 Hz, H-1), 6.37 (s, 1H), 6.47 (s, 1H), 6.97–7.02 (m, 4H), 7.24–7.38 (m, 10H), 8.07 (s, 1H, ArOH); ¹³C NMR (125 MHz, CDCl₃) δ 20.99, 55.77, 56.58, 57.37 (C-2), 68.22 (C-3), 68.90 (C-6), 71.31 (C-4), 72.03, 73.48, 75.20 (C-5), 77.39 (C-1), 101.78, 109.97, 112.36, 127.66, 127.72, 128.14, 128.25, 128.44, 128.60, 129.66, 131.38, 132.26, 137.17, 137.44, 138.00, 142.06, 149.43, 150.91; HRMS (ESI) Anal. calcd for C₃₅H₃₈O₇S [M + Na]⁺: 625.2231, found: 625.2238.

2-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-α-D-altropyranosyl)-3,5-dimethoxyphenol (4c). Compound 4c was isolated after column chromatography on silica gel (petroleum ether–ethyl acetate, 6 : 1) as a colorless oil (65% yield): R_f 0.35 (petroleum ether–ethyl acetate, 2 : 1); [α]²⁰_D −84.4 (c 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 2.26 (s, 3H, tolyl CH₃), 2.63 (d, 1H, J = 6.5 Hz, OH), 3.52 (dd, 1H, J = 5.5 Hz, 10.5 Hz, H-6a), 3.62 (dd, 1H, J = 5.5 Hz, 10.5 Hz, H-6b), 3.67 (t, 1H, J = 10.5 Hz, H-2), 3.74 (s, 3H, OCH₃), 3.75–3.79 (m, 1H, H-3), 3.81 (s, 3H, OCH₃), 3.87 (t, 1H, J = 2.0 Hz, 3.0 Hz, H-4), 4.26–4.32 (m, 1H, H-5), 4.47 (s, 2H, PhCH₂), 4.73 (d, 1H, J = 12.0 Hz, PhCH₂), 4.76 (d, 1H, J = 12.0 Hz, PhCH₂), 5.33 (d, 1H, J = 11.0 Hz, H-1), 6.00 (d, 1H, J = 2.0 Hz), 6.02 (d, 1H, J = 2.5 Hz), 6.94 (d, 1H, J = 8.0 Hz), 7.14 (dd, 2H, J = 2.5 Hz, 6.0 Hz), 7.25–7.37 (m, 10H), 7.73 (s, 1H, ArOH); ¹³C NMR (125 MHz, CDCl₃) δ 21.05, 53.48 (C-2), 55.26, 55.55, 67.46 (C-6), 68.71 (C-3), 70.43 (C-1), 72.92, 73.39, 74.96 (C-5), 76.09 (C-4), 91.11, 94.72, 105.95, 127.54, 127.80, 127.91, 128.48, 128.58, 129.22, 129.43, 133.76, 137.60, 158.04, 158.25, 161.35; HRMS (ESI) Anal. calcd for C₃₅H₃₈O₇S [M + Na]⁺: 625.2231, found: 625.2238.

1-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-α-D-altropyranosyl)-2-naphthol (4d). Compound 4d was isolated after column chromatography on silica gel (petroleum ether–ethyl acetate, 5 : 1) as a colorless oil (71% yield): R_f 0.20 (petroleum ether–ethyl acetate, 3 : 1); [α]²⁰_D −40.0 (c 0.5, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 2.13 (s, 3H), 2.81 (d, 1H, J = 6.0 Hz), 3.76 (dd, 1H, J = 5.2 Hz, 10.4 Hz), 3.80 (dd, 1H, J = 5.2 Hz, 10.4 Hz), 3.96 (t, 1H, J = 10.8 Hz), 4.04 (t, 1H, J = 2.8 Hz), 4.07–4.12 (m, 1H), 4.34–4.37 (m, 1H), 4.55 (d, 1H, J = 12.0 Hz), 4.59 (d, 1H, J = 12.0 Hz), 4.83 (s, 2H), 5.79 (d, 1H, J = 10.8 Hz), 6.45 (d, 2H, J = 8.0 Hz), 6.63 (d, 2H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.8 Hz), 7.26–7.45 (m, 12H), 7.56 (d, 1H, J = 8.8 Hz), 7.66 (d, 1H, J = 7.6 Hz), 7.96 (d, 1H, J = 8.8 Hz), 8.05 (brs, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 20.87, 54.57, 68.43, 69.61, 73.07, 73.14, 73.62, 75.43, 76.13, 119.29, 122.73, 122.90, 126.00, 127.67, 127.90, 127.99, 128.00, 128.23, 128.64, 128.80, 129.00, 129.70, 130.19, 131.96, 132.74, 136.87, 137.46, 137.69; HRMS (ESI) Anal. calcd for C₃₅H₃₈O₇S [M + NH₄]⁺: 610.2622, found: 610.2645.

