Nabamita Basu, Sajal Kumar Maity, Rina Ghosh* - rsc.org · Nabamita Basu, Sajal Kumar Maity, Rina Ghosh* Department of Chemistry, Jadavpur University, Kolkata 700 032, India. Fax:

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SUPPORTING INFORMATION

Trichloroisocyanuric acid (TCCA) – TMSOTf: An efficient activator system for glycosylation reactions based on thioglycosides

Nabamita Basu, Sajal Kumar Maity, Rina Ghosh*

Department of Chemistry, Jadavpur University, Kolkata 700 032, India. Fax: +91-33-2414-6266

E-mail: [email protected]; [email protected]

Table of Contents

Experimental S-2-18

References S-18 1H NMR of 3 S-19 13C NMR of 3 S-20

COSY spectra of 3 S-21

HSQC spectra of 3 S-22 1H NMR of 6 S-23 13C NMR of 6 S-24 1H NMR of 12 S-25 13C NMR of 12 S-26


HSQC spectra of 12 S-28 1H NMR of 30 S-29 13C NMR of 30 S-30


HSQC spectra of 30 S-32

Electronic Supplementary Material (ESI) for RSC AdvancesThis journal is © The Royal Society of Chemistry 2012

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Experimental

General Procedure

All reactions were done in argon atmosphere. All glasswares were stored in the oven and

were flame-dried prior to use. Dry CH2Cl2 was obtained by distillation over P2O5. All reagents

and solvents were commercially available. Reagents were used without further purification and

solvents were distilled prior to use. Column chromatography and flash column chromatography

were performed using 60-120 and 230-400 mesh silica, respectively. Petroleum ether (PE, 60-

80ºC) was used for chromatographic purpose. Melting points were recorded in Toshniwal

melting point apparatus and are uncorrected. NMR spectra were recorded on Bruker DPX NMR

spectrometer operating at 300 MHz and 500 MHz for 1H-NMR and at 75 MHz and 125 MHz for 13C-NMR in CDCl3. Assignments were obtained using 1H -1H COSY, and 1H -13C HSQC

experiments. HRMS data were recorded on a Q-tof-Micro mass spectrometer by electron spray

ionization method. Specific rotations were measured on Jasco J-815 spectrometer. Rotations

were determined using a cell of 1 dm-path length. Data are reported as follows: [α]D temp,

concentration (c in g/100 mL) and solvent.

Methyl (2,3-di-O-benzoyl-4,6-O-benzylidene-β-D-glucopyranosyl)-(1→6)-2,3,4-tri-O-

benzoyl-α-D-glucopyranoside (3)

To a mixture of 1 (105 mg, 0.18 mmol) and 2 (76 mg, 0.15 mmol) in dry CH2Cl2 (5 mL), flame

activated 4Å molecular sieves were added. It was stirred at room temperature under argon

atmosphere. After 40 mins the mixture was cooled to -5ºC and TCCA (35 mg, 0.15 mmol) was

added to it. Then TMSOTf (8.2 µL, 0.05 mmol) was added via a micro-syringe. After the

acceptor was consumed completely (checked by TLC) the reaction was quenched by

triethylamine (80 µL). Molecular sieves were filtered off through celite bed. The filtrate was

diluted with CH2Cl2 and washed subsequently with saturated NaHCO3 solution and water. The

OSTol

OBz

OBzO

OPh

1

O

OMeBzO

BzOBzO

HO

2O

OBz

OBzO

OPh

O

OMeBzO

BzOBzO

O

3TCCA, TMSOTf

CH2Cl2


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organic layer was dried over anhydrous Na2SO4 and concentrated to afford the glycosylated

product. The crude mass was purified by silica gel column chromatography (60-120 mesh)

(PE/EtOAc 5:1) to get pure product (3, 137.6 mg) in 95% yield.

Scale-up (~13 fold) experimental procedure for preparation of 3

The scale-up experiment was done following the above reaction procedure using 1 (1.38 g, 2.37

mmol), 2 (1 g, 1.98 mmol), 4Å molecular sieves, TCCA (460.1 mg, 1.98 mmol) and TMSOTf

(107.5 µL, 0.59 mmol) in dry CH2Cl2 (30 ml). After completion the reaction was quenched by

triethylamine (1.08 mL). Pure chromatographed product (3, 1.79 g) was obtained as before in

94% yield. It was crystallized from PE/EtOAc; mp 232-234 ºC.

[α]25D +38.8 (c 1.39, CHCl3).

1H NMR (CDCl3, 300 MHz): δ 3.12 (s, 3H, OCH3), 3.66-3.83 (m, 3H), 3.90 (apparent t, J = 9.4,

9.7 Hz, 1H), 4.08 (d, J = 10.9 Hz, 1H), 4.21 (apparent t, J = 8.0, 9.3 Hz, 1H), 4.42 (dd, J = 4.6,

10.2 Hz, 1H), 4.92 (d, J = 4.1 Hz, 1H, 1-H), 4.93 (d, J = 7.3 Hz, 1H, 1-H’), 5.11 (dd, J = 3.5,

10.2 Hz, 1H), 5.33 (m, 1H), 5.48-5.58 (m, 2H, CHPh), 5.81 (t, J = 9.5 Hz, 1H), 6.08 (t, J = 9.8

Hz, 1H), 7.24-7.44 (m, 16H, ArH), 7.47-7.54 (m, 4H, ArH), 7.79-7.82 (m, 2H, ArH), 7.89-7.99

(m, 8H, ArH). 13C NMR (75 MHz, CDCl3): δ 55.0, 66.6, 68.5, 68.6, 69.0, 69.6, 70.3, 71.9, 72.0, 72.4, 78.7,

96.4 (1-C), 101.4 (CHPh), 102.0 (1-C'), 126.1, 128.16, 128.19, 128.26, 128.29, 128.33, 128.4,

129.0, 129.3, 129.6, 129.77, 129.84, 133.0, 133.1, 133.2, 133.4, 136.7, 165.3 (C=O), 165.4

(C=O), 165.6 (C=O), 165.7 (C=O).

