PAPER
N-Glycosyl Amides as Glycosyl Donors
129
Isopropyl 2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyranoside (14)
According to the general glycosylation procedure, glycoside 14 was
synthesized with anhyd i-PrOH (1 mL) as a colorless crystalline sol-
id; yield: 119 mg, (69%); mp 98 °C; [a]D25 –4.7 (c = 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.08, 1.13, 1.15, 1.23 (4 × s, 36 H,
CH3, Piv), 1.10 (d, J = 5.6 Hz, 3 H, H-2¢), 1.20 (d, J = 5.6 Hz, 3 H,
H-2¢¢), 3.89 (sep, J = 5.9 Hz, 1 H, H-1¢), 3.98 (m, 2 H, H-6a/b), 4.14
(m, 1 H, H-5), 4.54 (d, J = 7.7 Hz, 1 H, H-1), 5.06 (dd, J = 10.7, 3.3
Hz, 1 H, H-3), 5.16 (dd, J = 10.7, 7.7 Hz, 1 H, H-2), 5.36 (d, J = 3.3
Hz, 1 H, H-4).
13C NMR (75 MHz, CDCl3): d = 22.0, 23.3 [OCH(CH3)2], 26.3,
27.05, 27.09, 27.2 [C(CH3)3, Piv], 38.69, 38.72, 39.1 [C(CH3)3,
Piv], 61.5 (C-6), 67.0, 68.9, 70.9, 72.7 (C-2–C-5), 71.2
[OCH(CH3)2], 100.1 (C-1), 176.6, 177.0, 177.3, 177.9 (CO, Piv).
identified by 1H NMR spectroscopy;10,20 yield: 124 mg (78%);
[a]D25 +8.2 (c = 1, CHCl3), {Lit.10 [a]D25 +8.2 (c = 2, CHCl3)}.
N-(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyranosyl)allylamine
(17)
Compound 17 was prepared according to the general glycosylation
procedure with anhyd allylamine (1.0 mL) as a colorless oil; yield:
74 mg (43%); [a]22 D +12.3 (c = 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.08, 1.13, 1.15, 1.23 (4 × s, 36 H,
CH3, Piv), 1.73 (br s, 1 H, NH), 3.25 (dd, J = 14.6, 6.3 Hz, 1 H, H-
1¢a), 3.46 (dd, J = 14.6, 5.4 Hz, 1 H, H-1¢b), 3.86–4.13 (m, 3 H, H-5,
H-6a/b), 4.06 (d, J = 8.8 Hz, 1 H, H-1), 4.97–5.06 (m, 3 H, H-2, H-
3¢a/b), 5.14 (dd, J = 10.3, 3.4 Hz, 1 H, H-3), 5.37 (d, J = 2.9 Hz, 1 H,
H-4), 5.66–5.82 (m, 1 H, H-2¢).
13C NMR (75 MHz, CDCl3): d = 27.1, 27.2 [C(CH3)3, Piv], 38.7,
39.1 [C(CH3)3, Piv], 47.8 (C-1¢), 61.6 (C-6), 67.4, 68.6, 71.4, 71.6
(C-2–C-5), 88.9 (C-1), 115.7 (C-3¢), 136.4 (C-2¢), 176.9, 177.2,
177.7, 177.9 (CO, Piv).
Anal. Calcd for C29H50O10: C, 62.34; H, 9.02. Found: C, 62.34; H,
9.00.
Cyclohexyl 2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyranoside
(15)
According to the general glycosylation procedure, glycoside 15 was
prepared from anhyd cyclohexanol (1 mL) as a colorless crystalline
solid; yield: 154 mg, (83%); mp 112 °C; [a]D25 +5.7 (c = 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.08, 1.13, 1.15, 1.23 (4 × s, 36 H,
CH3, Piv), 1.58 (m, 10 H, Hcyclohexyl), 3.53 (m, 1 H, H-1cyclohexyl), 3.96
(m, 2 H, H-6a/b), 4.13 (m, 1 H, H-5), 4.58 (d, J = 7.7 Hz, 1 H, H-1),
5.06 (dd, J = 10.3, 3.3 Hz, 1 H, H-3), 5.16 (dd, J = 10.7, 7.7 Hz, 1
H, H-2), 5.36 (d, J = 3.3 Hz, 1 H, H-4).
