Supplementary Material for Chemical Communications
This journal is © The Royal Society of Chemistry 2004
Zinc-Proline catalyzed pathway for the formation of sugars
Jacob Kofoed, Miguel Machuqueiro, Jean-Louis Reymond* and Tamis Darbre*
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
Fax: +41 31 631 80 57; Tel : +41 31 631 43 70; E-mail: tamis.darbre@ioc.unibe.ch
Supporting Information
General. Chemicals and solvents were purchased in the best possible quality from commercial
suppliers. For thin-layer chromatography (TLC), silica gel plates Merck 60 F254 were used and
compounds were visualized treatment with a solution of phosphomolybdic acid (25g),
Ce(SO4)2H2O) (10g), conc. H2SO4 (60 mL), and H2O (940 mL) followed by heating. Flash
chromatography was performed using silicagel Merck 60 (particle size 0.040-0.063 mm),
Solvents were distilled before use. 1H NMR spectra were recorded on Bruker AVANCE300 (300
MHz) or Bruker DRX500 (500 MHz). Chemical shifts are given in ppm referred to solvent
residual peak. Coupling constants (J) are reported in Hertz (Hz). GC experiments were run on a
MACHERY-NAGEL OPTIMA δ 3 column (30 m × 0.25 mm) with He (0.8 ml/min) as carrier
gas, makeup gas N2 and H2-flame. The temperature gradient was 80-320°C, 10°C/min, injector
temperature 300°C and detector 330°C.
Preparation of the Zinc Complexes. The zinc complexes were prepared as previously described
(M. Machuqueiro and T. Darbre Chem. Commun. 2003, 1090-1091).
Procedure for Sugar Synthesis. A solution of glycolaldehyde (60 mg, 1 mmol) and Zn-amino
acid complex (0.15 mmol) in H2O (5 mL) was stirred for 7 days at room temperature . The
solvent was removed by lyophilization.
Procedure for Cross Aldolisation. A solution of glycolaldehyde (60 mg, 1 mmol),
glyceraldehyde (90 mg, 1 mmol) and Zn-amino acid complex (0.15 mmol) in H2O (5 mL) was
stirred for 7 days at room temperature. The solvent was removed by lyophilization.
General Procudre for Peracetylation of The Sugar Mixture. The dry residue was stirred for 24
h in a mixture of acetic acid (2 mL) and pyridine (2 mL) with DMAP (10 mg), then quenched
with H2O (20 mL) and extracted with CH2Cl2 (3 × 20 mL). The organic phase was extracted with
respectively 1 N HCl (60 mL), brine (60 mL) and H2O (60 mL), dried (Na2SO4) and evaporated
to dryness.
For determination of the tetrose composition by 1H NMR, the crude was chromatographed (1:1
EtOAc/hexane) to give a fraction containing only tetroses.
-S1-
Supplementary Material for Chemical Communications
This journal is © The Royal Society of Chemistry 2004
Determination of tetrose composition by sodium borohydride reduction and peracetylation.
A solution of sugar mixture (500 mg) and NaBH4 (100 mg) in H2O (10 mL) was stirred for 3
hours, treated with acetic acid and lyophilized. The dry residue was stirred for 24 h in a mixture
of acetic acid (3 mL) and pyridine (3 mL) with DMAP (30 mg), then quenched with H2O (20
mL) and extracted with CH2Cl2 (3 × 20 mL). The organic phase was extracted with respectively 1
N HCl (60 mL), brine (60 mL) and H2O (60 mL), dried (Na2SO4) and evaporated to dryness. The
tetritols tetraacetates were separated from the hexitols hexaacetates by flash chromatography (2:1
hexane/ethyl acetate). 1H NMR (CDCl3, 300 MHz) δ 2.04-2.08 (m, 12H, 4 × OAc), 4.03 (m, 1H,
CH2), 4.16 (m, 1H, CH2), 4.30 (m, 2H, CH2), 5.24 (m, 1H, CH), 5.30 (m, 1H, CH). Anal. chiral
GC (240°C, 106 KPa, 1,35 mL/min): tR = 90.7 (meso-erythritol tetraacetate), tR = 109.6 (Dthreitol tetraacetate), tR = 113.8 (L-threitol tetraacetate), ee ~10%. L-threitol tetraacetate was
synthesized as reference for chiral GC and NMR: 1H NMR (CDCl3, 300 MHz) δ 2.09-2.13 (m,
12H, 4 × OAc), 4.08 (m, 2H, CH2), 4.36 (m, 2H, CH2), 5.35 (m, 2H, CH). Anal. chiral GC
(240°C, 106 KPa, 1,35 mL/min): tR = 114.7.