1-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-α-D-altropyranosyl)-7-methoxy-2-naphthol (4e). Compound 4e was isolated after column chromatography on silica gel (petroleum ether–ethyl acetate, 6 : 1) as a colorless oil (73% yield): R_f 0.35 (petroleum ether–ethyl acetate, 2 : 1); [α]²⁰_D −133.2 (c 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 2.12 (s, 3H, tolyl CH₃), 2.81 (d, 1H, J = 6.5 Hz, OH), 3.73 (s, 1H, OCH₃), 3.80 (dd, 1H, J = 4.5 Hz, 10.5 Hz, H-6a), 3.85 (dd, 1H, J = 4.5 Hz, 10.5 Hz, H-6b), 3.98 (t, 1H, J = 10.5 Hz, H-2), 4.07 (t, 1H, J = 2.5 Hz, H-4), 4.20 (ddd, 1H, J = 3.0 Hz, 6.0 Hz, 13.5 Hz, H-3), 4.32–4.34 (m, 1H, H-5), 4.56 (d, 1H, J = 12.0 Hz, PhCH₂), 4.60 (d, 1H, J = 12.0 Hz, PhCH₂), 4.82 (s, 2H, PhCH₂), 5.79 (d, 1H, J = 11.0 Hz), 6.52 (d, 2H, J = 8.0 Hz), 6.64 (d, 2H, J = 8.0 Hz), 6.80 (d, 1H, J = 8.5 Hz), 6.95 (dd, 1H, J = 2.0 Hz, 8.0 Hz), 7.26–7.43 (m, 11H), 7.48 (d, 1H, J = 8.5 Hz), 7.55 (d, 1H, J = 8.5 Hz), 8.08 (brs, 1H, ArOH); ¹³C NMR (125 MHz, CDCl₃) δ 20.87, 54.60 (C-2), 55.11, 69.37 (C-6), 69.74 (C-3), 73.14, 73.61 (C-1), 75.33 (C-5), 76.27 (C-4), 102.88, 114.60, 116.81, 127.27, 127.93, 128.04, 128.62, 128.65, 128.99, 129.68, 129.94, 131.81, 133.96, 136.82, 137.46, 137.64, 157.89; HRMS (ESI) Anal. calcd for C₃₈H₃₈O₆S [M + NH₄]⁺: 640.2727, found: 640.2714.

2-(4,6-Di-O-benzyl-2-deoxy-2-p-ethylthio-β-D-glucopyranosyl)-5-methoxyphenol (4f). Compound 4f was isolated after column chromatography on silica gel (petroleum ether–acetone, 5 : 1) as a colorless oil (81% yield): R_f 0.40 (petroleum ether–acetone, 2 : 1); [α]²⁰_D +78.4 (c 0.5, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 0.98 (t, 3H, J = 7.5 Hz, ethyl CH₃), 1.80–1.85 (m, 2H, ethyl CH₂), 2.87 (t, 1H, J = 10.5 Hz, H-2), 3.13 (d, 1H, J = 1.0 Hz, OH), 3.51–3.59 (m, 2H, H-3 and H-5), 3.68 (dd, 1H, J = 2.0 Hz, 10.0 Hz, H-6a), 3.76–3.84 (m, 5H, H-6b, OCH₃ and H-4), 4.36 (d, 1H, J = 11.0 Hz, H-1), 4.46 (d, 1H, J = 12.5 Hz, PhCH₂), 4.58 (d, 1H, J = 12.0 Hz, PhCH₂), 4.59 (d, 1H, J = 11.0 Hz, PhCH₂), 4.97 (d, 1H, J = 11.0 Hz, PhCH₂), 6.42 (dd, 1H, J = 2.5 Hz, 8.5 Hz), 6.47 (d, 1H, J = 2.5 Hz), 7.08 (d, 1H, J = 8.5 Hz), 7.25–7.34 (m, 10H), 7.86 (s, 1H, ArOH); ¹³C NMR (100 MHz, CDCl₃) δ 14.71, 26.28, 53.77 (C-2), 55.29, 68.04 (C-6), 73.46, 74.85, 75.57 (C-3), 77.39 (C-4), 78.01 (C-5), 83.48 (C-1), 102.82, 105.71, 115.56, 127.72, 127.76, 127.79, 128.10, 128.40, 128.43, 130.38, 137.92, 138.37, 156.97, 160.96; HRMS (ESI) Anal. calcd for C₂₉H₃₄O₆S [M + NH₄]⁺: 528.2414, found: 528.2430.

