Eur. J. Org. Chem. 2007 · © WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2007 · ISSN 1434–193X

SUPPORTING INFORMATION

Title: Direct Preparation of N-Glycosidic Bond-Linked Nonionic Carbohydrate-Based Surfactant (NICBS) via Ritter Reaction Author(s): Zerong Daniel Wang,* Samia O. Sheikh, Shannon Cox, Yulu Zhang, Keegan Massey Ref. No.: O200700079

1. General The high-speed shaker used in this study was a Wrist ActionTM

Shaker (Model 75) purchased from Burrell Scientific (Pittsburg, PA, USA). High resolution mass spectra (HRMS) were recorded in MALDI mode on a Voyager-DE STR 4160, using α-cyano-4-hydroxycinnamic acid as matrix, at the Department of Chemistry, University of Houston. 1H- and 13C-NMR were recorded in CDCl3 with a Bruker Avance 600 MHz NMR spectrometer (at 600 Mz for 1H and 150 MHz for 13C, respectively, TMS as internal standard) at the Keck/IMD NMR center founded by the W. M. Keck Foundation and the University of Houston. The unacylated surfactant molecules were purified on silica gel using EtOAc/MeOH (5:1 to 3:1) as eluent, whereas the acetylated products were purified by silica gel column chromatography using hexane/EtOAc (5:1 to 3:2) as eluent. Thin-layer chromatography (TLC) was performed on silica gel (precoated silica gel plate F254, Merck) and detected by heating with 1.5% H2SO4 in EtOH.

2. Direct preparation of 1-N-lauroyl-2,3,4,6-tetraacetyl-β-D-glucopyranosylamine from β-D-glucose pentaacetate

To an 18 mL of scintillation vial were added 0.2169 g of β-D-glucose pentaacetate (0.56 mmol), 1.0 mL of undecyl cyanide (d = 0.827 g/mL, 4.56 mmol), 0.1048 g of AgClO4 (0.5 mmol), and 0.5 mL of TMSOTf (d = 1.228 g/mL, 2.76 mmol). The vial was capped and mounted to the high-speed shaker. After 24 hours, the reaction was quenched by 0.5 mL of Et3N and 0.1663 g of 1-N-lauroyl-2,3,4,6-tetraacetyl-β-D-glucopyranosylamine was isolated by column chromatography, in yield of 56%.

3. The reaction between glucose and 4-methylbenzyl cyanide To an 18 mL of scintillation vial were added 0.2418 g of D-glucose (1.34 mmol), 1.5 mL of 4-methylbenzyl cyanide (d = 0.992 g/mL, 11.3 mmol), 0.1244 g of AgClO4 (0.6 mmol), and 0.5 mL of TMSOTf (2.76 mmol). The vial was capped and mounted to the high-speed shaker. After 24 hours, the reaction was quenched by 0.5 mL of Et3N and the mixture was directly loaded to a 10 cm silica gel column and washed with hexane/EtOAc (2:1 to 1:1) to remove unreacted cyanide and Et3N, and 0.1218 g of colorless oil was obtained, when the column was eluted with EtOAc/MeOH (5:1) (Rf = 0.80 for EtOAc/MeOH = 3:1), which was further acetylated with Ac2O in pyridine. The reaction mixture was diluted with 50 mL of EtOAc, and washed with 1N HCl (3 × 20 mL), saturated NaHCO3 aqueous solution (2 × 20 mL) and brine (20 mL), and dried over CaCl2. After removal of solvent, the residue was purified by silica gel column chromatography using hexane/EtOAc (3:1) to afford 75 % of 1-N,6-di(4-methylphenyl)-acetyl-2,3,4-triacetyl-β-D-glucopyranosylamine, as evidenced from the following NMR characterization, as well as high resolution Mass spectroscopy. 4. The reaction between glucose and cyclopropyl cyanide

