PAPER
Facile Synthesis of Armed and Disarmed Colitose Thioglycosides
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Ethyl 1-Thio-b-L-fucopyranoside (6)
Ethyl 2,3-Di-O-acetyl-1-thio-b-L-fucopyranoside
a-L-Fucose (1) (30.00 g, 0.183 mol) and DMAP (2.235 g, 0.018
mol) were dissolved in pyridine (600 mL) and the mixture was
cooled to 0 °C. Ice cold Ac2O (300 mL) was added with stirring over
a period of 30 min and stirring was continued at 0 °C for 1 h. The
reaction mixture was concentrated, and a solution of the residue in
toluene (1000 mL) was washed with 1 M aq HCl (3 × 300 mL), H2O
(300 mL) and brine (300 mL). The organic phase was dried, concen-
trated, and toluene (3 × 200 mL) was evaporated from the residue to
give the crude peracetate (59.813 g, 98%), containing 2 as the main
component (c.f. text above).
1H NMR: d = 5.26 (t, J = 9.9 Hz, 1 H, H2), 4.98 (dd, J = 3.0, 9.9 Hz,
1 H, H3), 4.43 (d, J = 10.2 Hz, 1 H, H1), 3.90 (br s, 1 H, H4), 3.74
(dq, J = 0.8, 6.6 Hz, 1 H, H5), 2.76 (dq, J = 7.4, 12.5 Hz, 1 H, SCH),
2.69 (dq, J = 7.4, 12.5 Hz, 1 H, SCH¢), 2.10 (s, 3 H, COCH3), 2.06
(s, 3 H, COCH3), 1.34 (d, J = 6.3 Hz, 3 H, H6), 1.27 (t, J = 7.4 Hz,
3 H, SCH2CH3).
Ethyl 2,4-Di-O-acetyl-1-thio-b-L-fucopyranoside (4)
1H NMR: d = 5.21 (dd, J = 0.8, 3.7 Hz, 1 H, H4), 5.01 (t, J = 9.8 Hz,
1 H, H2), 4.41 (d, J = 9.9 Hz, 1 H, H1), 3.82 (m, 1 H, H3), 3.78 (dq,
J = 1.1, 6.3 Hz, 1 H, H5), 2.76 (br s, 1 H, OH), 2.75 (dq, J = 7.4,
12.6 Hz, 1 H, SCH), 2.69 (dq, J = 7.4, 12.6 Hz, 1 H, SCH¢), 2.19 (s,
3 H, COCH3), 2.13 (s, 3 H, COCH3), 1.28 (t, J = 7.4 Hz, 3 H,
SCH2CH3), 1.21 (d, J = 6.6 Hz, 3 H, H6).
HBr in HOAc (120 mL) was added at 0 °C to a solution of the fore-
going peracetate in CH2Cl2 (120 mL). The cooling was removed
and, after 1 h, the reaction mixture was concentrated. Toluene (4 ×
100 mL) was evaporated from the residue to give 5 as a viscous yel-
low oil.
13C NMR: d = 171.3 (COCH3), 170.9 (COCH3), 83.1 (C1), 73.4
(C5), 73.1 (C4), 72.3 (C3), 70.9 (C2), 24.1 (SCH2), 21.0 (COCH3),
20.8 (COCH3), 16.6 (C6), 14.7 (SCH2CH3).
EtSH (40.5 mL, 0.540 mol) was added slowly at 0 °C to a mechan-
ically stirred suspension of NaH (10.8 g, 0.270 mol) in DME (400
mL). After 30 min, a solution of the crude bromide 5 in DME (200
mL) was added to the thick white slurry. The ice bath was removed
and stirring was continued at r.t. After 3 h, when TLC indicated dis-
appearance of the bromide, MeOH (600 mL) followed by anhyd
K2CO3 (6.219 g, 0.045 mol) were added and the mixture was stirred
overnight. The mixture was neutralized with IR-120(H+) ion ex-
change resin (ca 180 g), the resin was filtered off, washed with
MeOH, the filtrate was concentrated, and chromatography
(CH2Cl2–MeOH, 95:5) of the residue afforded 6 (30.414 g, 81%,
based on crude peracetate). An analytical sample of 6 was prepared
MS (FAB+): m/z = 231 [M+ – SEt], 233 [M+ – OAc], 293 [M+ + H].
Anal. Calcd for C12H20O6S: C, 49.30; H, 6.90. Found: C, 49.29; H,
6.85.
Ethyl 2,4-Di-O-acetyl-3-O-(imidazol-1-ylthiocarbonyl)-1-thio-
b-L-fucopyranoside (9)
1,1¢-Thiocarbonyldiimidazole (TCDI, 26.780 g, 0.150 mol) and
DMAP (0.765 g, 6.261 mmol) were added at r.t. to a stirred solution
of 4 (36.606 g, 0.125 mol) in DMF (500 mL). After 3 h, the mixture
was concentrated and the residue was chromatographed (n-hexane–
EtOAc, 3:2) to give 9 (48.453 g, 96%). An analytical sample of 9
was prepared by crystallization (twice) from isopropyl ether; mp
79.0–79.5 °C; [a]D25 –21.8°.
1H NMR: d = 8.24 (t, J = 0.9 Hz, 1 H, NCHN), 7.51 (t, J = 1.5 Hz,
1 H, CSNCHCH), 7.02 (dd, J = 0.9, 1.8 Hz, 1 H, CSNCHCH), 5.72
(dd, J = 3.6, 9.9 Hz, 1 H, H3), 5.61 (dd, J = 0.8, 3.6 Hz, 1 H, H4),
5.49 (t, J = 9.9 Hz, 1 H, H2), 4.59 (d, J = 9.9 Hz, 1 H, H1), 3.93 (dq,
J = 0.8, 6.3 Hz, 1 H, H5), 2.82 (dq, J = 7.4, 12.4 Hz, 1 H, SCH), 2.76
(dq, J = 7.4, 12.4 Hz, 1 H, SCH¢), 2.15 (s, 3 H, COCH3), 2.05 (s, 3
H, COCH3), 1.31 (t, J = 7.4 Hz, 3 H, SCH2CH3), 1.27 (d, J = 6.6 Hz,
3 H, H6).
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by crystallization (twice) from Et2O; mp 83.5–84.5 °C; [a]D
+42.4°.
