M. Sollogoub, P. Sinay» et al.
FULL PAPER
De-O-benzylation of cyclohexyl 2,3,4,6-tetra-O-benzyl-a-d-glucopyrano-
side (29): DIBAL-H (2.3 mL, 3.45 mmol) was added to a solution of 29
(107 mg, 172 mmol) in toluene (4.6 mL) in the general procedure for de-
O-alkylation, and the system was stirred for 5 h at 508C. After purifica-
tion by silica gel chromatography (Cy/EtOAc 4:1), cyclohexyl 3,4,6-tri-O-
benzyl-a-d-glucopyranoside (31, 35 mg, 39%) and cyclohexyl 2,3,4-tri-O-
benzyl-a-d-glucopyranoside (30, 39 mg, 42%) were obtained.
De-O-benzylation of 6A,6D-butyl-capped a-cyclodextrin (33): DIBAL-H
(2 mL, 3.5 mmol) was added dropwise to a solution of 33 (250 mg,
101 mmol) in toluene (1mL), and the system was stirred at 50 8C for 2 h
by the general procedure for de-O-alkylation. After purification by silica
gel chromatography (Cy/EtOAc 2:1), 34 (200 mg, 86%) was obtained as
a white foam.
Compound 34: [a]D20
=
+ 22 (CHCl3, c = 1.0); 1H NMR (400 MHz,
Compound 30: [a]D20
(CHCl3, c = 0.57)]; H NMR (400 MHz, CDCl3): d = 1.18 1.49 (m, 6H;
= +60 (CHCl3, c = = +60
1.0) [lit.[48] [a]D20
À
À
À
À
CDCl3): D = 1.36 1.49 (m, 2H; O CH2 CH2 ), 1.55 1.68 (m, 2H; O
1
À
À
À
À
À
CH2 CH2 ), 2.20 (brs, 2H; OH), 3.26 3.34 (m, 2H; O CH2 CH2 ),
3
3
3.36 3.45 (m, 4H; 6-H, 4-H), 3.42 (dd, J2,3 = 9.3 Hz, J2,1 = 3.2 Hz, 2H;
2-H), 3.42 3.50 (m, 2H; O CH2 CH2 ), 3.53 (dd, J2,3 = 9.2 Hz, J2,1
3.7 Hz, 2H; 2-H), 3.54 (dd, J2,3 = 9.4 Hz, J2,1 = 3.6 Hz, 2H; 2-H), 3.59
c-H, d-H, e-H), 1.71 1.79, 1.90 1.99 (2 m, 4H; b-H, f-H), 2.09 (d,
3
3
À
À
À
3JOH,2 = 9.2 Hz, 1H; OH), 3.61 3.71 (m, 1H; a-H), 3.66 (t, J4,3
= =
3J4,5
3
=
3
3
2
3
8.7 Hz, 1H; 4-H), 3.70 (dd, J6,6’ = 10.5 Hz, J6,5 = 2.0 Hz, 1H; 6-H), 3.74
2
(d, J = 10.8 Hz, 2H; 6-H), 3.86 3.96 (m, 8H; 6-H, 2î5-H, 4-H), 4.02 (t,
3
3
3
(dt, J2,3
= 8.5 Hz, 1H; 3-H), 3.81 (dd, J6’,6 = 10.5 Hz, J6’,5 = 3.8 Hz, 1H; 6’-H),
= =
3J2,OH = 9.2 Hz, J2,1 = 3.8 Hz, 1H; 2-H), 3.78 (t, J3,4 3J3,2
3J4,3
=
3J4,5 = 8.8 Hz, 2H; 4-H), 4.07 4.28 (m, 12H; 3-H, 5-H, 6-H), 4.38
2
3
(d, 2J = 12.6 Hz, 2H; CHPh), 4.41 4.54 (m, 12H; 5îCHPh, 6-H), 4.57
3
3
3
3.92 (ddd, J5,4 = 10.0 Hz, J5,6 = 3.8 Hz, J5,6’ = 2.0 Hz, 1H; 5-H), 4.52,
2
2
(d, J = 11.9 Hz, 2H; CHPh), 4.65 (d, J = 12.5 Hz, 2H; CHPh), 4.85 (d,
4.97 (AB, JAB = 10.6 Hz, 2H; CH2Ph), 4.53, 4.68 (AB, JAB = 12.1 Hz,
3J1,2 = 3.2 Hz, 2H; 1-H), 4.91 (d, 2J = 10.3 Hz, 2H; CHPh), 4.94 (d, 2J
3
2H; CH2Ph), 4.98, 5.02 (AB, JAB = 11.1 Hz, 2H; CH2Ph), 5.07 (d, J1,2
=
= 10.3 Hz, 2H; CHPh), 4.99 (d, J1,2 = 3.7 Hz, 2H; 1-H), 5.00 (d, 2J =
3
3.8 Hz, 1H; 1-H), 7.30 7.40 (m, 15H; 15îaromatic-H) ppm; 13C NMR
11.4 Hz, 4H; 2îCHPh), 5.18 (d, J1,2 = 3.6 Hz, 2H; 1-H), 5.36 (d, 2J =
