First Detection of Unprotected 1,2-Anhydro Aldopyranoses

Transcription

1 First Detection of Unprotected 1,2-Anhydro Aldopyranoses Kazunari Serizawa, Masato Noguchi, Gefei Li, and Shin-ichiro Shoda* Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, , Aoba, Sendai, Miyagi (Received April 7, 2017; CL ; Copyright The Chemical Society of Japan

2 Supporting information for First Detection of Unprotected 1,2-Anhydro Aldopyranoses Kazunari Serizawa, Masato Noguchi, Gefei Li and Shin-ichiro Shoda* Graduate School of Engineering, Tohoku University, Aoba, Sendai List of contents General Procedure 2 Evaluation of the stability of unprotected 1,2-anhydroglucose in D 2 / CH 3 CN (1/1 (v/v)) 2 Synthesis of 1,2-anhydro-α-D-glucopyranose 3 Characterization of 6-dimethylimidazoliniumoxy-1,2-anhydro glucose 3 Synthesis of 1,2-anhydro-α-D-glucopyranose (Dehydrating agent: CDMBI) 3 Synthesis of 1,2-anhydro-β-D-mannopyranose 3 Synthesis of 1,2-anhydro-α-D-allopyranose 3 Synthesis of 1,2-anhydro-α-D-galactopyranose 4 Synthesis of 1,2-anhydro-β-L-rhamnopyranose 4 Synthesis of 1,2-anhydro-α-D-xylopyranose 4 Synthesis of 1,2-anhydro cellobiose 4 Synthesis of 1,2-anhydro lactose 5 Synthesis of 1,2-anhydro xylobiose 5 Synthesis of 1,2-anhydro maltose 5 Synthesis of 1,2-anhydro melibiose 6 Synthesis of 1,2-anhydro isomaltotriose 6 NMR spectra of 1,2-anhydro-α-D-glucopyranose 7 NMR spectra of 1,2-anhydro-α-D-glucopyranose (Dehydrating agent: CDMBI) 11 NMR spectra of 1,2-anhydro-β-D-mannopyranose 15 NMR spectra of 1,2-anhydro-α-D-allopyranose 19 NMR spectra of 1,2-anhydro-α-D-galactopyranose 23 NMR spectra of 1,2-anhydro-β-L-rhamnopyranose 27 NMR spectra of 1,2-anhydro-α-D-xylopyranose 31 NMR spectra of 1,2-anhydro cellobiose 35 NMR spectra of 1,2-anhydro lactose 39 NMR spectra of 1,2-anhydro xylobiose 43 NMR spectra of 1,2-anhydro maltose 47 NMR spectra of 1,2-anhydro melibiose 51 NMR spectra of 1,2-anhydro isomaltotriose 55 DMC: 2-chlorodimethylimidazolinium chloride CDMBI: 2-chlorodimethylbenzimidazolium chloride 1

3 General procedure; A base was added to a mixture of unprotected sugar and dehydrating agent in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) in ice/nacl bath. NMR spectra were recorded on Bruker AVANCE III 400 at -10 ºC in D 2 /CH 3 CN = 1/1. Chemical shifts ( ) are reported in parts per million relative to CH 3 CN ( 1 H NMR 2.06 ppm, 13 C NMR ppm). Assignments of 1 H and 13 C NMR spectra were performed by H-H CSY, HSQC and HSQC-TCSY experiments. The J CH coupling constant values were determined from 13 C NMR spectrum without composite pulse decoupling. Evaluation of the stability of unprotected 1,2-anhydro glucose in D 2 /CH 3 CN (1/1 (v/v)); Triethylamine (0.105 ml, mmol) was added to a mixture of D-glucose (22.5 mg, mmol) and DMC (42.3 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After confirming the complete consumption of DMC, the hydrolysis of 1,2-anhydro glucose to glucose was monitored by 1 H NMR at -10 o C. The content of remained 1,2-anhydro glucose was determined by comparing the integral of the anomeric proton of 1,2-anhydro glucose and that of the satellite peak of acetonitrile. time (min) The percentage of remained 1,2-anhydro glucose standardized by its initial content (%)

