Studies Directed to the Synthesis of Oligochitosans
FULL PAPER
3β-Cholestanyl 2-(Allyloxycarbonylamino)-3,6-di-O-benzoyl-2-deoxy- 3β-Cholestanyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(2,2,2-trichloroethyl-
β-D-glucopyranoside (21): Thioglycoside 16 (62 mg, 0.11 mmol), 3β- oxycarbonylamino)-β-
D
-glucopyranoside (24):[32] Thioglycoside 6
cholestanol (50 mg, 0.13 mmol), N-iodosuccinimide (31 mg,
0.14 mmol in 0.40 mL CH3CN), and trimethylsilyl triflate (10 µL,
0.06 mmol) in CH2Cl2 (3.0 mL) reacted for 10 min at –20 °C. Col-
umn chromatography (EtOAc/pentane, 1:2) yielded 83 mg (93%) of
glucosaminide 21 as colorless oil. 1H NMR (CDCl3, T = 60 °C,
400 MHz): δ = 8.05 (t, J = 8.0 Hz, 4 H, Ar-H), 7.57 (t, J = 7.6 Hz,
1 H, Ar-H), 7.56 (t, J = 7.6 Hz, 1 H, Ar-H), 7.44 (t, J = 7.6 Hz, 2
H, Ar-H), 7.42 (t, J = 8.0 Hz, 2 H, Ar-H), 5.78 (ddt, J = 5.6, 10.8,
(90 mg, 0.15 mmol), 3β-cholestanol (66 mg, 0.17 mmol), N-iodos-
uccinimide (40 mg, 0.18 mmol), and trimethylsilyl triflate (20 µL,
0.11 mmol) in CH2Cl2 (2.0 mL) reacted at 0 °C for 20 min. Column
chromatography (EtOAc–pentane 1:4) gave 24 (125 mg, 96%) as a
white powder. 1H NMR (CDCl3, 400 MHz): δ = 5.38 (t, J =
10.0 Hz, 1 H, 3-H), 5.12 (d, J = 8.0 Hz, 1 H, NH), 5.04 (t, J =
10.0 Hz, 1 H, 4-H), 4.81 (d, J = 8.4 Hz, 1 H, 1-H), 4.71 (ABspin,
J = 12.0 Hz, 2 H, CH2), 4.27 (dd, J = 4.8, 12.4 Hz, 1 H, 6-H), 4.10
17.6 Hz, 1 H, CH=CH2), 5.39 (m, 1 H, 3-H), 5.18 (d, J = 17.8 Hz, (dd, J = 2.0, 12.4 Hz, 1 H, 6Ј-H), 3.69 (m, 1 H, 5-H), 3.57 (tt, J =
1 H, CH=CH2), 5.06 (d, J = 10.8 Hz, 1 H, CH=CH2), 4.85 (d, J
= 8.8 Hz, 1 H, 1-H), 4.78 (d, J = 8.0 Hz, 1 H, NH), 4.67 (ABspin,
J = 9.6 Hz, 2 H, CH2), 4.47 (m, 2 H, 6-H & 6Ј-H), 3.81–3.74 (m,
2 H, 4-H & 5-H), 3.69 (q, J = 8.8 Hz, 1 H, 2-H), 3.59 (sept, J =
5.2, 11.2 Hz, 1 H, Chol-3-H), 3.48 (dt, J = 8.4, 10.0 Hz, 1 H, 2-H),
2.07 (s, 3 H, COCH3), 2.03 (s, 3 H, COCH3), 2.02 (s, 3 H, COCH3),
2.00–0.54 (m, 40 H, Chol-H), 0.76 (s, 3 H, Chol-CH3), 0.63 (s, 3H
Chol-CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 170.9, 170.7,
5.2 Hz, 1 H, Chol-3-H), 3.10 (br. s, 1 H, OH), 2.10–0.50 (m, 31 H, 169.7, 154.0, 109.9, 79.7, 77.6, 71.8, 69.1, 62.4, 56.8, 56.6, 56.5,
Chol-H), 0.92 (d, J = 6.4 Hz, 3 H, Chol-CH3), 0.88 (d, J = 6.8 Hz,
6 H, 2 Chol-CH3), 0.77 (s, 3 H, Chol-CH3), 0.66 (s, 3 H, Chol-
CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.6, 167.0, 156.0,
133.6, 133.3, 132.8, 130.2 (2 C), 130.0 (2 C), 129.9, 129.4, 128.6 (2
C), 128.5 (2 C), 117.6, 99.8, 79.6, 76.4, 74.1, 70.3, 65.8, 64.1, 56.7,
56.5, 54.5, 44.9, 42.8, 40.2, 39.7, 37.1, 36.3, 35.9, 35.7, 35.6, 34.7,
32.2, 29.5, 28.9, 28.4, 28.2, 24.4, 24.0, 23.0, 22.7, 21.4, 18.8, 12.4,
12.2 ppm. HR-MS (ES-TOF) calcd. for C51H71NO9 [M + Na+]
864.5027, found 864.5018.