HRMS m/z calcd for (C55H48O16Na+) calcd: 987.2840, found: 987.2841.

3-(N-Carboxybenzyl) propyl 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranoside (6)

A mixture of 4 (201.0 mg, 0.286 mmol), 5 (50.0 mg, 0.238 mmol) and flame activated 4Å

molecular sieves in dry CH2Cl2 (4 mL) were stirred at room temperature under argon

atmosphere. After 40 min the mixture was cooled to -5ºC and TCCA (55.3 mg, 0.238 mmol)


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followed by TMSOTf (12.9 µL, 0.071 mmol) were added to it. The reaction mixture was

warmed gradually to room temperature. After the acceptor was consumed completely (checked

by TLC) the reaction was quenched by triethylamine (130 µL). Molecular sieves were filtered

off through celite bed. The filtrate was diluted with CH2Cl2 and washed subsequently with

saturated NaHCO3 (50 mL) solution and water (50 mL). The organic layer was dried over

anhydrous Na2SO4 and concentrated to afford the glycosylated product. The crude product was

purified by column chromatography on silica gel (60-120 mesh) using PE:EtOAc 6:1 to give 6

(169.4 mg) in 90% as white foam.

[α]25D +60.05 (c 1.28, CHCl3).

1H NMR (CDCl3, 500 MHz): δ 1.77-1.88 (m, 2H), 3.15-3.27 (m, 2H), 3.67 (m, 1H), 4.03 (m,

1H), 4.32 (t, J = 6.5 Hz, 1H), 4.42 (dd, J = 6.8, 11.8 Hz, 1H), 4.67 (dd, J = 6.5, 11.5 Hz, 1H),

4.81 (d, J = 7.5 Hz, 1H, 1-H), 5.00 (m, 1H), 5.05 (s, 2H), 5.62 (dd, J = 3.8, 10.3 Hz, 1H), 5.78

(dd, J = 8.3, 10.3 Hz, 1H), 5.99 (d, J = 3.5 Hz, 1H), 7.21-7.26 (m, 2H, ArH), 7.29 (m, 1H, ArH),

7.33-7.36 (m, 6H, ArH), 7.41-7.44 (m, 3H, ArH), 7.46-7.51 (m, 3H, ArH), 7.55 (t, J = 7.5 Hz,

1H, ArH), 7.62 (t, J = 7.5 Hz, 1H, ArH), 7.77-7.79 (d, J = 8.0 Hz, 2H, ArH), 7.94-7.95 (d, J =

8.0 Hz, 2H, ArH), 8.00-8.02 (m, 2H, ArH), 8.08-8.09 (d, J = 8.0 Hz, 2H, ArH). 13C NMR (125 MHz, CDCl3): δ 29.7, 38.3, 62.2, 66.6, 68.3, 70.0, 71.6, 71.7, 101.8 (1-C),

128.1, 128.4, 128.6, 128.8, 128.9, 129.2, 129.4, 129.6, 129.8, 129.9, 130.2, 133.4, 133.5, 133.7,

156.6 (C=O), 165.7 (C=O), 166.2 (C=O).

HRMS m/z calcd for (C45H41NO12Na+) calcd: 810.2527, found: 810.2526.

3-(N-Carboxybenzyl) propyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranoside

(8)1

To a mixture of 7 (150.0 mg, 0.285 mmol) and 5 (50.0 mg, 0.238 mmol) in dry CH2Cl2 (5 mL),

flame activated 4Å molecular sieves were added. It was stirred at room temperature under argon

atmosphere. After 40 mins the mixture was cooled to -5ºC and TCCA (55.3 mg, 0.238 mmol)

was added to it. Then TMSOTf (12.9 µL, 0.071 mmol) was added via a micro-syringe. After the


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triethylamine (130.0 µL). Molecular sieves were filtered off through celite bed. The filtrate was

diluted with CH2Cl2 and washed subsequently with saturated NaHCO3 solution and water. The

organic layer was dried over anhydrous Na2SO4 and concentrated to afford the glycosylated

product. The crude product was purified by column chromatography on silica gel (60-120 mesh)

(PE:EtOAc 4:1) to afford 8 (128.7 mg) in 86% as white foam. 1H (300 MHz, CDCl3): δ 1.68-1.70 (m, 2H), 1.85 (s, 3H, COCH3), 2.03 (s, 3H, COCH3), 2.07 (s,

3H, COCH3), 3.04-3.16 (m, 2H), 3.55 (m, 1H), 3.82-3.89 (m, 2H), 4.19 (dd, J = 2.1, 12.2 Hz,

1H), 4.22-4.34 (m, 2H), 4.95 (m, 1H), 5.01 (s, 2H), 5.16 (t, J = 9.6 Hz, 1H), 5.38 (d, J = 8.5 Hz,

1H), 5.75 (dd, J = 9.1, 10.7 Hz, 1H), 7.30-7.35 (m, 5H, ArH), 7.70-7.73 (m, 2H, ArH), 7.81-7.83