To an 18 mL of scintillation vial were added 0.225 g of D-glucose (1.25 mmol), 1.5 mL of cyclopropyl cyanide (d = 0.911 g/mL, 20.4 mmol), 0.135 g of AgClO4 (0.65 mmol), and 0.5 mL of TMSOTf (2.76 mmol). The vial was capped and mounted to the high-speed shaker. After shaking for 3 hours, most of the solid sugar disappeared, and after 24 hours, the reaction was quenched by 0.5 mL of Et3N and the mixture was directly loaded to a 10 cm silica gel column and washed with hexane/EtOAc (2:1 to 1:1) to remove unreacted cyanide and Et3N, and 0.223 g of very viscous oil (68.8%) was obtained when

the column was further eluted with EtOAc/MeOH (5:1) (Rf = 0.41 for EtOAc/MeOH = 3:1), which was then acetylated with Ac2O in pyridine. The reaction mixture was diluted with 50 mL of EtOAc, and washed with 1N HCl (3 × 20 mL), saturated NaHCO3 aqueous solution (2 × 20 mL) and brine (20 mL), and dried over CaCl2. After removal of solvent, the residue was purified by silica gel column chromatography using hexane/EtOAc (3:1) to afford 0.1671 g of 1-N-(cyclopropyl)formyl-2,3,4,6-tetracetyl-β-D-glucopyrano-sylamine (47.7%), as evidenced from the following NMR characterization, as well as high resolution Mass spectroscopy. 5. Summary of high resolution MS of prepared surfactant molecules from D-glucose

Nitrile Structure Formula Calc. MS

Found MS

CH3CN

O HN CH3

O

OAc

AcOAcO

OAc

C16H23NO10Na 412.1220 412.1219

n-C11H23CN

O HN

O

OAc

AcOAcO

OAc8

C26H43NO10Na 552.2785 552.2790

4-CH3C6H4CH2CN

O HN

O

O

AcOAcO

OAc

O

[a]

C30H35NO10Na 592.2159 592.2152

c-C3H5-CN

O HN

O

OAc

AcOAcO

OAc

C18H25NO10Na 438.1376 438.1355

[a] the second (4-methylphenyl)acetyl group is assigned to position 6, for the nucleophilic attack of OH on cyano group to form ester, because among the rest OHs, the 6-OH is primary OH, and has less steric hindrance than 2-OH, 3-OH and 4-OH.

0.15. 1

0.25.2

0. 35.3

0 .45.4

0.55.5

0 .65.6

0.75 .7

mpp0.85480.86670.8775

1.23871.25551.28071.29251.56081.57012.00942.02112.03102.06852.08452.11522.12772.14002.15282.16652.17442.17902.1915

3.80293.80453.80593.81964.05434.07484.29234.29934.31314.3201

4.88954.90554.92145.03505.05135.06745.23455.25025.26595.28185.29775.3134

6.18926.2047

7.2588

3.000

16.301

2.1903.0693.1963.5833.2471.2611.196

1.067

1.150

1.060

0.9380.9951.0201.005

1.055

CH

Cl3

NH

3-H

1-H 4-

H2-

H6-

H6‘

-H5-

HC

H2

CH

2

Ac’

s

CH

3

OH N

O

OAc

AcO AcO

OAc

8

NC

H2

O

mp p

0.45.4

0.55.5

0. 65.6

mpp

5. 3

0. 4

5. 4

0. 5

5.5

0. 6

m pp

6.38.3

0.42.4

4.46.4

8.40.5

2.54. 5

6.58.5

0.62.6

4.6mpp

0 6 26 46 66 86 07 27 47 67 87 08

NH

NH

OH N

O

OAc

AcO AcO

OAc

8

0203

0405

060 7

0 80 9

0010 11

0 210 31

04 105 1

061071

081mpp

14.074620.552220.613920.696822.637625.120429.070529.256229.406929.551831.857236.6482

61.610168.128769.783670.574172.642873.508276.785976.997777.209277.465278.1058

169.5523169.8294170.5914171.0123173.3881

OH N

O

OAc

AcO AcO

OAc

8

5.1

0.2

5.2

0.3

5.3

0.4

5.4

0.5

5.5

0.6

5.6

0.7

5.7

0.8

mp

p

2.00232.0228

2.0387

2.0597

2.0830

3.84083.84463.84813.85423.85773.86153.86504.07914.08244.09994.10324.29694.30444.31774.32524.91404.92994.94595.04615.06255.07875.26145.27715.29295.29625.31215.3280