4 Synthesis of 1,2-anhydro-α-D-glucopyranose Triethylamine (0.105 ml, mmol) was added to a mixture of D-glucose (22.5 mg, mmol) and DMC (42.3 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.05 (1H, d, H-1, J = 2.0 Hz), 3.84 (1H, d, H-3, J = 8.3 Hz), 3.72 (2H, d, H-6, J = 3.0 Hz), (1H, m, H-5), 3.36 (1H, dd, H-4, J = 8.3, 10.3 Hz), 3.06 (1H, d, H-2, J = 2.4 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 78.7 (1C, C-1, J CH = 213 Hz), 72.1 (1C, C-5), 71.4 (1C, C-3), 68.6 (1C, C-4), 61.1 (1C, C-6), 56.5 (1C, C-2, J CH = 181 Hz). Characterization of 6-dimethylimidazoliniumoxy-1,2-anhydro glucose 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.12 (1H, d, H-1, J = 2.0 Hz), 4.79 (1H, H-6 a ), 4.66 (1H, H-6 b ) 3.91 (1H, d, H-3, J = 8.5 Hz), 3.81 (4H, -CH 2 - of imidazoline ring), 3.79 (1H, H-5), 3.49 (1H, H-4), 3.11 (1H, d, H-2, J = 2.0 Hz), 3.04 (6H, -CH 3 of imidazoline ring). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); (1C, 2 position of imidazolinium moiety) 78.7 (1C, C-1, J CH = 213 Hz), 75.5 (1C, C-6), 71.2 (1C, C-3), 70.3 (1C, C-5), 68.1 (1C, C-4), 56.4 (1C, C-2, J CH = 183 Hz), 48.5 (1C, -CH 2 - of imidazoline ring), 33.8 (1C, -CH 3 of imidazoline ring) Synthesis of 1,2-anhydro-α-D-glucopyranose (Dehydrating agent: CDMBI) Triethylamine (0.157 ml, 1.13 mmol) was added to a mixture of D-glucose (22.5 mg, mmol) and CDMBI (81.4 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. Synthesis of 1,2-anhydro-β-D-mannopyranose Triethylamine (0.157 ml, 1.13 mmol) was added to a mixture of D-mannose (22.5 mg, mmol) and CDMBI (81.4 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.02 (1H, d, H-1, J = 2.8 Hz), 4.02 (1H, H-3), (2H, H-6), 3.62 (1H, H-4), 3.60 (1H, H-5), 3.41 (1H, t, H-2, J = 2.5 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 80.6 (1C, C-5), 80.3 (1C, C-1, J CH = 216 Hz), 72.2 (1C, C-3), 69.8 (1C, C-4), 61.7 (1C, C-6), 58.6 (1C, C-2, J CH = 182 Hz). Synthesis of 1,2-anhydro-α-D-allopyranose Triethylamine (0.157 ml, 1.13 mmol) was added to a mixture of D-allose (22.5 mg, mmol) and CDMBI (81.4 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) 3

