Supporting Information

Synthesis, Biological Activity and Molecular

Modeling Studies of 1H-1,2,3-Triazoles
Derivatives of Carbohydrates as Inhibitors
of α-Glucosidases

Sabrina B. Ferreira†, Ana C. R. Soderoψ, Mariana F. C. Cardoso‡, Emerson S. Lima¥,

Carlos R. Kaiser†, Floriano P. Silva Jrψ, and Vitor F. Ferreira*‡

Table of Contents:

1. Preparation and spectroscopic data of the azido derivatives, and the

precursors derivatives.
2. 1H- and 13C-NMR spectra of the new target compounds

3. Mass spectra of the new target compounds

S1
1. Preparation and Spectroscopic data of the azido derivatives, and the precursors
derivatives.

1-O-methyl-2,3-O-isopropylidene-β-D-ribofuranose.1 To a solution of D-ribose

(1.0 g, 5.0 mmol) in dry acetone (5.0 mL) and dry methanol (5.0 mL), sulfuric acid
conc. (0.5 mL) was slowly added. The stirred mixture was kept for 48 h, under nitrogen
at room temperature, and the reaction was quenched with NaHCO3 to neutralize the
solution. The resulting mixture was filtered under vacuum and evaporated to a reduced
volume. The resulting residue was dissolved with ethyl acetate (50 mL) and washed
with water (3 x 50 mL). After drying over anhydrous sodium sulfate, the solvent was
removed under reduced pressure to leave the product as yellow oil in 95% yield (1.30
g). IR (film, CHCl3) ν(cm-1): 3453, 1374 and 1382; 1H NMR (CDCl3, 300 MHz) δ 1.32
(s, 3H, CH3), 1.49 (s, 3H, CH3), 3.43 (s, 3H, OCH3), 3.61 (dd, 1H, J = 3.7 and 12.5 Hz,
H-5), 3.69 (dd, 1H, J = 2.7 and 12.5 Hz, H-5’), 4.42 (t, 1H, J = 2.9 Hz, H-4), 4.59 (d,
13
1H, J = 6.1 Hz, H-2), 4.83 (d, 1H, J = 6.1 Hz, H-3), 4.97 (s, 1H, H-1); C NMR
(CDCl3, 75 MHz) δ 24.5 (CH3), 26.1 (CH3), 55.2 (OCH3), 63.7 (C-5), 81.3 (C-3), 85.6
(C-2), 88.1 (C-4), 109.7 (C-1), 111.9 (C-6).

1-O-methyl -2,3-O-isopropylidene-5-O-methanesulfonyl-β-D-ribofuranose.2 A
solution of 1-O-methyl-2,3-O-isopropylidene-β-D-ribofuranose (1.0 g, 4.90 mmol) in
15 mL ethyl acetate and 2.4 mL of pyridine was stirred and heated at 120°C under
nitrogen atmosphere. Next, a second solution of mesyl chloride (1.48 g, 12.92 mmol)
dissolved in 15 mL of ethyl acetate was added slowly. The reaction was kept under
stirring during four hours. Then, the solution was cooled to r.t. and extracted with cold
water (3x30 mL). The organic phase was washed with a solution of hydrochloric acid
50% (10 mL), aqueous solution of CuSO4 (10% w/v), saturated solution of sodium
bicarbonate and dried with anhydrous sodium sulfate. After filtration and evaporation of
the solvent, the residue was purified by silica gel column chromatography using a
mixture of hexane / ethyl acetate 9:1 as eluent. The product was isolated in 65% (897
mg) as a light yellow solid. M.p. 68-69 °C (lit. 70-71°C). IR (film, CHCl3) ν(cm-1):
1350, 1170 and 1380; 1H NMR (CDCl3, 300 MHz) δ 1.33 (s, 3H, H-7), 1.49 (s, 3H, H-
8), 3.07 (s, 3H, CH3SO3), 3.35 (s, 3H, H-6), 4.21 (dd, 1H, J= 1.2 and 7.5 Hz, H-5), 4.21

S2
(dd, 1H, J= 1.2 and 7.5 Hz, H-5´), 4.39-4.44 (m, 1H, H-4), 4.61 (d, 1H, J = 6.0 Hz, H-
13
2), 4.71 (dd, 1H, J = 0.9 and 6.0 Hz, H-3), 4.99 (s, 1H, H-1); C NMR (CDCl3, 75
MHz) δ 24.8 (CH3), 26.3 (CH3), 37.6 (CH3SO2), 55.1 (OCH3), 68.3 (C-5), 81.2 (C-3),
83.7 (C-4), 84.8 (C-2), 109.4 (C-1), 112.7 (C-6).