6.61156.6271

2.7592.7223.5623.1223.426

1.0001.0211.059

0.9610.9870.9281.053

0.985

OH N

CH3

O

OAc

AcO AcO

OAc

NH

3-H

1-H

4-H2-

H

6-H

6-H

5-H

Ac’

s

030 4

0 50 6

0 708

0900 1

01 102 1

0 310 41

051061

071081

mpp

20.405420.485320.547723.1348

61.5785

68.012770.457372.673973.351276.789177.001277.212277.9573

169.4428169.7069170.4174170.4679170.7168

OH N

CH3

O

OAc

AcO AcO

OAc

1-C5-

C3-C

2-C4-

C

6-C

Ac’

s

CO

’s

mpp

0.45.4

0.55.5

0.65.6

mpp

0.4

5.4

0.5

5.5

0.6

5.6

mpp

0.45.4

0.55 .5

0.65.6

mpp

26 46 66 86 07 27 47 67 87

H-H

CO

SYH

-C H

SQC

OH N

CH3

O

OAc

AcO AcO

OAc

NH

NH

0.15.1

0.25. 2

0. 35 .3

0.45.4

0. 55.5

0 .65.6

0.75.7

mpp

1.7929

1.84131.9054

2.24002.2435

3.45993.5220

3.78383.79844.01204.03064.0322

4.16444.17154.1852

4.1921

4.88744.90334.91964.99985.00905.01685.0256

5.21155.22755.24365.73955.74995.7609

6.44846.4605

6.98056.99147.00767.02127.03757.05197.06307.07647.09017.0997

2.3852.6342.633

6.413

1.7612.073

0.773

0.8341.000

0.8160.971

0.797

0.813

0.850

8.995

CH

Cl3

NH

1-H

3-H

2-H

4-H

6-H

6‘-H

5-H

CH

3

Ac A

c Ac

OH N

O

O

AcO AcO

OAcO

0304

0506

0708

09001

011021

031041

051061

071m

pp

20.398720.504921.003323.0124

29.6540

40.401340.7431

62.005068.007368.274468.5010

69.963974.096576.786276.997577.2089

128.8781129.2344129.4407130.4903136.6842137.0810

169.3076169.6424170.4652170.6819171.5306

1-C

2-C

4-C

5-C

3-C

6-C

Ac

CH

2

CH

3

CH

3

OH N

O

O

AcO AcO

OAcO

mpp

8.30.4

2.44.4

6.48.4

0.52.5

4.56.5

8.50.6

2.64.6

6. 6mpp

0.4

5.4

0.5

5.5

0.6

5. 6

mpp

8.30.4

2.44.4

6.48.4

0.52.5

4 .56 .5

8. 50.6

2.64.6

mpp

26 46 66 86 07 27 47 67 87 08

H-H

CO

SYH

-C H

SQC

OH N

O

O

AcO AcO

OAcO

NH

NH

0. 15.1

0.25.2

0.35. 3

0.45 .4

0.55.5

0.65.6

0.75.7

mpp

0.76350.77500.81170.92850.93530.97281.18151.19341.2053

1.4687

1.96841.98031.98592.0122

3.91353.99144.01224.04164.05374.06554.07744.23164.23854.25224.2591

4.99585.01185.02805.10205.10915.11745.34755.3622

5.8185

6.98886.9991

2.106

2.285

0.995

1.020

9.4644.212

0.9101.1910.7581.148

1.0531.207

0.926

0.961

0.885

CH

Cl3

EtO

Ac

EtO

Acc-

pro

pyl

c-p

rop

ylN

H1-

H3-

H2-

H4-

H6-

H6‘

-H5-

H

Ac

Ac

OH N

O

OAc

AcO AcO

OAc

0203

0405

0607

0 80 9

001011

021031

04105 1

0610 71

mpp

7.98168.1402

14.4661

20.468420.604420.9583

61.7060

67.867068.300068.424970.156974.161876.789677.000577.2134

169.0787169.3349170.3496170.7089174.4513

1-C3-

C2-C

4-C

6-C

5-C

c-p

rop

yl

c-p

rop

yl

Ac

OH N

O

OAc

AcO AcO

OAc

mpp

0. 45.4

0 .55. 5

0.65.6

0.7mpp

0.4

5.4

0.5

5.5

0.6

5.6

0.7

mpp

0.45.4

0.55.5

0.65.6

0.7mpp

26 46 66 86 07 27 47 67

H-H

CO

SYH

-C H

SQC

OH N

O

OAc

AcO AcO

OAc