54.5, 53.0, 44.9, 42.8, 40.2, 39.8, 37.1, 36.3, 35.9, 35.7, 35.6, 34.6,
32.2, 29.4, 29.0, 28.4, 28.2, 24.4, 24.0, 23.0, 22.7, 21.4, 20.8 (3 C),
18.8, 12.4, 12.2 ppm.
3β-Cholestanyl 3,4,6-Tri-O-acetyl-2-(allyloxycarbonylamino)-2-de-
oxy-β-D-glucopyranoside (25): Thioglycoside 8 (90 mg, 0.18 mmol),
3β-cholestanol (92 mg, 0.24 mmol), N-iodosuccinimide (56 mg,
0.24 mmol in 0.40 mL CH2Cl2), and trimethylsilyl triflate (20 µL,
0.11 mmol) in CH2Cl2 (3 mL) reacted for 5 min at 0 °C. Column
chromatography (EtOAc/CH2Cl2, 14:86) yielded 25 (131.9 mg,
95%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ = 5.90 (ddt,
J = 6.0, 10.4, 17.2 Hz, 1 H, CH=CH2), 5.32 (dd, J = 9.2, 10.8 Hz,
1 H, 3-H), 5.29 (d, J = 17.2 Hz, 1 H, CH=CH2), 5.19 (d, J =
10.4 Hz, 1 H, CH=CH2), 5.00 (t, J = 9.6 Hz, 1 H, 4-H), 4.75 (d, J
= 8.0 Hz, 1 H, 1-H), 4.66 (d, J = 7.6 Hz, 1 H, NH), 4.56 (m, 2 H,
Alloc-CH2), 4.25 (dd, J = 5.2, 12.0 Hz, 1 H, 6-H), 4.13 (dd, J =
2.4, 12.0 Hz, 1 H, 6Ј-H), 3.68 (m, 1 H, 5-H), 3.57 (tt, J = 5.6,
11.2 Hz, 1 H, Chol-3-H), 3.46 (dt, J = 8.0, 9.2 Hz, 1 H, 2-H), 2.07
(s, 3 H, COCH3), 2.05 (s, 3 H, COCH3), 2.04 (s, 3 H, COCH3),
2.00–0.57 (m, 46 H, Chol-H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 167.6, 167.0, 156.0, 133.6, 133.3, 132.8, 130.2 (2 C), 130.0 (2
C), 129.9, 129.4, 128.6 (2 C), 128.5 (2 C), 117.6, 99.8, 79.6, 76.4,
1-Hexyl 3,6-Di-O-Benzoyl-2-deoxy-2-phthalimido-β-D-glucopyrano-
side (22): Thioglycoside 17 (21 mg, 34 µmol), 1-hexanol (4.8 µL,
38 µmol), N-iodosuccinimide (9 mg, 40 µmol in 0.15 mL CH3CN),
and trimethylsilyl triflate (4.0 µL, 22 µmol) in CH2Cl2 (1.5 mL) re-
acted at 0 °C for 90 min. Column chromatography (EtOAc/CH2Cl2,
1
1:12) gave 22 in 83% yield (17 mg) as a colorless syrup. H NMR
(CDCl3, 400 MHz): δ = 8.11 (d, J = 7.6 Hz, 2 H, Phth-H), 7.90 (d,
J = 7.6 Hz, 2 H, Phth-H), 7.80 (m, 2 H, Ar-H), 7.69–7.66 (m, 2 H,
Ar-H), 7.60 (t, J = 7.6 Hz, 1 H, Ar-H), 7.50 (t, J = 7.2 Hz, 1 H,
Ar-H), 7.48 (t, J = 7.6 Hz, 2 H, Ar-H), 7.35 (t, J = 7.6 Hz, 2 H,
Ar-H), 5.92 (dd, J = 8.4, 10.4 Hz, 1 H, 3-H), 5.44 (d, J = 8.4 Hz,
1 H, 1-H), 4.79 (dd, J = 4.4, 12.0 Hz, 1 H, 6-H), 4.68 (dd, J = 2.0,
12.0 Hz, 1 H, 6Ј-H), 4.46 (dd, J = 8.4, 10.4 Hz, 1 H, 4-H), 3.96– 74.1, 70.3, 65.8, 64.1, 56.7, 56.5, 54.5, 44.9, 42.8, 40.2, 38.7, 37.1,
3.89 (m, 2 H, 2-H & 5-H), 3.85 (dt, J = 6.4, 9.6 Hz, 1 H, Hex-1- 36.3, 35.9, 35.7, 35.6, 34.7, 32.2, 29.5, 28.9, 28.4, 28.2, 24.4, 24.0,
H), 3.47 (dt, J = 6.4, 9.6 Hz, 1 H, Hex-1Ј-H), 3.42 (br. s, 1 H, OH), 23.0 (2 C), 22.7, 21.4, 18.8, 12.4, 12.2 ppm. HR-MS (ES-TOF)
1.50–1.34 (m, 2 H, Hex-CH2), 1.12–0.92 (m, 6 H, 3ϫ Hex-CH2),
0.68 (t, J = 7.2 Hz, 3 H, Hex-CH3) ppm. 13C NMR (CDCl3,
100 MHz): δ = 167.3, 167.1, 134.3 (2 C), 133.7, 133.4, 131.6 (2 C),
130.09 (2 C), 130.06 (2 C), 129.9, 129.0, 128.6 (2 C), 123.7 (2 C),
98.5, 74.6, 74.5, 70.7, 70.3, 63.8, 54.7, 31.4, 29.4, 25.6, 22.6, 14.0
ppm. HR-MS (ES-TOF) calcd. for C34H35NO9 [M + Na+]
624.2210, found 624.2205.
