P. R. Sridhar, K. R. Prabhu, S. Chandrasekaran
FULL PAPER
δ ϭ 77.0 ppm. Mass spectra were recorded with a Shimadzu
GCMS-QP5050 mass spectrometer.
CDCl3): δ ϭ 2.01 (s, 3 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.09 (s, 3 H),
2.68 (t, J ϭ 6.9 Hz, 2 H), 2.83Ϫ3.04 (m, 2 H), 3.69 (s, 3 H),
3.72Ϫ3.74 (m, 1 H), 4.14 (dd, J ϭ 2.1, J ϭ 12.3 Hz, 1 H), 4.23 (dd,
J ϭ 4.8, J ϭ 12.6 Hz, 1 H), 4.54 (d, J ϭ 9.9 Hz, 1 H), 5.02 (t, J ϭ
9.3 Hz, 1 H), 5.08 (t, J ϭ 9.3 Hz, 1 H), 5.22 (t, J ϭ 9.3 Hz, 1 H)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 20.5, 20.6, 25.3, 35.2, 51.8,
62.1, 68.3, 69.7, 73.7, 75.9, 83.9, 169.3, 169.4, 170.1, 170.6, 172.0
Bis(2,3,4,6-tetra-O-acetyl-β-D
-glucopyranosyl) Disulfide (5):[20]
Benzyltriethylammonium tetrathiomolybdate (1, 0.89 g, 1.47
mmol) was added to a solution of 2,3,4,6-tetra-O-acetyl-α-d-gluco-
pyranosyl bromide (4, 0.55 g, 1.34 mmol) in CH3CN (6 mL), and
the reaction mixture was stirred at 0 °C for 24 h. Most of the
solvent was evaporated under reduced pressure, and the black ma-
terial was extracted with CH2Cl2/Et2O (1:4, 15 mL ϫ 3). It was
then filtered through a pad of Celite, and the same extraction was
repeated four times. The combined filtrates, on removal of solvent,
yielded the crude product, which on recrystallisation (ether/petro-
leum ether, 9:1) afforded the disulfide 5 (0.462 g, 95%) as a white
solid (m.p. 140Ϫ142 °C (ref.[20] 142Ϫ143 °C). IR (neat): ν˜ ϭ 1720,
ppm. Low-resolution MS: calcd. m/z 450 [Mϩ], found 473 [Mϩ
ϩ
Na]. C18H26O11S (450.5): calcd. C 47.99, H 5.82; found C 48.36,
H 5.88.
Phenyl 2-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosylthio)ethyl Sul-
fone (9): [α]2D5 ϭ Ϫ33 (c ϭ 1, chloroform). IR (neat): ν˜ ϭ 1227,
1
1633, 1748, 2946 cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 2.00 (s,
3 H), 2.02 (s, 3 H), 2.03 (s, 3 H), 2.13 (s, 3 H), 2.80Ϫ2.90 (m, 1
H), 2.95Ϫ3.05 (m, 1 H), 3.38Ϫ3.48 (m, 2 H), 3.67Ϫ3.71 (m, 1 H),
4.10Ϫ4.16 (m, 2 H), 4.48 (d, J ϭ 9.9 Hz, 1 H), 4.89 (t, J ϭ 9 Hz,
1 H), 5.00 (t, J ϭ 9.6 Hz, 1 H), 5.19 (t, J ϭ 8.4 Hz, 1 H), 7.61(t,
J ϭ 6.9 Hz, 2 H), 7.69 (d, J ϭ 6.9 Hz,1 H), 7.93 (d, J ϭ 8.1 Hz, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 20.3, 20.4, 20.5, 20.6,
23.0, 56.9, 61.8, 67.9, 69.2, 73.3, 75.9, 86.5, 128.0, 129.4, 134.0,
138.4, 169.2, 169.3, 169.9, 170.6 ppm. Low-resolution MS: calcd.
m/z 532 [Mϩ], found 533 [Mϩ ϩ 1]. C22H28O11S2 (532.6): calcd. C
49.61, H 5.30; found C 49.83, H 5.22.