3
(100 MHz, CDCl3): d = 23.9, 24.1, 25.5, 31.7, 33.4 (C-b, C-c, C-d, C-e, C-
f), 68.5 (C-6), 70.5 (C-a), 73.0 (C H), 73.5, 75.1, 75.3 (3îOCH2Ph), 76.2
10.6 Hz, 4H; 2îCHPh), 7.10 7.41 (m, 70H; aromatic-H) ppm; 13C NMR
À
À
À
À
(100 MHz, CDCl3): d = 26.5 (O CH2 CH2 ), 61.5, 69.1 (2îC-6), 70.6
(O CH2 CH2 ), 71.6, 71.7, 71.8 (3îC-5), 71.9 (O CH2Ph), 72.0 (C-6),
72.8, 72.9, 73.1, 74.6, 75.7, 76.3 (6îO CH2Ph), 78.0, 78.1, 79.5 (3îC-2),
À
À
À
(C H), 78.7 (C H), 83.8 (C H), 96.8 (C-1), 127.6 128.5 (15îCH-aro-
matic), 138.0, 138.2, 138.8 (3îC-arom. quat.) ppm; MS (DCI, NH3): m/z:
550 [M+NH3+H]+.
À
À
À
À
À
80.4, 80.6 (2îC-3), 80.8, 80.8 (2îC-4), 81.2 (C-3), 81.5 (C-4), 97.5, 99.9,
100.3 (3îC-1), 126.4 128.2 (35îCH-aromatic), 138.0 (2îC-arom. quat.),
138.1, 138.6, 139.2, 139.4, 139.6, (5îC-arom. quat.) ppm; MS (FAB): m/z:
2311.0 (100) [M+Na]+ ; elemental analysis calcd (%) for C138H150O30
(2288.6): C 72.42, H 6.61; found C 72.61, H 6.52.
6A,6D-Butyl-capped 6C,6F-di-O-methyl-a-cyclodextrin (35): NaH (60% w/w,
45 mg, 428 mmol) and MeI (60 mL, 428 mmol) were added under argon
at room temperauture to a stirred solution of 34 (490 mg, 214 mmol) in
anhydrous DMF (10 mL). After 3 h stirring, the reaction mixture was hy-
drolysed with MeOH and concentrated under vacuum. The residue was
dissolved in DCM (60 mL) and washed with aqueous saturated NH4Cl
(2î30 mL) and aqueous saturated NaCl (30 mL). The organic layer was
dried over MgSO4, filtered and concentrated under vacuum. After purifi-
cation by silica gel chromatography (Cy/EtOAc 3:1), 35 was obtained as
a white foam (488 mg, 98%).
Compound 31: [a]D20
CDCl3): d = 1.20 1.52 (m, 6H; c-H, d-H, e-H), 1.66 (brt, JOH,6
=
+61(CHCl 3, c
=
0.9); 1H NMR (400 MHz,
3
=
3JOH,6’
= 5.8 Hz, 1H; OH), 1.72 1.81, 1.86 1.97 (2 m, 4H; b-H, f-H), 3.53 (dd,
3
3
3J2,1 = 3.7 Hz, J2,3 = 9.5 Hz, 1H; 2-H), 3.57 (t, J4,3
4-H), 3.52 3.63 (m, 1H; a-H), 3.71 3.86 (m, 3H; 5-H, 6-H, 6 ’-H), 4.07 (t,
3J3,2 3J3.4 = 9.5 Hz, 1H; 3-H), 4.68, 4.93 (AB, JAB = 10.9 Hz, 2H;
=
3J4,5 = 9.5H; 1H;
=
CH2Ph), 4.70, 4.79 (AB, JAB = 11.9 Hz, 2H; CH2Ph), 4.87, 5.05 (AB,
3
JAB = 10.8 Hz, 2H; CH2Ph), 4.94 (d, J1,2 = 3.7 Hz, 1H; 1-H), 7.30 7.40
(m, 15H; 15îaromatic-H) ppm; 13C NMR (100 MHz, CDCl3): d = 24.1,
24.4, 25.6, 31.4, 33.3 (C-b, C-c, C-d, C-e, C-f), 62.0 (C-6), 70.6 (C-a), 73.0,
75.1(2îO CH2Ph), 75.5 (C H), 75.6 (OCH2Ph), 77.6 (C H), 80.1(C H),
À
À
À
À
81.9 (C H), 94.6 (C-1), 127.5 128.5 (15îC-aromatic), 138.1, 138.2, 138.9
(3îC-arom. quat.) ppm; MS (DCI, NH3): m/z: 550 [M+NH3+H]+ ; ele-
mental analysis calcd (%) for C33H40O6 (532.3): C 74.41, H 7.57; found C
74.14, H 7.86.