calcd. for C51H71NO9 [M + Na+] 841.5129, found 841.5124.
p-Methylphenyl 4-O-(3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-
glucopyranosyl)-3,6-di-O-benzoyl-2-deoxy-2-phthalimido-1-thio-β-
D
-
-
D
glucopyranoside (26): Thioglycoside 9 (104 mg, 0.22 mmol), 1-ben-
zenesulfinyl piperidine (50 mg, 0.24 mmol), 2,6-di-tert-butyl-4-
methylpyridine (89 mg, 0.43 mmol), and 4-Å mol. sieves in dry
CH2Cl2 (1.5 mL) was stirred under argon for 30 min. The mixture
was cooled to –78 °C and trifluoromethanesulfonic anhydride
(48 µL, 0.29 mmol) was added. After 30 min, a –78 °C cold solu-
tion of 17 (203 mg, 0.33 mmol) in dry CH2Cl2 (0.5 mL) was added
dropwise. After 15 min stirring at –78 °C, triethylamine (0.2 mL)
was added and the mixture was warmed to room temperature, di-
1-Hexyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(2,2,2-trichloroethyloxycar-
bonylamino)-β-D-glucopyranoside (23):[31] Thioglycoside 6 (92 mg,
0.16 mmol), freshly distilled 1-hexanol (22 µL, 0.18 mmol), N-iodo-
succinimide (43 mg, 0.19 mmol) and trimethylsilyl triflate (20 µL,
11 mmol) in CH2Cl2 (2.0 mL) reacted at 0 °C for 10 min. Column
chromatography (EtAOc/CH2Cl2, 1:9) yielded 23 (86 mg, 97%) as luted with CH2Cl2 (15 mL) and filtered. The organic phase was
a colorless foam. 1H NMR (CDCl3, 400 MHz): δ = 5.32 (t, J =
10.0 Hz, 1 H, 3-H), 5.07 (t, J = 10.0 Hz, 1 H, 4-H), 5.05 (d, J =
9.2 Hz, 1 H, 1-H), 4.71 (ABspin, J = 12.0 Hz, 2 H, CH2CCl3), 4.64
(d, J = 8.0 Hz, 1 H, NH), 4.28 (dd, J = 4.8, 12.0 Hz, 1 H, 6-H),
4.13 (dd, J = 2.4, 12.0 Hz, 1 H, 6Ј-H), 3.87 (dt, J = 6.8, 9.6 Hz, 1
washed with saturated aqueous NaHCO3 (1ϫ15 mL), and brine
(1ϫ15 mL), dried with Na2SO4, and the solvents evaporated to
dryness. The product was purified by column chromatography
(EtOAc/CH2Cl2, 1:9) to give 26 (140 mg, 62%) as a colorless foam.
1H NMR (CDCl3, 400 MHz): δ = 7.91–7.39 (m, 18 H, Ar-H), 7.15
H, Hex-1-H), 3.69 (m, 1 H, 5-H), 3.59 (dt, J = 8.4, 10.0 Hz, 1 H, (d, J = 8.0 Hz, 2 H, Ar-H), 6.77 (d, J = 8.0 Hz, 2 H, Ar-H), 6.11
2-H), 3.48 (dt, J = 6.8, 9.6 Hz, 1 H, Hex-1Ј-H), 2.09 (s, 3 H, (dd, J = 8.8, 10.0 Hz, 1 H, 3-H), 5.67 (d, J = 10.8 Hz, 1 H, 1-H),
COCH3), 2.03 (s, 6 H, 2ϫ COCH3), 1.62–1.52 (m, 2 H, Hex-CH2), 5.61 (d, J = 8.4 Hz, 1 H, 1-H), 5.54 (dd, J = 9.2, 10.8 Hz, 1 H, 3-
1.35–1.24 (m, 6 H, 3ϫ Hex-CH2), 0.88 (t, J = 7.2 Hz, 3 H, Hex- H), 4.96 (t, J = 10.0 Hz, 1 H, 4-H), 4.68 (dd, J = 2.0, 12.0 Hz, 1
CH3) ppm.
H, 6-H), 4.27 (t, J = 10.0 Hz, 1 H, 2-H), 4.22 (dd, J = 8.4, 10.4 Hz,
Eur. J. Org. Chem. 2007, 3392–3401
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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