β-D-ribofuranose.3 To a
1-O-methyl-2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β
solution of 1-O-methyl-2,3-O-isopropylidene-β-D-ribofuranose (4.5 g, 0.022 mol) in
dry pyridine (8.5 mL), externally cooled with ice, was added p-toluenesulfonyl chloride
(5.3 g, 0.027 mol) and catalytic amount of DMAP. The reaction mixture was stirred at
room temperature under nitrogen atmosphere for five hours. After this time, 2 mL of
distilled water was added and the stirring was kept for more 30 minutes. This mixture
was extracted with chloroform (3x25 mL) and the combined organic phases was washed
with aqueous solution of CuSO4 (10% w/v), saturated solution of NaHCO3, water and
dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure
furnished a white powder (90%, 7.09 g) with m.p. 85-86 °C (lit.51 84-85 °C). IR (film,
CHCl3) ν(cm-1): 1358 and 1180; 1H NMR (CDCl3, 300 MHz) δ 1.29 (s, 3H, CH3), 1.45
(s, 3H, CH3), 2.46 (s, 3H, CH3-aryl), 3.24 (3H, s, OCH3), 4.02 (dd, 2H, J= 1.5 and 7.5
Hz, H-5 and H-5’), 4.31 (ddd, 1H, J= 0.6, 6.9 and 7.2 Hz, H-4), 4.53 (d, 1H, J= 6.0 Hz,
H-2), 4.60 (dd, 1H, J= 0.3 and 5.7 Hz, H-3), 4.93 (s, 1H, H-1), 7.36 (dd, 2H, J= 0.3 and
13
8.7 Hz, H-3´), 7.81 (dd, 2H, J= 0.6 and 8.7 Hz, H-2´); C NMR (CDCl3, 75 MHz) δ
21.5 (CH3-aryl), 24.7 and 26.2 (2 x CH3), 54.9 (OCH3), 69.1 (C-5), 81.2 (C-3), 83.4 (C-
4), 84.7 (C-2), 109.3 (C-1), 112.6 (C-6), 127.8 (C-2´), 129.8 (C-3´), 132.6 (C-4´), 144.9
(C-1´).

β -D-ribofuranose.4
1-O-methyl-5-azido-5-deoxy-2,3-O-isopropylidene-β To a
solution 1-O-methyl-2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-ribofuranose
(700 mg, 2.48 mmol) in dry DMF (7 mL) was added sodium azide (1.96 g, 30.15
mmol). The mixture was heated at 120 0C for 12 hours and monitored by tlc (hexane /
ethyl acetate 7:3). After cooling, acetone (10 mL) was added to this mixture and then
filtrated under vacuum. The solvent was removed under reduced pressure furnishing an
oil that was dissolved 50 mL of chloroform and washed with water (50 mL), saturated
solution of NaHCO3 (50 mL) and water (50 mL). The resulting solution was dried with
anhydrous sodium sulfate, filtrated and evaporated furnishing a yellow liquid (95%, 540
S3
mg). IR (film, CHCl3) ν(cm-1): 2113 and 1377; 1H NMR (CDCl3, 300 MHz) δ 1.31 (d,
3H, J = 0.6 Hz, CH3), 1.47 (d, 3H, J = 0.6 Hz, CH3), 3.32 (s, 3H, OCH3), 3.54 (dd, 1H,
J = 10.9 and 5.9 Hz, H-5), 3.45 (dd, 1H, J = 10.9 and 5.9 Hz, H-5’), 4.30 (td, 1H, J =
5.9 and 0.6 Hz, H-4), 4.59 (dd, 1H, J = 5.9 and 0.6 Hz, H-2), 4.72 (dd, 1H, J = 5.9 and
0.6 Hz, H-3), 4.97 (s, 1H, H-1); 13C NMR (CDCl3, 75 MHz) δ 24.8 (CH3), 26.3 (CH3),
55.1 (OCH3), 53.7 (C-5), 81.9 (C-3), 85.0 (C-2 or C-4), 85.3 (C-2 or C-4), 109.7 (C-1),
112.6 (C-6).

1,2:3,4-di-O-isopropylidene-α-D-galactopyranose.1,5 In a round-bottomed flask

containing of D-galactose (9.0 g, 50 mmol), acetone (200 mL) and of anhydrous CuSO4
(20.0 g, 125 mmol) was added dropwise concentrated sulfuric acid (1.0 mL). The
mixture was stirred for 24 hours and then filtered under vacuum. The liquid was
neutralized with NaHCO3, filtrated and the solvent removed under vacuum resulting an
oil that was dissolved in 100 mL of ethyl acetate. This solution was washed with water
(3 x 50 mL), dried with anhydrous sodium sulfate, filtrated and evaporated under
reduced pressure producing a yellowish oil (80%, 10.4 g). IR (film, CHCl3) ν(cm-1):
3466 and 1383; 1H NMR (CDCl3, 300 MHz) δ 1.34 (s, 6H, CH3), 1.35 (s, 6H, CH3),
1.46 (s, 3H, CH3), 1.54 (s, 3H, CH3), 3.90-3.81 (m, 1H, H-5), 3.90- 3.81 (m, 2H, H-6
and H-6´), 4.28 (dd, 1H, J = 7.8 and 1.5 Hz, H-4), 4.34 (dd, 1H, J = 5.1 and 2.4 Hz, H-
13
2), 4.62 (dd, 1H, J= 2.4 and 7.8 Hz, H-3), 5.58 (d, 1H, J = 5.1 Hz, H-1); C NMR
(CDCl3, 75 MHz) δ 24.1 (CH3), 24.7 (CH3), 25.7 (CH3), 25.8 (CH3), 61.9 (C-6), 68.0
(C-5), 70.3 (C-2), 70.5 (C-3), 71.3 (C-4), 96.1 (C-1), 109.2 (C-7), 108.5 (C-8).