1H NMR: d = 4.75 (br d, J = 4.7 Hz, 1 H, OH3), 4.38 (d, J = 9.4 Hz,
1 H, H1), 4.22 (br d, J = 3.0 Hz, 1 H, OH2), 3.81 (m, 2 H, H-4,
OH4), 3.69 (dq, J = 2.6, 9.3 Hz, 1 H, H5), 3.65 (m, 2 H, H-2, H3),
2.68 (dq, J = 7.7, 12.8 Hz, 1 H, SCH), 2.66 (dq, J = 7.2, 12.8 Hz, 1
H, SCH¢), 1.25 (m, 6 H, H6, SCH2CH3).
13C NMR: d = 85.7 (C1), 75.2 (C3), 74.7 (C2), 71.8 (C4), 70.0 (C5),
24.6 (SCH2), 16.6 (C6), 15.1 (SCH2CH3).
MS (FAB+): m/z = 207 [M+ – 1], 209 [M+ + 1], 231 [M+ + 23].
Anal. Calcd for C8H16O4S: C, 46.13; H, 7.74. Found: C, 45.98; H,
7.74.
13C NMR: d = 182.6 (OCSIm), 170.1 (COCH3), 169.6 (COCH3),
137.0 (NCHN), 131.2 (CSNCHCH), 117.6 (CSNCHCH), 83.1
(C1), 80.6 (C3), 73.1 (C5), 69.4 (C4), 67.0 (C2), 24.1 (SCH2), 20.8
(COCH3), 20.4 (COCH3), 16.4 (C6), 14.7 (SCH2CH3).
Ethyl 2,4-Di-O-acetyl-1-thio-b-L-fucopyranoside (4)
CH3C(OEt)3 (40.2 mL, 0.219 mol) and CSA (1.696 g, 7.301 mmol)
were added to a stirred solution of 6 (30.414 g, 0.146 mol) in
CH2Cl2 (292 mL). After 1 h, the mixture was cooled (0 °C) and py-
ridine (292 mL), DMAP (0.892 g, 7.301 mmol) and Ac2O (68.6 mL,
0.730 mol) were added. The ice bath was removed and stirring was
continued at r.t. After 1.5 h, the mixture was diluted with CH2Cl2
(500 mL) and slowly poured into sat. aq NaHCO3 (500 mL). The
layers were separated, the aqueous phase was washed with CH2Cl2
(2 × 500 mL), and the combined organic layers were dried and con-
centrated. Toluene (3 × 200 mL) was evaporated from the residue,
and a solution of the product in 80% aq HOAc (292 mL) was stirred
at r.t. for 3 h. Concentration with co-evaporation of toluene (3 × 100
mL) gave crude 4 as a slightly yellow solid. Crystallization from
i-PrOH furnished ethyl 2,4-di-O-acetyl-1-thio-b-L-fucopyranoside
(4) as white, fluffy needles (33.160 g, two crops, 78%). The mother
liquor was chromatographed (n-hexane–EtOAc, 3:2), to give first a
small amount of ethyl 2,3-di-O-acetyl-1-thio-b-L-fucopyranoside.
Further elution gave additional 4 (3.522 g, 8%; total yield 86%). An
analytical sample of 4 was prepared by crystallization (twice) from
i-PrOH; mp 120.5–121.5 °C; [a]D25 +5.6°.
MS (CI): m/z = 341 [M+ – SEt], 403 [M+ + 1].
Anal. Calcd for C16H22O6N2S2: C, 47.75; H, 5.51; N, 6.96. Found:
C, 47.96; H, 5.52; N, 6.91.
Ethyl 2,4-Di-O-acetyl-3,6-dideoxy-1-thio-b-L-xylo-hexopyrano-
side (10)
A solution of 9 (2.289 g, 5.687 mmol) and AIBN (93 mg, 0.569
mmol) in toluene (23 mL) was added dropwise to a refluxing solu-
tion of Bu3SnH (3.01 mL, 11.374 mmol) in toluene (46 mL). After
3 h, the reaction mixture was concentrated, and a solution of the res-
idue in n-hexane (100 mL) was extracted with CH3CN (3 × 100
mL). The combined CH3CN phases were concentrated and the res-
idue was chromatographed (n-hexane–EtOAc, 5:1) to give 10 as a
colorless oil (1.451 g, 92%), which solidified upon standing. An an-
alytical sample of 10 was prepared by crystallization (twice) from
n-hexane–EtOAc; mp 76.5–77.0 °C; [a]D25 +66.9°.
1H NMR: d = 5.02 (m, 2 H, H2, H4), 4.48 (d, J = 9.9 Hz, 1 H, H1),
3.74 (dq, J = 1.4, 6.3 Hz, 1 H, H5), 2.75 (dq, J = 7.4, 12.5 Hz, 1 H,
SCH), 2.69 (dq, J = 7.4, 12.5 Hz, 1 H, SCH¢), 2.36 (ddd, J = 3.2, 5.0,
14.0 Hz, 1 H, H3eq), 2.14 (s, 3 H, COCH3), 2.07 (s, 3 H, COCH3),
Synthesis 2004, No. 15, 2505–2508 © Thieme Stuttgart · New York