5 around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.06 (1H, d, H-1, J = 2.5 Hz), 4.29 (1H, H-3), 3.80 (1H, H-5), 3.69 (2H, s, H-6), 3.64 (1H, H-4), 3.34 (1H, H-2). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 78.9 (1C, C-1, J CH = 214 Hz), 72.6 (1C, C-5), 66.6 (1C, C-4), 64.5 (1C, C-3), 61.7 (1C, C-6), 54.7 (1C, C-2, J CH = 186 Hz). Synthesis of 1,2-anhydro-α-D-galactopyranose Triethylamine (0.105 ml, mmol) was added to a mixture of D-galactose (22.5 mg, mmol) and DMC (42.3 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.05 (1H, d, H-1, J = 2.5 Hz), 3.91 (1H, H-3), 3.72 (1H, d, H-4, J = 3.5 Hz), 3.66 (2H, H-6), 3.58 (1H, dd, H-5, J = 5.5, 7.3 Hz), 2.98 (1H, dd, H-2, J = 1.8, 2.5 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 78.5 (1C, C-1, J CH = 214 Hz), 71.6 (1C, C-5), 67.8 (1C, C-3), 63.7 (1C, C-4), 62.0 (1C, C-6), 54.1 (1C, C-2, J CH = 182 Hz) Synthesis of 1,2-anhydro-β-L-rhamnopyranose Triethylamine (0.157 ml, 1.13 mmol) was added to a mixture of L-rhamnose (20.5 mg, mmol) and CDMBI (81.4 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 4.94 (1H, d, H-1, J = 2.8 Hz), 3.94 (1H, dd, H-3, J = 2.3, 8.5 Hz), 3.65 (1H, dd, H-5, J = 6.2, 10.2 Hz), 3.40 (1H, d, H-2, J = 2.8 Hz), 3.34 (1H, dd, H-4, J = 8.5, 10.0 Hz), 1.19 (3H, d, CHCH 3, J = 6.3 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 80.2 (1C, C-1, J CH = 215 Hz), 76.8 (1C, C-5), 74.7 (1C, C-4), 72.1 (1C, C-3), 58.7 (1C, C-2, J CH = 181 Hz), 18.4(1C, C-6). Synthesis of 1,2-anhydro-α-D-xylopyranose Triethylamine (0.157 ml, 1.13 mmol) was added to a mixture of D-xylose (18.8 mg, mmol) and CDMBI (81.4 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 4.98 (1H, d, H-1, J = 2.0 Hz), 3.86 (1H, d, H-3, J = 7.6 Hz), (1H, m, H-5 a ), 3.50(1H, m, H-4), 3.36(1H, m, H-5 b ), 3.04 (1H, d, H-2, J = 2.3 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 78.7 (1C, C-1, J CH = 214 Hz), 70.7 (1C, C-3), 68.9 (1C, C-4), 62.0 (1C, C-5), 56.4 (1C, C-2, J CH = 181 Hz). Synthesis of 1,2-anhydro-cellobiose 4

6 Triethylamine (0.078 ml, mmol) was added to a mixture of D-cellobiose (21.4 mg, mmol) and CDMBI (40.7 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.09 (1H, d, H-1, J = 2.0 Hz), 4.49 (1H, d, H-1, J = 8.0 Hz), 4.00(1H, H-3), 3.92 (1H, H-6 a ), (2H, m, H-6), (2H, m, H-6 b, H-5), 3.55 (1H, m, H-4), 3.46 (2H, m, H-5, H-3 ), 3.33 (1H, H-4 ), 3.25 (1H, dd, H-2, J = 8.3, 9.0 Hz), 3.10 (1H, d, H-2, J = 2.5 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); (1C, C-1 ), 78.6 (1C, C-1, J CH = 215 Hz), 78.3 (1C, C-4), 77.3 (1C, C-3 ), 76.8 (1C, C-5 ), 74.4 (1C, C-2 ), 71.1 (1C, C-4 ), 70.6 (1C, C-5), 70.4 (1C, C-3), 62.1 (1C, C-6 ), 60.4 (1C, C-6), 55.5 (1C, C-2, J CH = 182 Hz) Synthesis of 1,2-anhydro-lactose Triethylamine (0.078 ml, mmol) was added to a mixture of D-lactose (21.4 mg, mmol) and CDMBI (40.7 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.09 (1H, d, H-1, J = 2.0 Hz), 4.44 (1H, d, H-1, J = 7.8 Hz), 4.03 (1H, H-3), 3.87 (1H, H-4 ), (2H, m, H-6), 3.73 (2H, m, H-6 ), 3.70 (1H, m, H-5 ), 3.62 (1H, H-3 ), 3.60 (1H, H-5), 3.58 (1H, H-4), 3.50 (1H, H-2 ), 3.11 (1H, d, H-2, J = 2.5 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); (1C, C-1 ), 78.6 (1C, C-1, J CH = 215 Hz), 77.7 (1C, C-4), 76.6 (1C, C-5 ), 73.8 (1C, C-3 ), 72.1 (1C, C-2 ), 70.8 (1C, C-5), 70.5 (1C, C-3), 69.7 (1C, C-4 ), 62.3 (1C, C-6 ), 60.5 (1C, C-6), 55.6 (1C, C-2, J CH = 182 Hz). Synthesis of 1,2-anhydro-xylobiose Triethylamine (0.078 ml, mmol) was added to a mixture of D-xylobiose (17.6 mg, mmol) and CDMBI (40.7 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.02(1H, s, H-1), 4.40 (1H, d, H-1, J = 7.8 Hz), 4.00 (1H, H-3), 3.92 (1H, H-5 a ), 3.73 (1H, m, H-5 a ), 3.65 (1H, H-4), 3.56 (1H, m, H-4 ), 3.47 (1H, m, H-5 b ), 3.38 (1H, H-3 ), 3.28 (1H, H-5 b ), 3.19 (1H, t, H-2, J = 8.4 Hz), 3.08 (1H, d, H-2, J = 2.0 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 103.0(1C, C-1 ), 78.5 (1C, C-1, J CH = 214 Hz), 76.8 (1C, C-3 ), 76.3(1C, C-4), 74.0 (1C, C-2 ), 70.4 (1C, C-4 ), 68.8 (1C, C-3), 66.6 (1C, C-5 ), 59.5 (1C, C-5), 55.9 (1C, C-2, J CH = 183 Hz). Synthesis of 1,2-anhydro-maltose 5