Compound 35: [a]D20
= +19 (CHCl3, c =
1.0); 1H NMR (400 MHz,
6A,6D-Butyl-capped a-cyclodextrin (33): PtO2 was added to a solution of
6A,6D-butylene-capped a-cyclodextrin[13] (1g, 405 mmol) in EtOAc
(30 mL). The reaction mixture was stirred under an H2 atmosphere for
3 h, filtered on a Celite pad and concentrated under vacuum. After puri-
fication by silica gel chromatography (Cy/EtOAc 6:1), 33 (965 mg, 97%)
À
À
À
À
CDCl3): d = 1.25 1.33 (m, 2H; O CH2 CH2 ), 1.60 1.70 (m, 2H; O
À
À
À
À
À
CH2 CH2 ), 3.27 3.33 (m, 2H; O CH2 CH2 ), 3.34 (s, 6H; OMe), 3.37
À
À
À
3.41(m, 2H; O CH2 CH2 ), 3.43 3.48 (m, 6H; 2-H, 4-H, 6-H), 3.51
3
3
¾
3.58 (m, 4H; 2-H, 6-H), 3.61(dd, J2,3 = 9.5 Hz, J2,1 = 3.7 Hz, 2H; 2-H),
3.66 (d, 2J = 9.8 Hz, 2H; 6-H), 3.94 4.05 (m, 8H; 2î4-H, 5-H, 6-H),
2
3
3.86 (d, J = 10.0 Hz, 2H; 6-H), 4.07 (brd, J5,4 = 9.7 Hz, 2H; 5-H), 4.12
was obtained as a white foam.
3
3
3
(dd, J3,2
9.8 Hz, 2H; 3-H), 4.28 (dd, J5,4 = 10.5 Hz, J5,6 = 7.5 Hz, 2H; 5-H), 4.36
= 9.6 Hz, J3,4 = 8.0 Hz, 2H; 3-H), 4.23 (t, J3,4 = =
3J3,2
Compound 33: [a]D20
= +34 (CHCl3, c =
1.0); 1H NMR (400 MHz,
3
3
À
À
À
À
CDCl3): d = 1.10 1.20 (m, 2H; O CH2 CH2 ), 1.45 1.55 (m, 2H; O
(d, 2J = 12.6 Hz, 2H; CHPh), 4.38 (t, J3,4
=
3J3,2 = 9.5 Hz, 2H; 3-H),
3
À
À
À
À
À
À
CH2 CH2 ), 3.04 3.10 (m, 2H; O CH2 CH2 ), 3.18 3.25 (m, 2H; O
4.42 (d, 2J = 13.0 Hz, 2H; CHPh), 4.43 (d, 2J = 13.0 Hz, 2H; CHPh),
4.52 (d, 2J = 12.1 Hz, 4H; 2îCHPh), 4.53 4.57 (m, 2H; 6’-H), 4.57 (d,
CH2 CH2 ), 3.34 (dd, 2J = 10.3 Hz, J6,5 = 7.3 Hz, 2H; 6-H), 3.37 3.43
3
À
À
3
3
(m, 4H; 2-H, 4-H), 3.48 (dd, J2,3 = 10.0 Hz, J2,1 = 3.5 Hz, 2H; 2-H),
2J = 12.5 Hz, 4H; 2îCHPh), 4.74 (d, J = 12.6 Hz, 2H; CHPh), 4.81 (d,
2
3.50 (d, 2J = 10.9 Hz, 2H; 6-H), 3.60 (dd, J2,3 = 9.8 Hz, J2,1 = 3.7 Hz,
3
3
3
3J1,2 = 3.4 Hz, 2H; 1-H), 4.85 (d, J1,2 = 3.2 Hz, 2H; 1-H), 4.91 (d, 2J =
2H; 2-H), 3.71(d, 2J = 9.8 Hz, 2H; 6-H), 3.78 (d, 2J = 10.0 Hz, 2H; 6-
10.5 Hz, 2H; CHPh), 4.98 (d, 2J = 12.1 Hz, 2H; CHPh), 5.02 (d, 2J =
3
12.2 Hz, 2H; CHPh), 5.12 (d, 2J = 10.9 Hz, 2H; CHPh), 5.33 (d, J1,2
=
3
H), 3.92 4.10 (m, 12H; 3-H, 2î4-H, 2î5-H, 6-H), 4.19 (dd, J3,2
=
3
3
3
3.7 Hz, 2H; 1-H), 5.39 (d, 2J
=
10.4 Hz, 2H; CHPh), 5.62 (d, 2J
=
9.8 Hz, J3,4 = 8.6 Hz, 2H; 3-H), 4.23 (dd, J5,4 = 10.0 Hz, J5,6 = 7.8 Hz,