(m, 2H, ArH). The spectral data were consistent with those in the literature.1

Methyl (2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-(1→6)-2,3,4-tri-O-benzoyl-α-D-

glucopyranoside (10)2

To a mixture of 9 (53.83 mg, 0.118 mmol) and 2 (50 mg, 0.099 mmol) in dry CH2Cl2 (3 mL),



was added to it. Then TMSOTf (5.3 µL, 0.029 mmol) was added via a micro-syringe. The

reaction mixture was warmed to room temperature quickly. After the acceptor was consumed

completely (checked by TLC) the reaction was quenched by triethylamine (53.0 µL). Molecular

sieves were filtered off through celite bed. The filtrate was diluted with CH2Cl2 and washed

subsequently with saturated NaHCO3 solution and water. The organic layer was dried over

anhydrous Na2SO4 and concentrated to afford the glycosylated product. This was then purified

by column chromatography on silica gel (60-120 mesh) using PE:EtOAc 4:1 to afford 10 (70.2

mg) in 85% yield as colorless syrup.


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1H (300 MHz, CDCl3): δ 2.01 (s, 9H, 3×COCH3), 2.09 (s, 3H, COCH3), 3.45 (s, 3H, OCH3),

3.65-3.73 (m, 2H), 4.02-4.09 (m, 2H), 4.21-4.28 (m, 2H), 4.58 (d, J = 7.9 Hz, 1H), 5.01-5.09 (m,

2H), 5.18-5.25 (m, 3H), 5.42 (t, J = 9.9 Hz, 1H), 6.13 (t, J = 9.3 Hz, 1H), 7.26-7.30 (m, 2H,

ArH), 7.35-7.44 (m, 5H, ArH), 7.48-7.55 (m, 2H, ArH), 7.83-7.85 (m, 2H, ArH), 7.95-7.98 (m,

4H, ArH). The spectral data were consistent with those in the literature.2

Methyl (3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl)-(1→6)-2,3,4-tri-O-

benzoyl-α-D-mannopyranoside (12)




followed by TMSOTf (5.3 µL, 0.029 mmol) were added to it. The reaction mixture was warmed

gradually to room temperature. After the acceptor was consumed completely (checked by TLC)

the reaction was quenched by triethylamine (53.0 µL). Molecular sieves were filtered off through

celite bed. The filtrate was diluted with CH2Cl2 and washed subsequently with saturated

NaHCO3 (50 mL) solution and water (50 mL). The organic layer was dried over anhydrous

Na2SO4 and concentrated to afford the glycosylated product. The crude product was purified by

flash chromatography on silica gel (230-400 mesh) using PE:EtOAc 3:2 to give 12 (81.0 mg) in

90% as white foam.

[α]25D -71.9 (c 1.35, CHCl3).

1H NMR (CDCl3-CCl4, 500 MHz) δ: 1.87 (s, 3H, COCH3), 2.02 (s, 3H, COCH3), 2.05 (s, 3H,

COCH3), 3.18 (s, 3H, OCH3), 3.65 (dd, J = 8.0, 11.0 Hz, 1H) 3.85 (m, 1H), 4.08-4.12 (m, 3H),

4.30 (dd, J = 4.8, 12.3 Hz, 1H), 4.34-4.38 (m, 2H, 1-H), 5.13 (dd, J = 9.5, 10.0 Hz, 1H), 5.40 (d,

J = 8.5 Hz, 1H, 1-H'), 5.45 (m, 1H), 5.55 (t, J = 10.0 Hz, 1H), 5.70 (dd, J = 3.5, 10.0 Hz, 1H),

5.78 (dd, J = 9.0, 10.5 Hz, 1H), 7.18-7.21 (m, 2H, ArH), 7.33-7.38 (m, 3H, ArH), 7.49-7.58 (m,


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4H, ArH), 7.64-7.65 (m, 2H, ArH), 7.69-7.71 (m, 4H, ArH), 7.80-7.82 (m, 2H, ArH), 8.04-8.06

(m, 2H). 13C NMR (125 MHz, CDCl3-CCl4) δ: 20.4, 20.6, 20.7, 54.5, 54.9, 61.9, 67.0, 68.9, 69.1, 69.6,

69.7, 70.2, 70.6, 72.0, 98.1 (1-C), 98.9 (1-C'), 123.3, 128.2, 128.4, 128.7, 128.9, 129.1, 129.4,

129.65, 129.74, 130.0, 133.0, 133.4, 133.5, 133.9, 165.1 (C=O), 165.2 (C=O), 165.3 (C=O),

169.3 (C=O), 169.9 (C=O), 170.4 (C=O).

HRMS m/z calcd for (C48H45NO18Na+) calcd: 946.2534, found: 946.2533.

13

OOAc

SPh

AcOAcO

AcO

O

OMeBnO

OBnO

OBn

TCCA, TMSOTf

CH2Cl2

14

O

OMeBnO

HOBnO

OBn

OOAc

AcOAcO

AcO

15

Methyl (2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-α-D-





added to it followed by TMSOTf (5.3 µL, 0.098 mmol) via a micro-syringe. Then the reaction

mixture was warmed to room temperature quickly. After the acceptor was consumed completely

(checked by TLC) the reaction was quenched by triethylamine (53.0 µL). Molecular sieves were

filtered off through celite bed. The filtrate was diluted with CH2Cl2 and washed subsequently

with saturated NaHCO3 solution and water. The organic layer was dried over anhydrous Na2SO4

and concentrated to afford the glycosylated product. This was purified by silica gel (60-120

mesh) column chromatography (PE/EtOAc 4:1) to afford 15 (69.4 mg) in 89% as colorless

syrup.