α-D-galactopyranose.5
1,2:3,4-di-O-isopropylidene-6-O-p-toluenesulfonyl-α In a
round-bottomed flask externally cooled by were added of 1,2:3,4-di-O-isopropylidene-
α-D-galactopyranose (5.0 g, 19.2 mmol) and anhydrous pyridine (30 mL). Then were
added p-toluenesulfonyl chloride (11.1 g, 58.2 mmol) and catalytic amount of DMAP.
The mixture was stirred at room temperature and monitored by tlc (eluent: hexane/ethyl
acetate 8:2) for 16 hours. Next, were added cold water (50 mL) and dichloromethane
(50 mL) and the organic phase was separated and washed with aqueous solution of
CuSO4 (10% w/v), saturated solution of sodium bicarbonate and then with distilled
water. The organic phase was dried with sodium sulfate and concentrated at reduced
pressure, yielding light yellow oil, which the product crystallized as a white solid (75%,
S4
5.97 g) upon addition of isopropyl alcohol. M.p. 89-90 °C (lit.5 91-92 °C). IR (film,
CHCl3) ν(cm-1): 1355, 1190 and 900; 1H NMR (CDCl3, 300 MHz) δ 1.30 (s, 3H, CH3),
1.33 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.52 (s, 3H, CH3), 2.46 (s, 3H, CH3- aryl), 4.13-
4.04 (m, 2H, H-6 and H-6´), 4.24-4.19 (m, 2H, H-4 and H-5), 4.31 (dd, 1H, J= 2.7 and
5.1 Hz, H-2), 4.60 (dd, 1H, J= 2.7 and 7.8 Hz, H-3), 5.47 (d, 1H, J= 5.1 Hz, H-1), 7.35
13
(dd, 1H, J= 0.6 and 8.7 Hz, H-2’), 7.82 (dd, 1H, J= 1.5 and 6.6 Hz, H-1’); C NMR
(CDCl3, 75 MHz) δ 21.5 (H3C-C-arom), 25.8, 25.7, 24.8, 24.2 (4 x CH3), 65.8 (C-5),
68.1 (C-6), 70.2 (C-2, C-3 or C-4), 70.3 (C-2, C-3 or C-4), 70.4 (C-2, C-3 or C-4), 96.0
(C-1), 109.4 and 108.8 [C-7 and C-8 C(CH3)2], 129.6 and 128.0 (C H arom.), 132.7
(H3C-C-arom.), 144.6 (C-SO3).

α-D-galactopyranose.4 A solution of 1,2:3,4-

1,2:3,4-di-O-isopropylidene-6-azido-α
di-O-isopropylidene-6-O-p-toluenesulfonyl-α-D-galactopyranose (2.0 g 4.8 mmol) in
DMF (20 mL) was added sodium azide (2.18 g, 33.6 mmol). The mixture was stirred
and monitored by tlc (hexane / ethyl acetate 7:3) at 1100C for 24 hours. After this time,
the mixture was filtrated and the liquid concentrated under reduced pressure funnishing
an oil, which was dissolved in chloroform (50 mL) and washed with water (3x 20 mL).
The organic phase was dried with anhydrous sodium sulfate and the residue purified by
silica gel column chromatography using a mixture of hexane / ethyl acetate 9:1 as
eluent. The product was obtained as light yellow oil (85%, 1.1 g). IR (film, CHCl3)
ν(cm-1): 2104; 1H NMR (CDCl3, 300 MHz) δ 1.34 (s, 3H, CH3), 1.35 (s, 3H, CH3), 1.46
(s, 3H, CH3), 1.55 (s, 3H, CH3), 3.38 (dd, 1H, J= 5.4 and 12.9 Hz, H-6´), 3.53 (dd, 1H,
J= 7.8 and 12.6 Hz, H-6), 3.93 (DDD, 1H, J= 1.8, 5.4 and 7.8 Hz, H-5), 4.21 (dd, 1H,
J= 2.1 and 7.8, H-4), 4.35 (dd, 1H, J= 2.4 and 5.1 Hz, H-2), 4.65 (dd, 1H, J= 2.4 and 7.8
Hz, H-3), 5.55 (d, 1H, J= 5.1 Hz, H-1); 13C NMR (CDCl3, 75 MHz) δ 24.3, 24.8, 25.8,
25.9 (4 x CH3), 50.5 (C-6), 66.9 (C-5), 70.3 (C-2, C-3 or C-4), 70.7 (C-2, C-3 or C-4),
71.0 (C-2, C-3 or C-4), 96.2 (C-1), 109.5 and 108.7 [C-7 and C-8 C(CH3)2].

