Functionalization of Cyclodextrins
alloepoxide 5 (500 mg, 0.45 mmol), benzylmercaptan (300 µL,
2.5 mmol), and Cs2CO3 (730 mg, 2.2 mmol) were added to DMF
(5 mL) and the resultant mixture was stirred at 80 °C. After
6 h, the reaction mixture was added to water (40 mL) and
extracted with diethyl ether to remove the excess thiol. The
aqueous solution was evaporated to dryness and the residue
was applied to reversed-phase chromatography (Lobar column,
Size C). Elution of the column with a gradient from 10% CH3-
OH (0.5 L) to 20% methanol (0.5 L) followed by a second
gradient from 20% CH3OH (1 L) to 40% methanol-H2O (500
mL) afforded 21 (eluted faster, 208 mg, 37%) and 22 (eluted
slower, 293 mg, 53%) as colorless solids.
Data for 21: Rf 0.17 (solvent A). 13C NMR (125 MHz, DMSO-
d6, TMS int.) δ 138.0, 129.2, 128.2, 126.8, 102.5, 102.1, 102.0,
101.8, 101.7, 101.3, 101.0, 81.9, 81.8, 81.3, 81.2, 80.5, 77.0, 78.5,
74.2, 74.2, 73.1, 73.0, 72.9, 72.6, 72.4, 72.3, 72.2, 72.1, 72.0,
71.9, 71.4, 68.9, 60.9, 60.2, 60.0, 59.9, 59.8, 59.7, 47.3, 34.8.
1H NMR (500 MHz, DMSO-d6, TMS int., deuterated) δ 7.41-
3A-Am in o-3A-d eoxy-â-cyclod extr in (26). General proce-
dure B was used starting with 24 to give amine 26 (96%) as a
colorless solid. Rf 0.39 (solvent D). 13C NMR (125 MHz, DMSO-
d6, TMS int.) δ 102.0, 101.8, 101.2, 81.5, 81.4, 81.0 (4), 80.2,
73.0, 73.2, 72.9, 72.6, 72.5, 72.2, 72.1, 71.9, 60.0, 59.8, 55.3.
1H NMR (500 MHz, DMSO-d6, TMS int., deuterated) δ 4.87-
4.82 (m, 7H), 3.71-3.55 (m, 27H), 3.40-3.23 (m, 14H), 2.79
3
(t, J ) ∼9.8 Hz, 1H). FAB-MS m/z 1134 (M + H), 1156 (M +
Na).
2A-Deoxy-2A-iod o-a ltr o-â-cyclod ext r in (27) a n d 3A-
Deoxy-3A-iod o-â-cyclod extr in (28). â-CD alloepoxide 5 (160
mg, 0.14 mmol), lithium iodide dihydrate (570 mg, 3.4 mmol),
and trimethylammonium chloride (202 mg, 2.1 mmol) were
dissolved in DMF (3.2 mL) and the resultant solution was
stirred at 80 °C for 1 d. After diluted with water (5 mL), the
reaction mixture was desalted on an electrolytic desalting
system and chromatographed on a reversed-phase Lobar
column (Size B). Elution of the column with water (100 mL)
followed by a gradient elution from water (500 mL) to 40%
methanol (500 mL) afforded 27 (eluted faster, 49 mg, 27%)
and 28 (eluted slower, 102 mg, 57%) as colorless solids.
Data for 27: Rf 0.2 (solvent A). 13C NMR (100 MHz, D6O,
CH3CN int.) δ 102.9, 101.4, 101.3, 100.9, 100.8, 100.7, 100.3,
80.8, 80.4, 80.3, 80.0, 79.0, 77.4, 78.0, 74.3, 73.1, 73.0, 72.9,
72.8, 72.6, 72.4, 72.3, 71.9, 71.7, 71.6, 71.3, 70.5, 69.9, 60.3,
3
3
7.24 (m, 5H), 5.03 (d, J ) 6.8 Hz, 1H), 4.90 (d, J ) 3.6 Hz,
3
3
1H), 4.87 (d, J ) 3.7 Hz, 1H), 4.84-4.79 (m, 4H), 4.02 (d, J
3
3
) 12.6 Hz, 1H), 3.88 (d, J ) 12.6 Hz, 1H), 3.82 (dd, J ) 5.8,
-5.1 Hz, 1H), 3.75-3.49 (m, 28H), 3.44-3.26 (m, 12H), 2.87
3
(dd, J ) ∼10.5, 6.8 Hz, 1H). FAB-MS m/z 1241 (M + H).