1H (300 MHz, CDCl3): δ 1.94 (s, 3H, COCH3), 1.95 (s, 3H, COCH3), 2.02 (s, 3H, COCH3),

2.03 (s, 3H, COCH3), 3.40 (s, 3H, OCH3), 3.53 (dd, J = 3.5, 9.6 Hz, 1H), 3.70-3.71 (m, 2H),

3.77-3.80 (m, 2H), 3.85 (dd, J = 2.1, 12.2 Hz, 1H), 3.89-4.00 (m, 2H), 4.13 (dd, J = 4.4, 12.2 Hz,

1H), 4.52-4.60 (m, 4H), 4.64-4.73 (m, 2H), 5.04 (d, J = 11.2 Hz, 1H), 5.16-5.29 (m, 3H), 5.36 (s,

1H), 7.23-7.33 (m, 15H, ArH). The spectral data were consistent with those in the literature.3


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Methyl (2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-(1→3)-2-O-benzyl-4,6-O-benzylidene

-α-D-glucopyranoside (18)4




added followed by TMSOTf (7.0 µL, 0.039 mmol) via a micro-syringe. Then reaction mixture

was warmed to room temperature quickly. After the acceptor was consumed completely




and concentrated to afford the glycosylated product, which was purified by column

chromatography on silica gel (60-120 mesh) using PE/EtOAc 4:1 to afford 18 (70.7 mg) in 73%

as white solid. 1H (300 MHz, CDCl3): δ 1.72 (s, 3H, COCH3), 1.92 (s, 3H, COCH3), 2.04 (s, 3H, COCH3), 2.07

(s, 3H, COCH3), 3.41 (s, 3H, OCH3), 3.78-3.96 (m, 6H), 4.34 (dd, J = 3.9, 9.9 Hz, 1H), 4.45 (t, J

= 9.4 Hz, 1H), 5.01 (d, J = 3.6 Hz, 1H), 5.07-5.18 (m, 2H), 5.22 (dd, J = 3.7 Hz, 1H), 5.34-5.36

(m, 2H), 5.60 (s, 1H, CHPh), 7.32-7.33 (m, 3H, ArH), 7.40-7.43 (m, 2H, ArH), 7.45-7.50 (m,

2H, ArH), 7.60 (apparent t, J = 6.5, 7.0 Hz, 1H, ArH), 8.07-8.10 (d, J = 8.1 Hz, 2H, ArH). The

spectral data were consistent with those in the literature.4


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Methyl (2,3,4-tri-O-acetyl-α-L-rhamanopyranosyl)-(1→3)-2-O-benzyl-4,6-O-benzylidene-α-

D-glucopyranoside (20)5




added to it. Then TMSOTf (7.0 µL, 0.039 mmol) was added via a micro-syringe. The reaction




with saturated NaHCO3 solution and water, dried over anhydrous Na2SO4. The organic layer was

concentrated to afford glycosylated product. The crude product was purified by silica gel (60-120

mesh) column chromatography (PE/EtOAc 5:1) to afford 20 (69.0 mg) in 81% as white solid. 1H (300 MHz, CDCl3): δ 0.75 (d, J = 6.2 Hz, 3H, CH3), 1.89 (s, 3H, COCH3), 1.91 (s, 3H,

COCH3), 1.93 (s, 3H, COCH3), 3.38 (s, 3H, OCH3), 3.72 (t, J = 9.4 Hz, 1H), 3.82 (t, J = 10.2 Hz,

1H), 3.94 (m, 1H), 4.16 (m, 1H), 4.34 (dd, J = 4.5, 10.0 Hz, 1H), 4.42 (apparent t, J = 9.3, 11.6

Hz, 1H), 4.89 (t, J = 10.0 Hz, 1H), 5.00 (s,1H), 5.04-5.09 (m, 3H), 5.22 (dd, J = 3.5, 10.0 Hz,

1H), 5.59 (s, 1H, CHPh), 7.29-7.59 (m, 8H, ArH), 7.98-8.01 (m, 2H, ArH). The spectral data

were consistent with those in the literature.5

Methyl (2,3,4-tri-O-acetyl-α-L-rhamanopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-α-D-






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was added followed by TMSOTf (5.2 µL, 0.028 mmol) via a micro-syringe. Then reaction



filtered off through celite bed. The filtrate was diluted with CH2Cl2 and washed with saturated

NaHCO3 solution and water. The organic layer was dried over anhydrous Na2SO4 and

concentrated to afford the glycosylated product. This was purified by column chromatography

(PE/EtOAc 5:1) on silica gel (60-120 mesh) to afford 21 (63.5 mg 90%) as colorless syrup. 1H (300 MHz, CDCl3): δ 0.77 (d, J = 6.2 Hz, 3H, CH3), 1.98 (s, 3H, COCH3), 1.99 (s, 3H,

COCH3), 2.06 (s, 3H, COCH3), 3.36 (s, 3H, OCH3), 3.56-3.61 (m, 2H), 3.67 (m, 1H), 3.72-3.75

(m, 2H), 3.83-3.91 (m, 2H), 4.04 (m, 1H), 4.47-4.52 (m, 2H), 4.56-4.62(m, 2H), 4.68-4.75 (m,

2H), 4.93-5.01 (m, 2H), 5.09-5.16 (m, 2H), 5.25 (dd, J = 3.3, 10.1 Hz, 1H), 7.24-7.39 (m, 15H,

ArH). The spectral data were consistent with those in the literature.3

Methyl (3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-

benzyl-α-D-glucopyranoside (22)6




followed by TMSOTf (5.0 µL, 0.028 mmol) were added to it. After the acceptor was consumed




anhydrous Na2SO4 and concentrated to afford the glycosylated product, which was purified by

column chromatography (PE/EtOAc 2:1) on silica gel (60-120 mesh) to afford 22 (71.8 mg) in

88% as colorless syrup.