1,2:5,6-di-O-isopropylidene-α-D-glucofuranose.1 In a round bottom flask, was

added a solution of D-Glucose (10 g, 56.0 mmol), dry acetone (500 mL) and iodine
(700 mg). The mixture was kept under magnetic stirring and reflux for 6 hours. Then,
the mixture was cooled to room temperature and was added a aqueous solution sodium
thiosulfate (0.5 M) until discoloration of the medium. After evaporation of the solvent
S5
the solution was extracted with dichloromethane (3 x 100 mL) and the organic phases
were combined and the resulting solution was washed with water and was dried with
anhydrous sodium sulfate. The product was recrystallized with hot hexane and activated
charcoal. It was obtained the product as a white crystals (80%, 11.6 g). M.p 109-110 °C
(lit.6 107-108 ºC). IR (film, CHCl3) ν(cm-1): 3475; 1H NMR (CDCl3, 300 MHz) δ 1.32
(s, 3H, CH3), 1.36 (s, 3H, CH3), 1.45 (s, 3H, CH3), 1.50 (s, 3H, CH3), 2.65 (d, 1H, J =
3.4 Hz, OH), 3.99 (dd, 1H, J = 5.4 and 8.5 Hz, H-6), 4.07 (dd, 1H, J = 2.7 and 7.6 Hz,
H-4), 4.17 (dd, 1H, J = 6.1 and 8.5 Hz, H-6’), 4.31 (d, 1H, J = 2.9 Hz, H-3), 4.35 (ddd,
1H, J = 5.4, 6.1 and 7.8 Hz, H-5), 4.53 (d, 1H, J = 3.7 Hz, H-2), 5.94 (d, 1H, J = 3.7
13
Hz, H-1); C NMR (CDCl3, 75 MHz) δ 25.1 (CH3), 26.1 (CH3), 26.6 (CH3), 26.7
(CH3), 67.5 (C-6), 73.1 (C-5), 74.7 (C-4), 81.0 (C-3), 85.0 (C-2), 105.1 (C-1), 109.5 (C-
8), 111.7 (C-7).

1,2:5,6-di-O-isopropylidene-α-D-allofuranose.7,8 In a round bottom flask flushed

with argon were added oxyaly chloride (5.0 mL, 57.2 mmol) and dry CH2Cl2 (70 mL)
and then cooled to -80 °C. To this solution was slowly added a mixture of DMSO (8.2
mL, 115.3 mmol) and dry CH2Cl2 (20 mL) drop by drop, for a period of 20 min. The
reaction mixture was stirred for 15 min and added dropwise a solution of 1,2:5,6-di-O-
isopropylidene-α-D-glucofuranose (5 g,19.2 mmol) in of dry CH2Cl2 (150 mL). The
reaction mixture was stirred for 90 min and added dropwise triethylamine (20.2 mL,
144.6 mmol). The mixture was kept at -80 ºC and then added of NaBH4 (1.45 g, 38.8
mmol) dissolved in EtOH/H2O (8:2, 100 mL). During the addition the temperature was
kept between -60 to -40 º C. The mixture was allowed to reach room temperature and
then was added a aqueous saturated solution of NaCl (150 mL). The resulting mixture
was extracted with CH2Cl2 (3 x 100 mL) and the organic phase was washed with
distilled water (3 x 100 mL) and was dried with anhydrous Na2SO4. Evaporation of the
solvent under reduced pressure in rotatory evaporator led to the product as white
crystals (98%, 7.10 g). M.p. 75-77 °C (lit.5577-78 ºC). IR (film, CHCl3) ν(cm-1): 3470
and 1370; 1H NMR (CDCl3, 300 MHz) δ 1.38 (s, 3H, CH3), 1.39 (s, 3H, CH3), 1.47 (s,
3H, CH3), 1.58 (s, 3H, CH3), 2.55 (d, 1H, J = 8.7 Hz, OH), 3.82 (dd, 1H, J = 4.8, 8.4
Hz, H-4), 4.12-4.00 (m, 3H, H-3, H-6 and H-6´), 4.31 (dt, 1H, J = 4.8, 6.6 Hz, H-5),
4.62 (dd, 1H, J = 3.9, 5.2 Hz, H-2), 5.82 (d, 1H, J = 3.9 Hz, H-1); 13C NMR (CDCl3, 75

S6
MHz) δ 25.0 (CH3), 26.0 (CH3), 26.2 (CH3), 26.3 (CH3), 65.5 (C-6), 72.2 (C-3), 75.3
(C-5), 78.7 (C-2), 79.4 (C-4), 103.6 (C-1), 109.5 (C-8), 112.5 (C-7).