13C NMR (75 MHz, CDCl3): d = 24.1, 25.5 (CH2, cyclohexyl),
27.05, 27.08, 27.1, 27.2 [C(CH3)3, Piv], 31.7, 31.95, 33.5 (CH2, cy-
clohexyl), 38.67, 38.70, 39.0 [C(CH3)3, Piv], 61.5 (C-6), 67.0, 68.9,
70.9, 71.2 (C-2–C-5), 78.4 (CH, cyclohexyl), 99.9 (C-1), 176.5,
177.0, 177.4, 177.9 (CO, Piv).
Anal. Calcd for C29H49NO10: C, 62.88; H, 8.89; N, 2.52. Found: C,
62.58; H, 9.04; N, 2.53.
N-(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyranosyl)piperidine
(18)
According to the general glycosylation procedure, compound 18
was prepared from anhyd piperidine (1 mL) as a colorless oil; yield:
133 mg, (74%); [a]D25 –3.7 (c = 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.08, 1.13, 1.15, 1.22 (4 × s, 36 H,
CH, Piv), 1.39 (m, 6 H,), 2.52 (m, 2 H, H-1¢), 2.90 (m, 2 H, H-1¢¢),
3.89 (m, 2 H, H-6), 3.92 (d, J = 7.4 Hz, 1 H, H-1), 4.10 (m, 1 H, H-
5), 5.08 (dd, J = 10.3, 3.3 Hz, 1 H, H-3), 5.36 (m, 2 H, H-2, H-4).
13C NMR (75 MHz, CDCl3): d = 24.7, 26.3, 27.9 (CH2, piperidine),
27.02, 27.05, 27.1 [C(CH3)3, Piv], 38.6, 38.7, 39.0 [C(CH3)3, Piv],
49.0 (CH2, piperidine), 61.4 (C-6), 64.9, 67.3, 71.7, 72.0 (C-2–C-5),
94.7 (C-1), 176.8, 176.9, 177.2, 177.9 (CO, Piv).
HRMS: m/z calcd for C32H54O10Na: 621.37; found: 621.35.
Cholesteryl 2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyranoside
(16)
Anal. Calcd for C31H53NO9: C, 63.78; H, 9.15; N, 2.40. Found: C,
63.80; H, 9.13, N, 2.38.
According to the general glycosylation procedure, glycoside 16 was
synthesized from cholesterol (357 mg, 0.92 mmol) as a colorless
crystalline solid; yield: 183 mg, (66%); mp 192 °C; [a]D25 –6.3 (c =
1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 0.64 (s, 3 H, H-18), 0.82 (d, J =
1.1 Hz, 3 H, H-26), 0.85 (d, J = 1.5 Hz, 3 H, H-27), 0.88 (d, J = 6.6
Hz, 3 H, H-21), 0.94 (s, 3 H, H-19), 1.09, 1.15, 1.24 (3 × s, 36 H,
CH3, Piv), 1.20–1.60 (m, 21 H, CH, CH2, chol), 1.77–1.82 (m, 2 H,
CH, CH2, chol), 1.96–2.00 (m, 3 H, CH, CH2, chol), 2.22 (d, J = 7.7
Hz, 2 H, H-4), 3.43–3.46 (m, 1 H, H-3), 3.96 (m, 2 H, H-6(a/b)-Gal),
4.14 (m, 1 H, H-5Gal), 4.58 (d, J = 7.7 Hz, 1 H, H-1Gal), 5.07 (dd,
J = 10.3, 3.3 Hz, 1 H, H-3Gal), 5.17 (dd, J = 10.7, 7.7 Hz, 1 H, H-
Glycosylation Reactions with N-(2,3,4,6-Tetra-O-acetyl-b-D-ga-
lactopyranosyl)anisamide 20; General Procedure
To a solution of N-(2,3,4,6-tetra-O-acetyl-b-D-galactopyrano-
syl)anisamide (20; 200 mg, 0.42 mmol) and PPh3 (218 mg, 0.83