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1H (300 MHz, CDCl3): δ 1.82 (s, 3H, COCH3), 1.97 (s, 3H, COCH3), 1.98 (s, 3H, COCH3), 3.26

(s, 3H, OCH3), 3.80 (m, 1H), 3.90 (d, J = 9.2 Hz, 1H), 3.98 (t, J = 9.3 Hz, 1H), 4.07 (dd, J = 3.8,

12.4 Hz, 1H), 4.25 (dd, J = 8.4, 10.7 Hz, 1H), 4.34 (s, 2H), 4.49 (d, J = 3.6 Hz, 1H), 4.54 (d, J =

19.5 Hz, 1H), 4.68 (d, J = 12.1 Hz, 1H), 4.91 (d, J = 11.8Hz, 1H), 4.99 (d, J = 11.8 Hz, 1H), 5.11

(apparent t, J = 9.4, 9.8 Hz, 1H), 5.65 (m, 2H), 7.21-7.44 (m, 15H, ArH), 7.67-7.71 (m, 2H,

ArH), 7.80-7.83 (m, 2H, ArH). The spectral data were consistent with those in the literature.6

Methyl (2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-(1→6)-2,3,4-tri-O-benzoyl-α-D-





and TMSOTf (5.3 µL, 0.029 mmol) were added to it. Then reaction mixture was warmed to

room temperature quickly. After the acceptor was consumed completely (checked by TLC) the

reaction was quenched by triethylamine (53.0 µL). Molecular sieves were filtered off through

Celite bed. The filtrate was diluted with CH2Cl2 and washed subsequently with saturated

NaHCO3 solution and water. The organic layer was dried over anhydrous Na2SO4 and

concentrated to afford glycosylated product. This was purified by column chromatography

(PE:EtOAc 4:1) on silica gel (60-120 mesh) to afford 23 (68.6 mg) in 83% as colorless syrup. 1H (300 MHz, CDCl3): δ 1.99 (s, 3H, COCH3), 2.04 (s, 3H, COCH3), 2.05 (s, 3H, COCH3),

2.14 (s, 3H, COCH3), 3.50 (s, 3H, OCH3), 3.64 (dd, J = 2.1, 10.8 Hz, 1H), 3.89 (dd, J = 6.4, 10.8

Hz), 3.99-4.10 (m, 2H), 4.18 (dd, J = 5.1, 11.8 Hz, 1H), 4.25-4.30 (m, 1H), 4.84 (s, 1H), 5.22-

5.29 (m, 4H), 5.37 (dd, J = 3.3, 10.0 Hz, 1H), 5.53 (apparent t, J = 9.8, 10.0 Hz, 1H), 6.16 (t, J =

9.6 Hz, 1H), 7.29-7.52 (m, 9H, ArH), 7.85-7.99 (m, 6H, ArH). The spectral data were consistent

with those in the literature.2


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Methyl (2,3,4,6-tetra-O-acetyl-β-D-galacopyranosyl)-(1→3)-2-O-benzyl-3, 4-O-benzylidene

-α-D-glucopyranoside (25)7




added to it. Then TMSOTf (7.0 µL, 0.039 mmol) was added via a micro-syringe. The reaction





and concentrated to afford glycosylated product which was purified by column chromatography

on silica gel (60-120 mesh) using PE/EtOAc 4:1 to afford 25 (74.2 mg) in 80% yield as white

foam. 1H (300 MHz, CDCl3): δ 1.59 (s, 3H, COCH3), 1.88 (s, 3H, COCH3), 1.99 (s, 3H, COCH3), 2.09

(s, 3H, COCH3), 3.38 (s, 3H, OCH3), 3.74 (t, J = 9.1 Hz, 1H), 3.82-3.92 (m, 3H), 4.03 (dd, J =

5.9, 11.0 Hz, 1H), 4.12 (dd, J = 7.7, 11.0 Hz, 1H), 4.30 (dd, J = 3.9, 9.5 Hz, 1H), 4.38 (t, J = 9.4

Hz, 1H), 4.75 (d, J = 8.0 Hz, 1H), 4.83 (dd, J = 3.4, 10.4 Hz, 1H), 5.03 (d, J = 3.8 Hz, 1H), 5.12

(dd, J = 3.8, 9.6 Hz, 1H), 5.19 (dd, J = 8.1, 10.3 Hz, 1H), 5.32 (d, J = 3.2 Hz, 1H), 5.60 (s, 1H,

CHPh), 7.35-7.38 (m, 3H), 7.47-7.53 (m, 4H), 7.63 (apparent t, J = 7.2, 7.8 Hz, 1H), 8.06-8.08

(d, J = 7.8 Hz, 2H). The spectral data were consistent with those in the literature.7

O

OMeBzO

BzOBzO

HO

2

TCCA, TMSOTf

CH2Cl2

OBzO

BzOOBz

STol

OBz

4

OBzO

BzOOBz

OBz

26

O

OMeBzO

BzOBzO

O


S‐13

Methyl (2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)-(1→6)-2,3,4-tri-O-benzoyl-α-D





was added to it. Then TMSOTf (5.3 µL, 0.029 mmol) was added via a micro-syringe. The

reaction mixture was warmed to room temperature quickly. After the acceptor was consumed




anhydrous Na2SO4 and concentrated to afford the glycosylated product. The crude product was

purified by flash column chromatography on silica gel (230-400 mesh) using PE:EtOAc 5:1 to

afford 26 (99.8 mg) in 93% as white foam. 1H (300 MHz, CDCl3): δ 3.10 (s, 3H, OCH3), 3.80 (dd, 1H, J = 7.5, 11.0 Hz), 4.16-4.41 (m,