α-D-allofuranose.2 In a round
3-methanosulfonyl-1,2:5,6-di-O-isopropylidene-α
bottom flask containing a solution of 1,2:5,6-di-O-isopropylidene-α-D-allofuranose
(400 mg, 1.54mmol) in dichloromethane (20 mL) under argon was added catalytic
amount of DMAP and of triethylamine (2 mL). The misture was stirred for 10 minutes
and added mesyl chloride (0.7 mL, 4.62 mmol). The mixture was kept stirred at room
temperature for 8 h. To this mixture was added of dichloromethane (10 mL) and
successive extracted with cold water (10 mL), a solution of HCl 5% (10 mL) and
subsequent drying with anhydrous sodium sulfate. After filtration and evaporation of
the solvent, the product was purified by silica gel column chromatography using
hexane/ethyl acetate (7:3) as eluente furnishing the product as pale yellow solid (65%,
337 mg). M.p 124-125 ºC (lit.123-125 ºC). with a yield of 1H NMR (CDCl3, 300 MHz)
δ 1.36 (s, 3H, CH3), 1.37 (s, 3H, CH3), 1.47 (s, 3H, CH3), 1.57 (s, 3H, CH3), 3.13 (s,
3H, CH3SO3), 3.91 (dd, 1H, J = 5.6, 8.5 Hz, H-6 or H-6´), 4.07 (dd, 1H, J = 6.1, 8.5
Hz, H-6 or H-6´), 4.12 (ddd, 1H, J = 4.6, 5.8, 6.5 Hz, H-2), 4.32 (ddd, 1H, J = 4.3, 5.6,
6.5 Hz, H-5), 4.78 (d, 1H, J = 1.5 Hz, H-3), 4.81 (dd, 1H, J = 4.8, 8.7 Hz, H-4), 5.81
(dd, 1H, J = 1.5, 3.7 Hz, H-1); 13C NMR (CDCl3, 75 MHz) δ 24.7 (CH3), 26.0 (CH3),
26.4 (CH3), 26.4 (CH3), 38.6 (CH3SO2), 65.3 (C-6), 74.5 (C-3), 76.7 (C-5), 76.8 (C-2),
77.7 (C-4), 103.7 (C-1), 109.9 (C-8), 113.5 (C-7).

α-D-allofuranose.4Error!
3-azido-1,2:5,6-di-O-isopropylidene-α Bookmark not defined.
In a
round bottom flask containing a solution of 3-metanosulfonil-1,2:5,6-di-O-
isopropylidene-α-D-allofuranose (200 mg, 0.6 mmol) in dry DMF(6 mL) under
nitrogen was added sodium azide (468 mg, 7.2 mmol) and the reaction was heated
under reflux for 2 days. The mixture was allowed to cool to room temperature, added
acetone (10 mL). filtrated and the liquid concentrated under reduced pressure. The
residue was purified by silica gel column chromatography using hexane/ethyl acetate
(98%) as the eluente. The product was obtained as a pale yellow oil (46%, 78 mg). IR
(film, CHCl3) ν(cm-1): 2109; 1H NMR (CDCl3, 300 MHz) δ 1.32 (s, 3H, CH3), 1.36 (s,
3H, CH3), 1.43 (s, 3H, CH3), 1.51 (s, 3H, CH3), 3.97 (ddd, 1H, J = 3.6, 4.8, 8.5 Hz, H-
6 or H-6´), 4.09 (dd, 1H, J = 1.7, 3.6 Hz, H-6 or H-6´), 4.10 (d, 1H, J = 2.4 Hz, H-4),
S7
4.15 (dd, 1H, J = 2.4, 8.5 Hz, H-3), 4.25 (ddd, 1H, J = 1.4, 4.8, 7.0 Hz, H-5), 4.61 (d,
1H, J = 3.6 Hz, H-2), 5.85 (d, 1H, J = 3.4 Hz, H-1); 13C NMR (CDCl3, 75 MHz) δ 24.9
(CH3), 26.0 (CH3), 26.4 (CH3), 26.6 (CH3), 66.2 (C-3), 67.4 (C-6), 72.8 (C-5), 80.3
(C-2), 83.2 (C-4), 104.8 (C-1), 109.3 (C-8), 112.1 (C-7).