2H; 5-H), 4.30 (d, 2J = 12.5 Hz, 2H; CHPh), 4.31 (t, J3,2
= =
3J3,4
3
10.9 Hz, 2H; CHPh), 7.11 7.48 (m, 70H; aromatic-H) ppm; 13C NMR
11.0 Hz, 2H; 3-H), 4.33 (d, 2J = 11.0 Hz, 2H; CHPh), 4.38 (d, 2J =
10.4 Hz, 2H; CHPh), 4.44 4.56 (m, 14H; 6îCHPh, 6-H), 4.73 (d, 2J =
À
À
À
À
(100 MHz): d = 26.8 (O CH2 CH2 ), 58.8 (OMe), 68.8 (C-6), 70.3 (O
À
À
À
CH2 CH2 ), 70.8 (C-6), 71.0, 71.3, 71.4 (3îC-5), 71.8 (O CH2Ph), 72.2
3
3
12.5 Hz, 2H; CHPh), 4.82 (d, J1,2 = 3.2 Hz, 2H; 1-H), 4.86 (d, J1,2
=
À
(C-6), 72.8, 72.9, 73.0, 74.2, 76.0, 76.5 (6îO CH2Ph), 77.5, 78.7, 79.8, (3î
3.5 Hz, 2H; 1-H), 4.86 (d, 2J = 10.4 Hz, 2H; CHPh), 4.93 (m, 4H; 2î
C-2), 80.6 (2îC-3), 81.0 (C-3), 81.2, 81.4, 82.2 (3îC-4), 98.3, 100.6, 100.7
(3îC-1), 126.1 128.3 (35îCH-aromatic), 137.9, 138.0, 138.3, 138.8, 139.3,
139.5, 139.7 (7îC-arom. quat.) ppm; MS (FAB): m/z: 2339.0 (100)
[M+Na]+ ; elemental analysis calcd (%) for C140H156O30 (2316.7): C 72.58,
H 6.70; found C 72.41, H 6.90.
2
3
CHPh), 5.07 (d, J = 10.8 Hz, 2H; CHPh), 5.33 (d, J1,2 = 3.7 Hz, 2H; 1-
H), 5.34 (d, 2J 10.6 Hz, 2H; CHPh), 5.58 (d, 2J
10.8 Hz, 2H;
CHPh), 7.08 7.36 (m, 80H; aromatic-H) ppm; 13C NMR (100 MHz,
=
=
À
À
À
À
À
CDCl3): d = 26.9 (O CH2 CH2 ), 68.8, 69.0 (2îC-6), 70.4 (O CH2
À
CH2 ), 71.0, 71.5, 71.6 (3îC-5), 71.8 (C-6), 72.3, 72.7, 73.0, 73.1, 73.2,
Preparation of peracetate 36: Pd/C (10%) and Pd black were added to a
solution of 35 (240 mg, 104 mmol) in an EtOAc/MeOH mixture (1:1,
1mL). The reaction mixture was stirred under an H 2 atmosphere for
À
74.1, 76.1, 76.5 (8(O CH2Ph), 77.7, 78.6, 79.8 (3(C-2), 81.0, 80.6, 80.8
(3(C-3), 81.1, 81.4, 82.2 (3(C-4), 98.3, 100.5, 100.6 (3(C-1), 126.1 128.3
(40(CH-aromatic), 138.0, 138.1, 138.2, 138.4, 138.8, 139.4, 139.5, 139.9
(8(C-arom. quat.) ppm; MS (FAB): m/z: 2491.0 (100) [M+Na]+ ; elemen-
tal analysis calcd (%) for C152H162O30 (2468.9): C 73.95, H 6.61; found: C
73.86, H 6.70.
48 h, filtrated through
a Celite pad, concentrated and dried under
vacuum on P2O5. Anhydrous pyridine (1mL) and DMAP (cat.) were
added slowly, under argon at 08C, to a stirred suspension of the crude
residue in Ac2O (2 mL). The reaction mixture was stirred at room tem-
2970
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2004, 10, 2960 2971