1
2852, 2923 cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 2.00 (s, 6 H),
2.03 (s, 6 H), 2.10 (s, 6 H), 2.13 (s, 6 H), 3.81 (td, J5,6eq ϭ 1.8,
J4,5 ϭ 9.9 Hz, 2 H), 4.28 (pair of dd, J5,6eq ϭ 1.8, J5,6ax ϭ 4.2,
J
6ax,6eq ϭ 12.5 Hz, 4 H), 4.9 (d, J1,2 ϭ 9.4 Hz, 2 H), 5.02Ϫ5.36 (m,
6 H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 20.1, 61.2, 67.4, 69.2,
73.4, 75.6, 86.6, 168.9, 169.5, 170.2 ppm. Low-resolution MS:
calcd: m/z 726 [Mϩ], found 727 [Mϩ ϩ 1]. C28H38O18S2 (726.7):
calcd. C 46.28, H 5.23; found C 45.95, H 5.25.
Typical Experimental Procedure for the One-Pot Tandem Sulfur
Transfer/Reduction/Michael Addition: Tetrathiomolybdate
1
N-Acetyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylthio)-DL-
(0.609 g, 1 mmol) was added in one portion to a well-stirred solu-
tion of sugar bromide (1 mmol) in CH3CN (10 mL), and the reac-
tion mixture was stirred at 28 °C for 2 h. The reaction was moni-
tored by TLC. Once the starting material had disappeared (30 min),
tetrathiomolybdate 1 (0.609 g, 1 mmol) was once again added, fol-
lowed by addition of the Michael acceptor (1 mmol) and the reac-
tion mixture was stirred under argon at room temperature for 3 h.
The solvent was removed under vacuum. The black residue was
extracted with diethyl ether/dichloromethane mixture (4:1, 25 mL
ϫ 4) and filtered through a Celite pad. The filtrate was concen-
trated under vacuum and the crude product was purified by flash
column chromatography on silica gel.
cysteine Methyl Ester (10): 1H NMR (300 MHz, CDCl3): δ ϭ
1.95Ϫ2.06 (m, 15 H), 2.94Ϫ3.03 (m, 1 H), 3.10Ϫ3.18 (m, 1 H),
3.70 (s, 3 H), 3.95Ϫ4.15 (m, 3 H), 4.84 (t, J ϭ 9.6 Hz, 1 H),
4.72Ϫ4.78 (m, 1 H), 4.89Ϫ5.01(m, 2 H), 5.16 (dt, J ϭ 2.7, J ϭ
9.3 Hz, 1 H), 6.55 (d, J ϭ 7.2 Hz, 1 H), 6.62 (d, J ϭ 7.2 Hz, 1 H)
ppm. 13C NMR (75 MHz, CDCl3): 14.1, 20.4, 20.5, 20.9, 22.7, 31.5,
32.2, 51.7, 52.2, 52.5, 52.6, 60.3, 61.7, 62.0, 67.9, 68.0, 69.6, 69.7,
73.4, 75.8, 76.0, 83.1, 83.5, 169.2, 169.3, 169.4, 169.8, 169.9, 170.5,
170.6, 170.8 ppm. Low-resolution MS: calcd. m/z 507 [Mϩ], found
530 [Mϩ ϩ Na]. High-resolution MS: calcd. for C20H29NO12S ϩ
Na 530.1409; found 530.1414.