α-D-xilofuranose.9 In a round-bottomed flask flushed

1,2:3,5-di-O-isopropylidene-α
with nitrogen and externally cooled with ice were added D-xylose (10 g, 0,067 mol),
anhydrous acetone (300 mL), anhydrous CuSO4 (26 g) and concentrated sulfuric acid (2
mL). The mixture was stirred at room temperature for 24 hours. After this time, the
mixture was filtrated and neutralized with saturated solution of calcium carbonate. This
mixture was filtrated and concentrated under resulting pressure furnishing an oil, which
was then extracted with dichloromethane. The organic phase was dried with anhydrous
sodium sulphate, filtered and the solvent was evaporated yielding the product as a
colorless syrup (85%, 8.5 g). IR (film, CHCl3) ν(cm-1): 1381; 1H NMR (CDCl3, 300
MHz) δ 1.33 (s, 3H, CH3), 1.39 (s, 3H, CH3), 1.45 (s, 3H, CH3), 1.50 (s, 3H, CH3),
4.02-4.10 (m, 3H, H-4, H-5 and H-6), 4.30 (d, 1H, J= 2.4 Hz, H-3), 4.52 (d, 1H, J= 3.6
Hz, H-2), 6.00 (d, 1H, J= 3.9 Hz, H-1); 13C NMR (CDCl3, 75 MHz) δ 18.5 (CH3), 26.0
(CH3), 26.6 (CH3), 28.8 (CH3), 60.0 (C-5), 71.5 (C-3 or C-4), 73.1 (C-3 or C-4), 84.4
(C-2), 105.1 (C-1), 111.5 and 97.4 (C-6 e C-7).

α-D-xilofuranose.10 In a round-bottomed flask containing

1,2-O-isopropylidene-α
1,2:3,5-di-O-isopropylidene-α-D-xilofuranose (19 g, 0.082 mmol) was added a solution
of hydrochloric acid (0.2 mL) in water (100 mL). The reaction medium was kept under
stirring for 3 hours at room temperature. After this time, the solution was neutralized
with sodium bicarbonate, filtered, washed with acetone and the filtrate concentrated.
Then, the oil obtained was purified by silica gel column chromatography using hexane /
acetate 7:3 (1:1) as eluent yielding the product as colorless oil (60%, 7.0 g). IR (film,
CHCl3) ν(cm-1): 3391 and 1074; 1H NMR (CDCl3, 300 MHz) δ 5.99 (d, 1H, J= 3.7 Hz,
H-1), 4.52 (d, 1H, J= 3.7 Hz, H-2), 4.29 (s, 1H, H-3), 4.17-4.20 (m, 1H, H-4), 3.98-4.10
(m, 2H, H-5 and H-5’), 1.49 and 1.33 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz) δ 26.1
(CH3), 26.6 (CH3), 60.7 (C-5), 76.4 (C-3), 79.0 (C-4), 85.4 (C-2), 104.7 (C-1), 111.7
(C-6).

S8
 α-D-xilofuranose.8
5-O-p-toluenosulfonyl-1,2-O-isopropilideno-α In a round-
bottomed flask flushed with nitrogen and externally cooled with ice were added 1,2-O-
isopropylidene-α-D-xilofuranose (5.0 g, 0.026 mmol) was added of dry pyridine (20
mL). Then, it was added dropwise a solution of tosyl chloride (5.5 g, 0.028 mmol) in
dissolved in dry pyridine. After 1 h, the temperature was raised to room temperature and
the reaction mixture was stirred for an additional 24 h and was treated with water (50
mL). The mixture was extracted with chloroform (3x50 mL) and the extracts washed
with 50% HCl solution, saturated solution of sodium bicarbonate and water,
respectively. The combined organic layer was dried over CaSO4, filtered, and
concentrated under reduced pressure resulting in a syrup that upon washing with ethyl
ether gave the product as white solid (51%, 2.5 g). M.p. 130-131°C (lit.Error! Bookmark not
defined.
133-134 °C). IR (film, CHCl3) ν(cm-1): 3434 and 1360; 1H NMR (CDCl3, 300
MHz) δ 1.46 (s, 3H, CH3), 1.30 (s, 3H, CH3), 2.46 (s, 3H, CH3-aryl), 4.10-4.18 (m, 1H,
H-3), 4.29-4.35 (m, 3H, H-4, H-5 and H-5’), 4.51 (d, 1H, J= 3.4 Hz, H-2), 5.88 (d, 1H,
J= 3.4 Hz, H-1), 7.36 (ddd, 2H, J= 8.1, 0.7 and 0.7 Hz, H-2’), 7.81 (ddd, 2H, J= 8.3, 1.9
13
and 1.7 Hz, H-1’); C NMR (CDCl3, 75 MHz) δ 21.6 (CH3-aryl), 26.1 (CH3), 26.7
(CH3), 66.5 (C-5), 74.2 (C-3), 77.6 (C-4), 85.0 (C-2), 104.9 (C-1), 112.0 (C-6), 129.9
and 127.9 (CH arom.-1´ or 2´), 132.2 (Car-CH3), 145.2 (C-SO2-O).