4H), 4.59 (m, 1H), 4.91-4.96 (m, 2H), 5.05 (dd, 1H, J = 3.0, 10.0 Hz), 5.29 (t, 1H, J = 12.0 Hz),

5.65 (dd, 1H, J = 3.0, 10.0 Hz), 5.85 (m, 1H), 6.00 (d, 1H, J = 3.3 Hz), 6.05 (t, 1H, J = 9.0 Hz),

7.26-7.49 (m, 21H, ArH), 7.77-8.01 (m, 14H, ArH). The spectral data were consistent with those

in the literature.8

Methyl (2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-α-D


To a mixture of glycosyl donor 4 (78.56 mg, 0.111 mmol) and 14 (43 mg, 0.093 mmol) in dry

CH2Cl2 (4 mL), flame activated 4Å molecular sieves were added. It was stirred at room

temperature under argon atmosphere. After 40 mins the mixture was cooled to -5ºC and TCCA

(21.5 mg, 0.093 mmol) was added to it. Then TMSOTf (5.0 µL, 0.028 mmol) was added via a

micro-syringe. After the acceptor was consumed completely (checked by TLC) the reaction was


S‐14

quenched by triethylamine (50.0 µL). Molecular sieves were filtered off through celite bed. The

filtrate was diluted with CH2Cl2 and washed subsequently with saturated NaHCO3 solution and

water. The organic layer was dried over anhydrous Na2SO4 and concentrated to afford the

glycosylated product. The crude product was purified by column chromatography (PE/EtOAc

5:1) on silica gel (60-120 mesh) to afford 27 (78.3 mg) in 81% as colorless syrup. 1H (300 MHz, CDCl3): δ 3.30 (s, 3H, OCH3), 3.41-3.54 (m, 3H), 3.69 (m, 1H), 3.88-3.98 (m,

2H), 4.02 (apparent t, J = 9.1, 9.6 Hz, 1H), 4.18 (dd, J = 7.7, 11.3 Hz, 1H), 4.31 (d, J = 12.2 Hz,

1H), 4.39 (dd, J = 5.8, 11.2 Hz, 1H), 4.57-4.65 (m, 2H), 4.73-4.81 (m, 3H), 4.90 (d, J = 11.2 Hz,

1H), 5.17 (d, J = 11.1 Hz, 1H), 5.29 (dd, J = 3.5, 10.4 Hz, 1H), 5.69 (m, 1H), 5.84 (m, 1H), 7.19-

7.58 (m, 27H, ArH), 7.74-7.77 (d, 2H, ArH), 7.83-7.86 (d, 2H, ArH), 7.92-7.95 (d, 2H, ArH),

8.00-8.03 (d, 2H, ArH). The spectral data were consistent with those in the literature.8

Methyl (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-(1→4)-2,3-di-O-benzoyl-6-O-benzyl-

α-D-glucopyranoside (30)




followed by TMSOTf (5.5 µL, 0.03 mmol) were added to it. The reaction mixture was warmed

gradually to room temperature. After the acceptor was consumed completely (checked by TLC)

the reaction was quenched by triethylamine (55.0 µL). Molecular sieves were filtered off through

celite bed. The filtrate was diluted with CH2Cl2 and washed subsequently with saturated

NaHCO3 (50 mL) solution and water (50 mL). The organic layer was dried over anhydrous

Na2SO4 and concentrated to afford the glycosylated product. The crude product was purified by

flash chromatography (PE:EtOAc 8:1) on silica gel (230-400 mesh) to give 30 (91.7 mg) in 89%

as colorless syrup.

[α]25D +61.9 (c 2.09, CHCl3).


S‐15

1H NMR (CDCl3, 300 MHz) δ: 3.41 (s, 3H, OCH3), 3.45-3.51 (m, 2H), 3.71 (d, J = 9.8 Hz, 1H),

3.78-3.89 (m, 3H), 3.99-4.03 (m, 4H), 4.28-4.42 (m, 4H), 4.48-4.55 (m, 2H), 4.59-4.65 (m, 3H),

4.84 (m, 1H), 5.11 (d, J = 2.4 Hz, 1H, 1-H'), 5.18 (d, J = 3.6 Hz, 1H, 1-H), 5.24 (m, 1H), 6.13

(apparent t, J = 9.3, 10.1 Hz, 1H), 7.12-7.51 (m, 31H, ArH), 7.96-8.00 (m, 4H, ArH). 13C NMR (75 MHz, CDCl3) δ: 55.3, 70.2, 70.4, 72.1, 72.3, 72.7, 73.2, 73.26, 73.34, 74.6, 74.9,

75.3, 75.8, 78.6, 96.8 (1-C), 98.8 (1-C'), 127.3, 127.37, 127.43, 127.5, 127.6, 127.7, 128.0,

128.1, 128.2, 128.3, 129.7, 129.9, 133.1, 138.0, 138.2, 138.4, 138.6, 138.9, 165.7 (C=O), 166.0

(C=O).

HRMS m/z calcd for (C62H62O13Na+) calcd: 1037.4088, found: 1037.4087.