mmol) in anhyd CH3CN (15 mL) a solution of CBr4 (413 mg, 1.25
mmol) in anhyd CH3CN (5 mL) was added at r.t. under Ar atmo-
sphere. After stirring at r.t. for 4 h, the reaction mixture was cooled
to –40 °C, and a solution of the glycosyl acceptor (amounts given
for each compound) and AgOTf (213 mg, 0.83 mmol) in anhyd
CH3CN (5 mL) was added. While slowly warming up to r.t., the
mixture was stirred for a period of 6–16 h and then filtered for re-
moval of AgBr. Anhyd CH2Cl2 (100 mL) was added, and the solu-
tion was washed with sat aq NaCl (3 × 50 mL). The organic layer
was dried over MgSO4. The solvent was evaporated under reduced
pressure and the resulting residue was purified by flash chromatog-
raphy (cyclohexane–EtOAc) to afford b-configured O- and N-gly-
cosides.
2Gal), 5.30 (d, J = 4.4 Hz, 1 H, H-6), 5.37 (d, J = 2.6 Hz, 1 H, H-4Gal).
13C NMR (75 MHz, CDCl3): d = 11.8, 18.4, 19.3, 22.9 (CH, CH3,
chol), 23.8, 24.3, 26.9 (CH2, chol), 27.06, 27.14, 27.2 [C(CH3)3,
Piv], 28.0 (CH, CH3, chol), 28.2, 29.6 (CH2, chol), 31.9 (CH, CH3,
chol), 31.9 (CH2, chol), 35.8 (CH, CH3, chol), 36.2 (CH2, chol),
36.8 (Cq, chol), 37.2 (CH2, chol), 38.67, 38.72, 39.0 [C(CH3)3, Piv],
38.9, 39.5, 39.7 (CH2, chol), 42.3 (Cq, chol), 50.1, 56.1, 56.7 (CH2,
chol), 61.4 (C-6Gal), 66.9, 68.9, 70.9, 71.1 (C-2Gal–C-5Gal), 80.0 (C-
1, chol), 100.1 (C-1Gal), 122.1 (C-6, chol), 140.3 (C-5, chol), 176.6,
177.0, 177.3, 177.9 (CO, Piv).
Benzyl 2,3,4,6-Tetra-O-acetyl-b-D-galactopyranoside (21)
According to the general glycosylation procedure, compound 21
was prepared from anhyd benzyl alcohol (1 mL) as a colorless oil;
yield: 71 mg, (39%); [a]D25 –27.1 (c = 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.95, 1.98, 2.04, 2.13 (4 × s, 12 H,
CH3, Ac), 3.86 (t, J = 6.2 Hz, 1 H, H-5), 4.10–4.23 (m, 2 H, H-6a/b),
4.49 (d, J = 8.1 Hz, 1 H, H-1), 4.61 (d, J = 12.1 Hz, 1 H, H-1¢a), 4.88
(d, J = 12.5 Hz, 1 H, H-1¢b), 4.96 (dd, J = 10.3, 2.9 Hz, 1 H, H-3),
5.25 (dd, J = 10.3, 8.1 Hz, 1 H, H-2), 5.36 (d, J = 2.6 Hz, 1 H, H-4),
7.26–7.31 (m, 5 H, HAr).
HRMS: m/z calcd for C53H88O10Na: 907.63; found: 907.62.
N-(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyranosyl)amine (1)
According to the general glycosylation procedure, glycosylamine 1
was synthesized with concd. aq NH3 (1 mL) as a colorless solid and
Synthesis 2005, No. 1, 122–130 © Thieme Stuttgart · New York