NMR and GC spectra.
tetroses
hexoses
Figure S1. GC of the peracetylated crude sugar mixture showing the tetrose and hexose regions.
-S2-
Supplementary Material for Chemical Communications
This journal is © The Royal Society of Chemistry 2004
β-threose
α-threose
β-erythrose
Figure S2. GC of the peracetylated crude sugar mixture showing α-threose, β-threose and β –
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
(ppm)
4.5
4.0
32.517
1.0503
1.8681
3.3902
1.0935
3.9561
0.3432
1.0142
0.9642
0.6899
0.0437
1.0000
Integral
erythrose.
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Figure S3. 1H NMR (500 MHz) in D2O of the tetrose acetate mixture showing α-threose, βthreose and β-erythrose, after chromatography
-S3-
β-erythrose
6.44
6.40
6.36
6.32
6.28
6.24
6.20
(ppm)
6.16
6.12
0.9642
α-threose
0.6899
0.0437
1.0000
Integral
β-threose
6.48
2426.15
2448.49
2446.73
2511.73
2516.25
2535.07
2539.59
Supplementary Material for Chemical Communications
This journal is © The Royal Society of Chemistry 2004
6.08
6.04
6.00
5.96
5.92
Figure S3. 1H NMR (D2O, 500 MHz) showing the anomeric protons of α-threose, β-threose and
β-erythrose.
Glucose
Galactose
Talose
Figure S4. GC of commercial, equilibrated, peracetylated hexoses (Glucose, Galactose and
Talose) and (below) of the crude peracetylated mixture showing the hexose region.
-S4-
Supplementary Material for Chemical Communications
This journal is © The Royal Society of Chemistry 2004
4.2
(ppm)
0.8310
1.0905
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
(ppm)
2.0877
2.0732
2.0488
2.0456
12.167
(ppm)
1.9841
1.1425
0.8442
4.3
(ppm)
4.3419
4.3287
4.3237
4.3023
4.2891
4.2829
4.1994
4.1818
4.1586
4.1404
4.0695
4.0500
4.0293
4.0105
0.8442
1221.58
1215.74
1209.53
1203.87
1260.58
1255.30
1248.33
1242.87
1.1425
1.9841
1299.38
1297.88
1291.47
1287.52
1285.63
1575.93
1573.29
1570.84
5.2
(ppm)
Integral
5.30
(ppm)
1.9841
0.8310
1.0905
1597.02
1593.26
1589.30
5.3202
5.3077
5.2945
5.2499
5.2411
5.2330
jk-128-C4-O-acetyl.red.sugar (mix of isomers)Proton_ns32 CDCl3 /disk0 service 60
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Figure S5. 1H NMR (CHCl3, 300 MHz) of tetrol peracetates.
Reference L-Threitol tetraacetate
Reduced and acetylated tetrol mixture
Figure S6. Chiral GC trace of reduced and acetylated tetrols showing the meso-erythritol and the
two enantiomers of threitol.
-S5-
Supplementary Material for Chemical Communications
This journal is © The Royal Society of Chemistry 2004
Table S1. 1H NMR (D2O, 300 MHz) chemical shifts (δ) and coupling constants (J) of
anomeric protons in commercial, equilibrated pentoses and comparison with the values
obtained from the crossaldolisation reaction between glycolaldehyde and glyceraldehyde.
Entry
Pentose
Aunthentic samples
Experimental values
δ (ppm)
J (Hz)
δ (ppm)
J (Hz)
α, β
α, β
α, β
α, β
(%)
Calc. pentose
distribution
1
Arabinose
4.43, 5.14
7.73, 3.39
4.42, 5.14
7.72, 3.58
~20
2
Lyxose
4.92, 4.77
4.42, 1.51
4.92, n.d.
4.52, n.d.*
~30
3
Ribose
4.84, 4.79
6.41, 2.08
4.83, n.d.
6.60, n.d.*
~35
4
Xylose
5.11, 4.49
3.77, 7.91
5.11, 4.48
3.57, 7.72
~15
*not detected – hidden under the solvent residual peak (H2O).
-S6-