1-(4,6-Di-O-benzyl-2-deoxy-2-p-ethylthio-β-D-glucopyranosyl)-2-naphthol (4g). Compound 4g was isolated after column chromatography on silica gel (petroleum ether–acetone, 8 : 1) as a colorless oil (79% yield): R_f 0.35 (petroleum ether–acetone, 3 : 1); [α]²⁰_D +90.4 (c 0.3, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 0.67 (t, 3H, J = 7.5 Hz, ethyl CH₃), 1.41–1.59 (m, 2H, ethyl CH₂), 3.19 (d, 1H, J = 1.5 Hz, OH), 3.25 (t, 1H, J = 11.5 Hz, H-2), 3.66–3.73 (m, 3H, H-6a, H-3 and H-5), 3.82 (dd, 1H, J = 2.5 Hz, 10.0 Hz, H-6b), 3.94 (t, 1H, J = 9.0 Hz, H-4), 4.47 (d, 1H, J = 12.0 Hz, PhCH₂), 4.60 (d, 1H, J = 12.5 Hz, PhCH₂), 4.63 (d, 1H, J = 11.5 Hz, PhCH₂), 5.01 (d, 1H, J = 11.0 Hz, PhCH₂), 5.44 (d, 1H, J = 10.5 Hz, H-1), 7.16 (d, 1H, J = 9.0 Hz), 7.26–7.35 (m, 11H), 7.44–7.47 (m, 1H), 7.72–7.75 (m, 2H), 8.07 (d, 1H, J = 8.5 Hz), 8.50 (s, 1H, ArOH); ¹³C NMR (125 MHz, CDCl₃) δ 14.34, 26.23, 52.80 (C-2), 67.89 (C-6), 73.41, 74.91, 75.81 (C-3), 77.36 (C-4), 77.60 (C-1), 78.37 (C-5), 115.27, 119.66, 123.12, 123.16, 125.98, 127.73, 127.80, 128.13, 128.22, 128.42, 128.73, 130.49, 132.38, 137.86, 138.33, 154.69; HRMS (ESI) Anal. calcd for C₃₂H₃₄O₅S [M + NH₄]⁺: 548.2465, found: 548.2454.

3-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-α-D-altropyranosyl)-1-propene (6a). Compound 6a was isolated after column chromatography on silica gel (petroleum ether–acetone, 18 : 1) as a colorless oil (50% or 64% yield): R_f 0.35 (petroleum ether–ethyl acetate, 6 : 1); [α]²⁰_D −17.2 (c 0.5, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 2.32 (s, 3H, tolyl CH₃), 2.57–2.63 (m, 1H, CH₂CHCH₂), 2.65 (d, 1H, J = 4.5 Hz, OH), 2.75–2.80 (m, 1H, CH₂CHCH₂), 3.19 (t, 1H, J = 6.5 Hz, H-2), 3.50 (dd, 1H, J = 4.5 Hz, 10.5 Hz, H-6a), 3.55 (dd, 1H, J = 5.5 Hz, 10.5 Hz, H-6b), 3.76 (ddd, 1H, J = 4.5 Hz, 6.5 Hz, 8.0 Hz, H-1), 3.86–3.91 (m, 2H, H-3 and H-4), 4.09 (dd, 1H, J = 5.0 Hz, 9.5 Hz, H-5), 4.45 (d, 1H, J = 12.0 Hz, PhCH₂), 4.51 (d, 1H, J = 12.0 Hz, PhCH₂), 4.56 (d, 1H, J = 11.5 Hz, PhCH₂), 4.62 (d, 1H, J = 11.5 Hz, PhCH₂), 5.05–5.11 (m, 2H, =CH₂), 5.80–5.89 (m, 1H, –CH=), 7.09 (d, 2H, J = 8.0 Hz), 7.27–7.35 (m, 12H); ¹³C NMR (125 MHz, CDCl₃) δ 21.11, 37.14, 51.97 (C-2), 68.19 (C-3), 69.02 (C-6), 71.18 (C-5), 72.03, 73.32, 74.36 (C-4), 74.73 (C-1), 117.05, 127.65, 127.90, 127.95, 128.35, 128.47, 129.16, 129.81, 133.53, 134.92, 137.80, 137.93, 138.04; HRMS (ESI) Anal. calcd for C₃₀H₃₄O₄S [M + NH₄]⁺: 508.2516, found: 508.2518.