α-D-xilofuranose.4 To a solution of 5-O-p-

5-deoxy-5-azido-1,2-O-isopropylidene-α
toluenosulfonyl-1,2-O-isopropilideno-α-D-xilofuranose (1.0 g, 2.90 mmol) in 10 mL of
dry DMF was added of sodium azide (1.13 g 17.4 mmol) and the mixture heated at 120o
C for 20 h under nitrogen atmosphere. The mixture was cooled to room temperature,
dissolved in acetone (20 mL), filtrated and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography using a mixture of eluents
hexane / ethyl acetate (98%) giving a yellowish liquid (85%, 0.51 g). IR (film, CHCl3) ν
(cm-1): 2099 and 3404; 1H NMR (CDCl3, 300 MHz) δ 1.34 (s, 3H, CH3), 1.51 (s, 3H,
CH3), 2.32 (sl, 1H, OH), 3.64-3.61 (m, 2H, H-5 and H-5´), 4.33-4.26 (m, 2H, H-3 and
H-4), 4.54 (d, 1H, J= 3.9 Hz, H-2), 5.97 (d, 1H, J= 3.6 Hz, H-1); 13C NMR (CDCl3, 75

S9
MHz) δ 27.0 (CH3), 26.4 (CH3), 49.4 (C5), 75.5 (C-3 or C-4), 78.5 (C-3 or C-4), 85.6
(C-2), 105.0 (C-1), 112.3 (C-6).
2. 1H- and 13C-NMR spectra of the new target compounds:

1-O-methyl-2,3-O-isopropylidene-5-(4-phenyl-1H-1,2,3-triazol-1-yl)-β-D-ribofuranose (4a).

S10
1-O-methyl-2,3-O-isopropylidene-5-(4-cyclohexene-1H-1,2,3-triazol-1-yl)-β-D-ribofuranose
(4b).

S11
1-O-methyl-2,3-O-isopropylidene-5-(4-hydroxymethyl-1H-1,2,3-triazol-1-yl)-β-D-
ribofuranose (4c).

S12
1-O-methyl-2,3-O-isopropylidene-5-(4-carboxylate ethyl-1H-1,2,3-triazol-1-yl)-β-D-
ribofuranose (4d).

S13
1-O-methyl-2,3-O-isopropylidene-5-(4-phenoxymethyl-1H-1,2,3-triazol-1-yl)-β-D-
ribofuranose (4e).

S14
1-O-methyl-2,3-O-isopropylidene-5-[4-(3-chloropropyl)-1H-1,2,3-triazol-1-yl]-β-D-
ribofuranose (4f).

S15
1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxycyclohexil)-1H-1,2,3-triazol-1-yl]-β-D-
ribofuranose (4g).

S16
1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxy-1-methylethyl)-1H-1,2,3-triazol-1-yl]-β-
D-ribofuranose (4h).

S17
1-O-methyl-2,3-O-isopropylidene-5-(4-propyl-1H-1,2,3-triazol-1-yl)-β-D-ribofuranose (4i).

S18
1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxy-1-methylpropyl)-1H-1,2,3-triazol-1-yl]-
β-D-ribofuranose (4j).

S19
1-O-methyl-2,3-O-isopropylidene-5-(4-methylacetate-1H-1,2,3-triazole-1-yl)-β-D-
ribofuranose (4l).

S20
1-O-methyl-2,3-O-isopropylidene-5-[4-(tetrahydro-2H-pyran)methyl)-1H-1,2,3-triazole-1-
yl]-β-D-ribofuranose (4m).

S21
1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxy-1,3-dimethylbutyl)-1H-1,2,3-triazole-1-
yl]-β-D-ribofuranose (4n).

S22
1,2:3,4-di-O-isopropylidene-6-(4-phenyl-1H-1,2,3-triazole-1-yl)-α-D-galactopyranose. (5a).

S23
1,2:5,6-di-O-isopropylidene-3-(4-phenyl-1H-1,2,3-triazole-1-yl)-α-D-alofuranose (6a).

S24
 α-D-xilofuranose
5-deoxy-1,2-O-isopropylidene-5-(4-phenyl-1H-1,2,3-triazole-1-yl)-α (7a).

S25
 α-D-
5-deoxy-1,2-O-isopropylidene-5-[4-(1-cyclohexene)-1H-1,2,3-triazole-1-yl]-α
xilofuranose (7b).

S26
 α-D-
5-deoxy-1,2-O-isopropylidene-5-(4-hydroxymethyl-1H-1,2,3-triazole-1-yl)-α
xilofuranose (7c).

S27
3. Mass spectra of the new target compounds:

1-O-methyl-2,3-O-isopropylidene-5-(4-phenyl-1H-1,2,3-triazol-1-yl)-β-D-ribofuranose (4a).

1-O-methyl-2,3-O-isopropylidene-5-(4-cyclohexene-1H-1,2,3-triazol-1-yl)-β-D-ribofuranose
(4b).

S28
1-O-methyl-2,3-O-isopropylidene-5-(4-hydroxymethyl-1H-1,2,3-triazol-1-yl)-β-D-
ribofuranose (4c).

1-O-methyl-2,3-O-isopropylidene-5-(4-carboxylate ethyl-1H-1,2,3-triazol-1-yl)-β-D-
ribofuranose (4d).