Methyl (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-α-D-

glucopyranoside (32α)9 and Methyl (2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-(1→4)-

2,3,6-tri-O-benzyl-α-D-glucopyranoside (32β)9

A mixture of 31 (83.5 mg, 0.129 mmol), 14 (50 mg, 0.108 mmol) and flame activated 4Å

molecular sieves were stirred in dry solvent (4 mL) for 30 min at room temperature under argon

atmosphere. The mixture was cooled to -5ºC and TCCA (25.1 mg, 0.108 mmol) was added to it.

Then TMSOTf (5.9 µL, 0.032 mmol) was added via a micro-syringe. After the acceptor was

consumed completely (checked by TLC) the reaction was quenched by triethylamine (59.0 µL).

Molecular sieves were filtered off through celite bed. The filtrate was diluted with CH2Cl2 and

washed subsequently with saturated NaHCO3 solution and water. The organic layer was dried

over anhydrous Na2SO4 and concentrated to afford the glycosylated product. The crude residue

was directly purified by silica gel (230-400 mesh) flash column chromatography


S‐16

(CH2Cl2/hexane, 3:2) to afford the compounds (91.4 mg) in 86% (α/β 1.1:1) [32α as colorless

syrup and 32β as white foam].

32α : 1H NMR (CDCl3, 500 MHz): δ 3.30 (s, 3H, OCH3), 3.32 (s, 1H), 3.40 (d, J = 3.5 Hz, 1H),

3.42 (d, J = 3.5 Hz, 1H), 3.51 (dd, J = 3.5, 9.0 Hz, 1H), 3.54-3.58 (m, 2H), 3.63 (d, J = 10.0 Hz,

1H), 3.73-3.78 (m, 2H), 3.83 (t, J = 9.2 Hz, 1H), 3.96 (t, J = 9.0 Hz, 1H), 4.00 (t, J = 9.0 Hz,

1H), 4.20 (d, J = 12.5 Hz, 1H), 4.34 (d, J = 11.0 Hz, 1H), 4.41 (s, 3H), 4.43 (d, J = 12.0 Hz, 1H),

4.47 (d, J = 5.5 Hz, 1H), 4.50 (s, 1H), 4.52 (d, J = 3.5 Hz, 1H), 4.62 (d, J = 12.5 Hz, 1H), 4.70

(d, J = 5.0 Hz, 1H), 4.71 (d, J = 4.5 Hz, 1H), 4.72 (d, J = 11.0 Hz, 1H), 4.80 (d, J = 10.5 Hz, 1H),

4.95 (d, J = 11.5 Hz, 1H), 5.61 (d, J = 4.0 Hz, 1H), 7.02-7.23 (m, 35H, ArH).

32β : 1H NMR (CDCl3, 500 MHz): 3.21 (m, 1H), 3.29 (s, 3H, OCH3), 3.30 (m, 1H), 3.37-3.41

(m, 3H), 3.47 (dd, J = 4.5, 11.0 Hz, 1H), 3.50-3.54 (m, 2H), 4.63 (dd, J = 1.8, 10.8 Hz, 1H), 3.75

(dd, J = 3.5, 10.0 Hz, 1H), 3.77 (t, J = 9.5 Hz, 1H), 3.88 (t, J = 9.5 Hz, 1H), 4.28-4.32 (m, 3H),

4.36 (d, J = 12.5 Hz, 1H), 4.46-4.48 (m, 2H), 4.49 (d, J = 5.5 Hz, 1H), 4.52 (d, J = 12.0 Hz, 1H),

4.53 (s, 1H), 4.65-4.68 (m, 3H), 4.70-4.71 (m, 2H), 4.73 (d, J = 3.5 Hz, 1H), 4.79 (d, J = 11.0

Hz, 1H), 5.01 (d, J = 11.0 Hz, 1H), 7.01-7.34 (m, 35H, ArH). The spectral data were consistent

with those in the literature.9

Methyl (2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-α-D-


A mixture of 33 (81.5 mg, 0.129 mmol), 14 (50 mg, 0.108 mmol) and flame activated 4Å

molecular sieves were stirred in dry solvent (4 mL) for 30 min at room temperature under argon

atmosphere. Then the mixture was cooled to -5ºC and TCCA (25.1 mg, 0.108 mmol) was added

to it. Then TMSOTf (5.9 µL, 0.032 mmol) was added via a micro-syringe. After the acceptor

was consumed completely (checked by TLC) the reaction was quenched by triethylamine (59.0

µL). Molecular sieves were filtered off through celite bed. The filtrate was diluted with CH2Cl2

and washed subsequently with saturated NaHCO3 solution and water. The organic layer was


S‐17

dried over anhydrous Na2SO4 and concentrated to afford the glycosylated product. The crude

residue was directly purified by silica gel (230-400 mesh) flash column chromatography

(PE:EtOAc 4:1) to afford 34 (87.1 mg) in 82% as colorless syrup. 1H NMR (CDCl3, 500 MHz): δ 3.32 (bs, 3H, OCH3), 3.45-3.50 (m, 2H), 3.58 (dd, J = 5.0, 11.0

Hz, 1H), 3.64-3.65 (m, 5H), 3.72-3.75 (m, 2H), 4.79 (dd, J = 2.8, 9.2 Hz, 1H), 3.89 (t, J = 9.5

Hz, 1H), 4.13 (d, J = 12.0 Hz, 1H), 4.23 (d, J = 12.0 Hz, 1H), 4.35 (dd, J = 2.5, 12.0 Hz), 4.42

(apparent t, J = 9.0, 11.0 Hz, 1H), 4.47 (s, 1H), 4.49-4.54 (m, 6H), 4.62 (d, J = 12.0 Hz, 1H),