2-(4,6-Di-O-benzyl-2-deoxy-2-p-tolylthio-α-D-altropyranosyl)-cyclopentone (6b). Compound 6b was isolated after column chromatography on silica gel (petroleum ether–acetone, 10 : 1) as a colorless oil (51% yield): R_f 0.30 (petroleum ether–acetone, 5 : 1); [α]²⁰_D −42.0 (c 0.2, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 1.67–1.71 (m, 1H), 1.83–1.88 (m, 1H), 1.96–2.05 (m, 2H), 2.08–2.15 (m, 1H), 2.28 (t, 1H, J = 8.5 Hz), 2.32 (s, 3H), 2.72 (d, 1H, J = 6.0 Hz), 3.11 (td, 1H, J = 3.5 Hz, 9.0 Hz), 3.26 (t, 1H, J = 9.0 Hz), 3.47 (d, 2H, J = 6.0 Hz), 3.79 (qd, 1H, J = 3.5 Hz, 6.0 Hz, 9.5 Hz), 3.86 (t, 1H, J = 3.5 Hz), 4.01 (dd, 1H, J = 4.0 Hz, 9.0 Hz), 4.05 (td, 1H, J = 3.5 Hz, 5.5 Hz), 4.41 (d, 1H, J = 12.0 Hz, PhCH₂), 4.45 (d, 1H, J = 12.0 Hz, PhCH₂), 4.57 (d, 1H, J = 12.0 Hz, PhCH₂), 4.65 (d, 1H, J = 12.0 Hz, PhCH₂), 7.10 (d, 2H, J = 8.0 Hz), 7.26–7.36 (m, 10H), 7.38 (d, 2H, J = 8.0 Hz); ¹³C NMR (125 MHz, CDCl₃) δ 20.59, 21.15, 23.35, 39.19, 50.52, 51.33, 68.01, 68.78, 71.90, 72.47, 73.40, 73.63, 75.40, 127.58, 127.62, 127.77, 127.83, 128.07, 128.38, 128.46, 129.86, 134.36, 137.93, 138.33, 219.69; HRMS (ESI) Anal. calcd for C₃₂H₃₆O₅S [M + NH₄]⁺: 550.2622, found: 550.2627.

3-(4,6-Di-O-benzyl-2-deoxy-2-p-ethylthio-β-D-glucopyranosyl)-1-propene (6c). Compound 6c was isolated after column chromatography on silica gel (petroleum ether–acetone, 15 : 1) as a colorless oil (46% or 41% yield): R_f 0.35 (petroleum ether–acetone, 5 : 1); ¹H NMR (500 MHz, CDCl₃) δ 1.28 (t, 3H, J = 7.5 Hz, ethyl CH₃), 2.37–2.42 (m, 2H, H-2 and CH₂CHCH₂), 2.55–2.67 (m, 2H, ethyl CH₂), 2.78–2.83 (m, 1H, CH₂CHCH₂), 3.02 (d, 1H, J = 1.5 Hz, OH), 3.33 (ddd, 1H, J = 3.0 Hz, 8.0 Hz, 10.5 Hz, H-1), 3.39 (ddd, 1H, J = 2.0 Hz, 4.5 Hz, 9.5 Hz, H-5), 3.49 (t, 1H, J = 8.5 Hz, 9.5 Hz, H-4), 3.54–3.58 (m, 1H, H-3), 3.69 (dd, 1H, J = 4.5 Hz, 11 Hz, H-6b), 3.74 (dd, 1H, J = 2.0 Hz, 10.5 Hz, H-6a), 4.57 (d, 1H, J = 12.5 Hz, PhCH₂), 4.61 (d, 1H, J = 11.0 Hz, PhCH₂), 4.63 (d, 1H, J = 12.5 Hz, PhCH₂), 4.91 (d, 1H, J = 11.5 Hz, PhCH₂), 5.09–5.15 (m, 2H, =CH₂), 5.91–5.99 (m, 1H, –CH=), 7.26–7.35 (m, 10H); ¹³C NMR (125 MHz, CDCl₃) δ 15.29, 25.03, 36.91, 53.75 (C-2), 69.17 (C-6), 73.40, 74.60, 76.15 (C-3), 78.55 (C-4, C-5), 78.96 (C-1), 117.10, 127.51, 127.71, 127.99, 128.31, 128.38, 134.78, 138.47; HRMS (ESI) Anal. calcd for C₂₅H₃₂O₄S [M + NH₄]⁺: 446.2359, found: 446.2357.