7 N,N-Dimethylbutylamine (0.079 ml, mmol) was added to a mixture of D-maltose (21.4 mg, mmol) and DMC (31.7 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding N-butyldimethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.42 (1H, d, H-1, J = 3.5 Hz), 5.10 (1H, d, H-1, J = 1.8 Hz), 4.17 (1H, t, H-3, J = 3.6 Hz), (3H, H-6 a, H-6), (5H, m, H-6 b, H-4, H-5, H-5, H-3 ), 3.47 (1H, H-2 ), 3.32 (1H, H-4 ), 3.06 (1H, d, H-2, J = 2.3 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 99.0 (1C, C-1 ), 78.7 (1C, C-1, J CH = 215 Hz), 74.1 (1C, C-3 ), 73.9 (1C, C-5 ), 73.4 (1C, C-4), 72.8 (1C, C-2 ), 71.4 (1C, C-3), 70.6 (1C, C-4 ), 70.5 (1C, C-5), 61.9 (1C, C-6 ), 61.0 (1C, C-6), 56.3 (1C, C-2, J CH = 183 Hz) Synthesis of 1,2-anhydro-melibiose Triethylamine (0.078 ml, mmol) was added to a mixture of D-melibiose (21.4 mg, mmol) and CDMBI (40.7 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at 0 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.07 (1H, d, H-1, J = 1.8 Hz), 4.94 (1H, d, H-1, J = 3.5 Hz), (3H, m, H-6 a, H-4, H-5 ), 3.90 (1H, H-3), 3.84 (1H, H-3 ), 3.77 (1H, H-2 ), (4H, m, H-6, H-5, H-6 b ), 3.51 (1H, dd, H-4, J = 8.4, 10.2 Hz), 3.11 (1H, d, H-2, J = 2.3 Hz). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 99.6 (1C, C-1 ), 78.7 (1C, C-1, J CH = 214 Hz), 72.0 (1C, C-5 ), 71.6 (1C, C-3), 71.0 (1C, C-5), 70.7 (1C, C-3 ), 70.3 (1C, C-4 ), 69.7 (1C, C-2 ), 68.7 (1C, C-4), 66.3 (1C, C-6), 62.2 (1C, C-6 ), 56.5 (1C, C-2, J CH = 180 Hz). Synthesis of 1,2-anhydro-isomaltotriose Triethylamine (0.078 ml, mmol) was added to a mixture of D-isomaltotriose (31.5 mg, mmol) and CDMBI (40.7 mg, mmol) in D 2 /CH 3 CN (1/1 (v/v), 0.5 ml) around -20 ºC. After adding triethylamine, NMR spectra were recorded at -10 ºC. 1 H NMR (400 MHz, D 2 /CH 3 CN = 1/1); 5.09 (1H, s, H-1), 4.94 (1H, d, H-1, J = 3.0 Hz), 4.90 (1H, d, H-1, J = 3.0 Hz), (4H, m, H-6 a, H-6 a, H-5, H-3), (8H, m, H-6, H-5, H-3, H-3, H-5, H-6 b, H-6 b ), (4H, m, H-4, H-4, H-2, H-2 ), 3.38 (1H, t, H-4, J = 9.6 Hz), 3.11 (1H, s, H-2). 13 C NMR (101 MHz, D 2 /CH 3 CN = 1/1); 99.4 (1C, C-1 ), 98.9 (1C, C-1 ), 78.8 (1C, C-1, J CH = 213 Hz), 74.6 (1C, C-3 ), 74.3 (1C, C-3 ), 73.0 (1C, C-5 ), 72.9 (1C, C-2 ), 72.7 (1C, C-2 ), 71.8 (1C, C-3), 71.4 (1C, C-5 ), 70.8 (2C, C-5, C-4 ), 70.4 (1C, C-4 ), 68.6 (1C, C-4), 66.0 (2C, C-6, C-6 ), 61.8 (1C, C-6 ), 56.5(1C, C-2, J CH = 182 Hz). 6