4.76 (d, J = 10.5 Hz, 1H), 5.01 (d, J = 11.5 Hz, 1H), 5.21 (d, J = 2.0 Hz, 1H), 7.11-7.23 (m, 35H,

ArH). The spectral data were consistent with those in the literature.10

Methyl (2,3,4-tri-O-acetyl-α-L-rhamanopyranosyl)-(1→4)-(2,3,4-tri-O-acetyl-α-L-

rhamanopyranosyl)-(1→6)-2,3-di-O-benzyl-α-D-glucopyranoside (36)7



atmosphere. After 40 min the mixture was cooled to -5ºC and TCCA (41.9 mg, 0.18 mmol) was

added to it. Then TMSOTf (8.9 µL, 0.049 mmol) was added via a micro-syringe. After 5 min,

the reaction was removed from ice-bath and stirred at room temperature for 45 minutes. After the


triethylamine (89.0 µL). Molecular sieves were filtered off through celite bed. The filtrate was

diluted with CH2Cl2 and washed subsequently with saturated NaHCO3 (50 mL) solution and

water (50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to afford

the the glycosylated product. The crude product was purified by flash column chromatography

on silica gel (230-400 mesh) using PE/EtOAc 2:1 to afford 36 (60.6 mg) in 81% as white foam. 1H (300 MHz, CDCl3): δ 0.79 (d, J = 6.2 Hz, 3H), 1.20 (d, J = 6.2 Hz, 3H), 1.97 (s, 3H,

COCH3), 1.98 (s, 3H, COCH3), 1.99 (s, 3H, COCH3), 2.04 (s, 3H, COCH3), 2.09 (s, 3H,


S‐18

COCH3), 2.12 (s, 3H, COCH3), 3.39 (s, 3H, OCH3), 3.60 (dd, J = 3.6, 9.4 Hz, 1H), 3.65-3.78 (m,

3H), 3.83-3.95 (m, 3H), 4.00 (m, 1H), 4.57-4.64 (m, 2H), 4.72 (d, J = 5.1 Hz, 1H), 4.76 (d, J =

6.2 Hz, 1H), 4.80 (d, J = 1.5 Hz, 1H), 4.88 (d, J = 1.5 Hz, 1H), 4.99 (m, 1H), 5.03-5.10 (m, 3H),

5.13 (dd, J = 1.7, 3.5 Hz, 1H), 5.23 (dd, J = 3.4, 10.3 Hz, 1H), 5.27 (dd, J = 3.6, 10.1 Hz, 1H),

7.25-7.39 (m, 10H, ArH). The spectral data were consistent with those in the literature.7

References

1. S. Hanessian, O. M. Saavedra, V. Mascitti, W. Marterer, R. Oehrlein, C-P. Mak,

Tetrahedron. 2001, 57, 3267.

2. C. Lucas-Lopez; N. Murphy; X. Zhu, Eur. J. Org. Chem, 2008, 4401.

3. B. Mukhopadhyay; S. V. Maurer; N. Rudolph; R. M. van Well; D. A. Russell; R. A.

Field, J. Org. Chem. 2005, 70, 9059.

4. Z. Szurmai; A. Lipták; G. Snatzke, Carbohydrate Research, 1990, 200, 201.

5. J. Srivastava, A. Khare, N. K. Khare, Ind. J. Chem, 2009, 48B, 848.

6. T. Nokami; Y. Nozaki; Y. Saigusa; A. Shibuya; S. Manabe; Y. Ito; J-i. Yoshida, Org.

Lett. 2011, 13, 1544.

7. S. Deng; U. Gangadharmath, C-W Tom Chang, J. Org. Chem. 2006, 71, 5179.

8. Peng, P.; Ye, X.-S. Org. Biomol. Chem. 2011, 9, 616.

9. a) J. Tatai, P. Fügedi, Org. lett. 2007, 9, 4647; b) B. A. Garcia, D. Y. Gin, J. Am. Chem.

Soc. 2000, 122, 4269; c) S. K. Maity, N. Basu, Carbohydr. Res. 2012, 354, 40.

10. K.-T. Huang, N. Winssinger, Eur. J. Org. Chem, 2007, 1887.


S‐19

O

O

OB

z

O BzOO

Ph

3

O

OM

eB

zO

BzO B

zO


S‐20

OO

OB

z

O BzOO

Ph

3

O

OM

eB

zO

BzO B

zO


S‐21

O

O

OB

z

O BzOO

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3

O

OM

eB

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BzO B

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S‐22

O

O

OB

z

O BzOO

Ph

3

O

OM

eB

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BzO B

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S‐23

O

OB

z

BzO

OB

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OB

z

ON

HC

bz

6


S‐24

O

OB

z

BzO

OB

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OB

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ON

HC

bz

6


S‐25

O

OM

e

OB

z

BzO B

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AcO A

cOP

hthN

AcO

12


S‐26

O

OM

e

OB

z

BzO B

zOOO

AcO A

cOP

hthN

AcO

12


S‐27

O

OM

e

OB

z

BzO B

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AcO A

cOP

hthN

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12


S‐28

O

OM

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OB

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cOP

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12


S‐29

30

O

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n

Bn

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Bn

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eB

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Bn

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S‐30

30

O

OB

n

Bn

O

Bn

O

OB

n OO

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Bn

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S‐31

30

O

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Bn

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OB

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S‐32

30

O

OB

n

Bn

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Bn

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OB

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Bn

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Nabamita Basu, Sajal Kumar Maity, Rina Ghosh* - rsc.org · Nabamita Basu, Sajal Kumar Maity, Rina Ghosh* Department of Chemistry, Jadavpur University, Kolkata 700 032, India. Fax:

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