2-(4,6-Di-O-benzyl-2-deoxy-2-p-ethylthio-β-D-glucopyranosyl)-cyclopentone (6d). Compound 6d was isolated after column chromatography on silica gel (petroleum ether–acetone, 10 : 1) as a colorless oil (70% yield): R_f 0.30 (petroleum ether–acetone, 5 : 1); [α]²⁰_D −23.2 (c 1.7, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 1.26 (t, 3H, J = 7.5 Hz, ethyl CH₃), 1.73–1.84 (m, 1H), 2.00–2.15 (m, 4H), 2.28–2.34 (m, 1H), 2.42 (t, 1H, J = 10.5 Hz, H-2), 2.55–2.66 (m, 2H, ethyl CH₂), 2.86 (dd, J = 9.0 Hz, 1H), 2.97 (d, 1H, J = 1.5 Hz, OH), 3.39 (ddd, 1H, J = 2.0 Hz, 4.0 Hz, 9.5 Hz, H-5), 3.54 (dd, 1H, J = 9.0 Hz, 10.0 Hz, H-4), 3.61–3.67 (m, 2H, H-3, H-6a), 3.72 (dd, 1H, J = 4.0 Hz, 11.5 Hz, H-6b), 3.87 (dd, 1H, J = 2.0 Hz, 11.0 Hz, H-1), 4.50 (d, 1H, J = 12.5 Hz, PhCH₂), 4.54 (d, 1H, J = 12.0 Hz, PhCH₂), 4.66 (d, 1H, J = 11.0 Hz, PhCH₂), 4.89 (d, 1H, J = 11.0 Hz, PhCH₂), 7.27–7.33 (m, 10H); ¹³C NMR (125 MHz, CDCl₃) δ 15.09, 20.84, 22.76, 23.46, 39.07, 50.19, 51.42 (C-2), 68.94 (C-6), 73.16, 74.61, 75.56 (C-3), 77.19 (C-1), 78.35 (C-5), 78.47 (C-4), 127.47, 127.70, 127.98, 128.26, 128.39, 138.47, 219.58; HRMS (ESI) Anal. calcd for C₂₇H₃₄O₅S [M + NH₄]⁺: 488.2465, found: 488.2474.

2-(4,6-Di-O-benzyl-2-deoxy-β-D-altropyranosyl)-4,5-di-methoxy-phenol (7). Compound 7 was isolated after column chromatography on silica gel (toluene–CH₃CN, 6 : 1) as a colorless oil (72% yield): R_f 0.40 (toluene–CH₃CN, 4 : 1); ¹H NMR (400 MHz, CDCl₃) δ 1.99–2.06 (m, 1H), 2.18 (dd, 1H, J = 3.2 Hz, 12.0 Hz), 2.49 (s, 1H), 3.71 (d, 2H, OCH₃, J = 2.4 Hz), 3.75 (d, 1H, J = 2.4 Hz), 3.78 (s, 1H), 3.83 (s, 1H), 3.98 (d, 1H, J = 10.0 Hz), 4.31 (d, 1H, J = 2.0 Hz), 4.47–4.51 (m, 2H), 4.59–4.62 (m, 2H), 5.00 (dd, 1H, J = 2.0 Hz, 11.6 Hz, H-1), 6.49 (s, 1H), 6.50 (s, 1H), 7.24–7.31 (m, 10H), 7.93 (s, 1H, OH); ¹³C NMR (125 MHz, CDCl₃) δ 36.97, 55.85, 56.61, 64.30, 68.70, 71.79, 73.44, 73.69, 74.01, 74.49, 102.13, 110.36, 115.70, 127.70, 127.78, 127.99, 128.21, 128.42, 128.60, 137.35, 137.98, 142.14, 149.40, 149.97; HRMS (ESI) Anal. calcd for C₂₈H₃₂O₇ [M + H]⁺: 481.2221, found: 481.2232.

Acknowledgements

This work was financially supported by the grants (2012ZX09502001-001, 2012CB822100) from the Ministry of Science and Technology of China, the National Natural Science Foundation of China (grant no. 21232002, 21102008), Beijing Natural Science Foundation (2142015) and Beijing Higher Education Young Elite Teacher Project (YETP0063).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Copies of NMR spectra of 1, 1b, 2c, 2d, 2, 4a–4g, 6a–6d, 7. See DOI: 10.1039/c4qo00113c

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