8 1,2-Anhydro- -D-glucopyranose and its derivatives whose 6-H is substituted by an imidazoliniumoxy group 1 H NMR H Cl - N + N 13 C NMR 7

9 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 8

10 H-H CSY HSQC 9

11 HSQC-TCSY 10

12 1,2-Anhydro- -D-glucopyranose (Dehydrating agent: CDMBI) 1 H NMR 13 C NMR 11

13 DEPT 135 C2 C1 13 C NMR spectrum without composite pulse decoupling 12

14 H-H CSY HSQC 13

15 HSQC-TCSY 14

16 1,2-Anhydro- -D-mannopyranose 1 H NMR H 13 C NMR 15

17 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 16

18 H-H CSY HSQC 17

19 HSQC-TCSY 18

20 1,2-Anhydro- -D-allopyranose 1 H NMR H 13 C NMR 19

21 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 20

22 H-H CSY HSQC 21

23 HSQC-TCSY 22

24 1,2-Anhydro- -D-galactopyranose 1 H NMR H 13 C NMR 23

25 DEPT135 C1 C2 13 C NMR spectrum without composite pulse decoupling 24

26 H-H CSY HSQC 25

27 HSQC-TCSY 26

28 1,2-Anhydro- -L-rhamnopyranose 1 H NMR H 3 C 13 C NMR 27

29 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 28

30 H-H CSY HSQC 29

31 HSQC-TCSY 30

32 1,2-Anhydro- -D-xylopyranose 1 H NMR 13 C NMR 31

33 DEPT 135 C2 C1 13 C NMR spectrum without composite pulse decoupling 32

34 H-H CSY HSQC 33

35 HSQC-TCSY 34

36 1,2-Anhydro cellobiose 1 H NMR H H H 13 C NMR 35

37 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 36

38 H-H CSY HSQC 37

39 HSQC-TCSY 38

40 1,2-Anhydro lactose 1 H NMR H H H 13 C NMR 39

41 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 40

42 H-H CSY HSQC 41

43 HSQC-TCSY 42

44 1,2-Anhydro xylobiose 1 H NMR H 13 C NMR 43

45 DEPT 135 C2 C1 13 C NMR spectrum without composite pulse decoupling 44

46 H-H CSY HSQC 45

47 HSQC-TCSY 46

48 1,2-Anhydro maltose 1 H NMR H H 13 C NMR 47

49 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 48

50 H-H CSY HSQC 49

51 HSQC-TCSY 50

52 1,2-Anhydro melibiose 1 H NMR H 13 C NMR 51

53 DEPT 135 C2 C1 13 C NMR spectrum without composite pulse decoupling 52

54 H-H CSY HSQC 53

55 HSQC-TCSY 54

56 1,2-Anhydro isomaltotriose 1 H NMR H 13 C NMR 55

57 DEPT 135 C1 C2 13 C NMR spectrum without composite pulse decoupling 56

58 H-H CSY HSQC 57

59 HSQC-TCSY 58