S29
1-O-methyl-2,3-O-isopropylidene-5-(4-phenoxymethyl-1H-1,2,3-triazol-1-yl)-β-D-
ribofuranose (4e).

1-O-methyl-2,3-O-isopropylidene-5-[4-(3-chloropropyl)-1H-1,2,3-triazol-1-yl]-β-D-
ribofuranose (4f).

S30
1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxycyclohexil)-1H-1,2,3-triazol-1-yl]-β-D-
ribofuranose (4g).

1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxy-1-methylethyl)-1H-1,2,3-triazol-1-yl]-β-
D-ribofuranose (4h).

S31
1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxy-1-methylpropyl)-1H-1,2,3-triazol-1-yl]-β-D-
ribofuranose (4j).

1-O-methyl-2,3-O-isopropylidene-5-(4-methylacetate-1H-1,2,3-triazole-1-yl)-β-D-
ribofuranose (4l).

S32
1-O-methyl-2,3-O-isopropylidene-5-[4-(tetrahydro-2H-pyran)methyl)-1H-1,2,3-triazole-1-
yl]-β-D-ribofuranose (4m).

1-O-methyl-2,3-O-isopropylidene-5-[4-(1-hydroxy-1,3-dimethylbutyl)-1H-1,2,3-triazole-1-
yl]-β-D-ribofuranose (4n).

S33
1,2:3,4-di-O-isopropylidene-6-(4-phenyl-1H-1,2,3-triazole-1-yl)-α-D-galactopyranose. (5a).

1,2:5,6-di-O-isopropylidene-3-(4-phenyl-1H-1,2,3-triazole-1-yl)-α-D-alofuranose (6a).

S34
 α-D-xilofuranose
5-deoxy-1,2-O-isopropylidene-5-(4-phenyl-1H-1,2,3-triazole-1-yl)-α (7a).

α-D-
5-deoxy-1,2-O-isopropylidene-5-[4-(1-cyclohexene)-1H-1,2,3-triazole-1-yl]-α
xilofuranose (7b).

S35
 α-D-
5-deoxy-1,2-O-isopropylidene-5-(4-hydroxymethyl-1H-1,2,3-triazole-1-yl)-α
xilofuranose (7c).

References

(1) Verhart, C. G. J.; Carls, B. M. G.; Zwanenburg, B.; Chittenden, G. J. F. Acetalation

studies. Reaction of sucrose and some related sugars with acetone in the presence of
iodine - a novel cleavage isopropylidenation method. Recl. Trav. Chim. Pay. B.
1992, 111, 348-352.

(2) Fleetwood, A.; Hughes, N. A. Convenient synthesis of 2,3-O-isopropylidene-5-thio-

D-ribose and 5-thio- D-ribose; synthesis of 1,4-anhydro-2,3-O-isopropylidene-α- D-
ribopyranose and 1,4-anhydro-2,3-O-isopropylidene-5-thio-α- D-ribopyranose.

Carbohyd. Res. 1999, 317, 204-209.

(3) Lerner, L. M. Enantiomeric forms of 9-(5-deoxy-β-erythro-pent-4-enofuranosyl)

adenine and a new preparation of 5-deoxy-D-lyxose. Carbohyd. Res. 1977, 53, 177-
185.

S36
(4) Hill, S.; Hough, L.; Richardson, A. C. Nucleophilic replacement reactions of
sulphonates. Part I. the preparation of derivatives of 4,6-diamino-4,6-dideoxy-d-
glucose and D-galactose. Carbohyd. Res. 1968, 8, 17-18.

(5) Raymond, A. L.; Schröeder, E. F. Synthesis of some iodo-sugar derivatives. J. Am.

Chem. Soc. 1948, 70, 2785-2791.

(6) Fisher, E. Ueber die Verbindungen der Zucker mit den alkoholen und ketonen.
Chem. Ber., 1895, 28, 1145-1167.

(7) Sowa, W.; Thomas, G. H. S. Oxidation of 1,2-5,6-di-O-isopropylidene-D-glucose by

dimethyl sulfoxide-acetic anhydride. Can. J. Chem. 1966, 44, 836-838.

(8) Mancuso, A. J.; Huang, S. L.; Swern, D. Oxidation of long-chain and related
alcohols to carbonyls by dimethyl-sulfoxide activated by oxalyl chloride. J. Org.
Chem. 1978, 43, 2480-2482.

(9) Levene, P. A.; Raymond, A. L. Derivatives of monoacetone xylose. J. Biol. Chem.

1933, 102, 317-330.

(10) Baker, B. R.; Schaub, R. E. Puromycin. Synthetic Studies. XIII. Synthesis of 6-

dimethylamino-9(3’-amino-3’-deoxy-β-D-arabinofuranosyl)-purine. J. Am. Chem.
Soc. 1955, 77, 5900-5905.

S37