Methyl 3-(6-Deoxy-α-D-glucopyranos-6-ylthio)propionate (14): Am-
4-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosylthio)butan-2-one (6):
monium tetrathiomolybdate (2, 0.262 g, 1 mmol) was added to a
solution of methyl 6-bromo-6-deoxy-α-d-glucopyranoside (12,
0.256 g, 1 mmol) in water (6 mL), and the reaction mixture was
stirred for 4 h. The reaction was monitored by TLC. Once the start-
ing material had disappeared (3 h), ammonium tetrathiomolybdate
(2, 0.262 g, 1 mmol) was once again added, followed by methyl
acrylate (0.086 g, 1 mmol), and the reaction mixture was stirred at
room temperature for a further 3 h. The solvent was removed under
vacuum. The black residue was extracted with methanol (10 ϫ
3 mL) and filtered through a Celite pad. The combined filtrates
were concentrated under vacuum and the crude product was puri-
fied by flash column chromatography on silica gel (eluent: meth-
anol/chloroform, 1:9) to yield compound 14 (0.243 g, 82%) as a
IR (neat): ν˜ ϭ 1748, 2940 cmϪ1. 1H NMR (300 MHz, CDCl3): δ ϭ
2.01 (s, 3 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.09 (s, 3 H), 2.17 (s, 3
H), 2.75Ϫ2.98 (m, 4 H), 3.67Ϫ3.73 (m, 1 H), 4.15 (dd, J ϭ 2.1,
J ϭ 12.3 Hz, 1 H), 4.23 (dd, J ϭ 4.8, J ϭ 12.3 Hz, 1 H), 4.52 (d,
J ϭ 9.9 Hz, 1 H), 5.20 (t, J ϭ 9.6 Hz, 1 H), 5.08 (t, J ϭ 9.9 Hz, 1
H), 5.22 (t, J ϭ 9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
20.5, 20.6, 20.7, 23.8, 30.0, 44.1, 62.0, 68.2, 69.7, 73.8, 75.9, 83.9,
169.4, 169.4, 170.1, 170.6, 206.4 ppm. Low-resolution MS: calcd:
m/z 434 [Mϩ], found 435 [Mϩ ϩ 1]. C18H26O10S (434.5): calcd. C
49.76, H 6.03; found C 49.41, H 5.78.
3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosylthio)propionitrile (7):
[α]2D5 ϭ Ϫ32 (c ϭ 1, chloroform). IR (neat): ν˜ ϭ 1752, 2250, 2853,
1
1
2925 cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 1.98 (s, 3 H), 2.00
colorless, gummy solid. H NMR (300 MHz, CDCl3): δ ϭ 2.65 (t,
J ϭ 7.2 Hz, 2 H), 2.71Ϫ2.76 (m, 1 H), 2.88 (t, J ϭ 7.2 Hz, 2 H),
3.10 (m, 1 H), 3.36 (t, J ϭ 9 Hz, 1 H), 3.44 (s, 3 H), 3.53 (dd, J ϭ
3.3, J ϭ 9.6 Hz, 1 H), 3.70 (m, 5 H), 4.73 (d, J ϭ 3.3 Hz, 1 H)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 28.1, 33.7, 34.6, 51.8, 55.2,
71.6, 72.0, 72.7, 74.1, 99.2, 172.6 ppm. Low-resolution MS: calcd.
m/z 296 [Mϩ], found 297 [Mϩ ϩ 1]. High-resolution MS: calcd. for
C11H20O7S ϩ Na 319.0828; found 319.0822.
(s, 3 H), 2.03 (s, 3 H), 2.07 (s, 3 H), 2.63Ϫ2.77 (m, 2 H), 2.86Ϫ2.88
(m, 1 H), 2.96Ϫ3.05 (m, 1 H), 3.69Ϫ3.74 (m, 1 H), 4.16 (dd, J ϭ
2.1, J ϭ 12.3 Hz, 1 H), 4.20 (dd, J ϭ 4.8, J ϭ 12.3 Hz, 1 H), 4.55
(d, J ϭ 10.2 Hz, 1 H), 5.00 (t, J ϭ 9.3 Hz, 1 H), 5.04 (t, J ϭ
10.2 Hz, 1 H), 5.20 (t, J ϭ 9.3 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 19.6, 20.5, 20.6, 20.7, 25.7, 61.9, 68.0, 69.4, 73.5, 76.1,
83.3, 118.0, 169.3, 169.4, 170.0, 170.5 ppm. Low-resolution MS:
calcd. m/z 417 [Mϩ], found 418 [Mϩ ϩ 1]. C17H23NO9S (417.4):
calcd. C 48.91, H 5.55; found C 49.26, H 5.65.
α,β-Unsaturated δ-Lactone 16:[24] 2,3-Di-O-acetyl-6-O-tosyl-d-glu-
cal (15, 0.3 g, 0.78 mmol) was placed in a 50-mL round-bottomed
Methyl 3-(2,3,4,6-Tetra-O-acetyl-β-
D
-glucopyranosylthio)propionate flask and cooled to Ϫ20 °C with the aid of an ice/sodium chloride
(8): IR (neat): ν˜ ϭ 1750, 2852, 2923 cmϪ1
.
1H NMR (300 MHz,
mixture. m-Chloroperbenzoic acid (0.163 g, 0.93 mmol) was dis-
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Eur. J. Org. Chem. 2004, 4809Ϫ4815