Data for 22: Rf 0.17 (solvent A). 13C NMR (125 MHz, DMSO-
d6, TMS int.) δ 137.3, 129.3, 128.3, 126.9, 102.0, 101.9, 101.8,
101.7, 101.0, 100.8, 81.8, 81.5, 81.3, 81.1, 76.0, 73.7, 73.3, 73.1,
73.0, 72.9, 72.5, 72.4, 72.3, 72.1, 72.0, 71.9, 60.1, 60.0, 59.8,
50.5, 35.0. 1H NMR (500 MHz, DMSO-d6, TMS int., deuter-
ated) δ 7.39-7.24 (m, 5H), 4.91-4.83 (m, 7H), 3.98 (d, 3J )
1
60.1, 59.9, 59.7, 59.5, 30.3. H NMR (400 MHz, D6O, CH3CN
int.) δ 4.99 (d, 3J ) 7.0 Hz, 1H), 4.81-4.68 (m, 6H), 3.94-3.88
(m, 2H), 3.72-3.40 (m, 28H), 3.32-3.20 (m, 12H). FAB-MS
m/z 1245 (M + H), (neg) m/z 1243 (M - H).
Data for 28: Rf 0.2 (solvent A). 13C NMR (100 MHz, D2O,
CH3CN int.) δ 101.5, 101.2, 100.2, 80.8, 80.7, 80.3, 80.1, 73.6,
72.8, 72.6, 72.4, 72.1, 71.9, 71.8, 71.7, 71.5, 70.5, 71.3, 60.3,
3
12.0 Hz, 1H), 3.91 (d, J ) 12.0 Hz, 1H), 3.72-3.47 (m, 29H),
3
3.45-3.23 (m, 12H), 2.85 (t, J ) 10.6 Hz, 1H). FAB-MS m/z
1241 (M + H).
1
60.0, 59.8, 36.3. H NMR (400 MHz, D2O, CH3CN int.) δ 5.01
2A-Azid o-2A-d eoxy-a ltr o-â-cyclod extr in (23) a n d 3A-
Azid o-3A-d eoxy-â-cyclod extr in (24). General procedure A
was used starting with â-CD alloepoxide 5 to give 23 (eluted
faster, 25%) and 24 (eluted slower, 65%).
3
3
(d, J ) 3.7 Hz, 1H), 4.91 (d, J ) 3.7 Hz, 1H), 3.90-3.84 (m,
4H), 4.78 (d, 3J ) 3.7 Hz, 1H), 4.13 (t, 3J ≈ 10.4 Hz, 1H), 3.81-
3.63 (m, 29H), 3.44-3.34 (m, 12H). FAB-MS m/z 1267 (M +
Na).
An alternative procedure in DMF afforded the two products
in a quite different ratio. Alloepoxide 5 (1.0 g, 0.9 mmol) and
NaN3 (580 mg, 8.9 mmol) were added to DMF (20 mL) and
the mixture was stirred at 95 °C for 18 h. After being diluted
with water (500 mL) and filtered, the clear solution was
chromatographed on a reversed-phase Lobar column (Size C).
Elution of the column with a gradient from H2O (1 L) to 40%
methanol (1 L) afforded 23 and 24 in 6.7% and 82% yields,
respectively.
Data for 23: Rf 0.48 (solvent C). 13C NMR (125 MHz, D2O,
CH3CN int.) δ 102.2, 102.3, 102.1, 101.7, 101.4, 101.1, 81.5,
81.1, 80.7, 79.5, 78.9, 76.3, 73.8, 73.6, 73.4, 73.2, 72.5, 72.4,
72.3, 72.2, 72.1, 71.9, 69.5, 64.1, 61.4, 61.0, 60.7, 60.1. 1H NMR
(500 MHz, D2O, CH3CN int.) δ 5.08 (d, 3J ) 3.8 Hz, 2H), 3.99-
3.95 (m, 4H), 4.81 (d, 3J ) 7.3 Hz, 1H), 4.24 (m, 1H), 3.96-
3.72 (m, 26H), 3.72-3.64 (m, 3H), 3.61-3.47 (m, 12H). FAB-
MS m/z 1160 (M + H), 1182 (M + Na).
Data for 24: Rf 0.48 (solvent C). 13C NMR (125 MHz, D2O,
CH3CN int.) δ 102.6, 102.4, 101.3, 101.6, 81.9, 81.7, 81.6, 78.9,
73.9, 73.8, 73.4, 73.0, 72.9, 72.7, 72.5, 72.3, 66.6, 61.3, 61.2,
61.1. 1H NMR (500 MHz, D2O, CH3CN int.) δ 4.99 (m, 7H),
3.90-3.74 (m, 28H), 3.63 (dd, 3J ) 10.3, 3.6 Hz, 1H), 3.56-
3.48 (m, 12H), 3.44 (t, 3J ) 9.3 Hz, 1H). FAB-MS m/z 1160 (M
+ H), 1182 (M + Na).
3A,3C-Dia zid o-3A,3C-d id eoxy-â-cyclod extr in (32). Gen-
eral procedure A was used starting with â-CD AC-dialloepoxide
6 to give diazide 32 (eluted last, 34%) as a colorless solid. 13C
NMR (125 MHz, DMSO-d6, TMS int.) δ 101.7, 101.5, 101.4,
100.4, 100.2, 81.4, 81.0, 80.8, 80.4, 77.5, 77.4, 72.8, 72.7, 72.3,
72.1, 71.9, 71.8, 71.7, 71.6, 71.4, 66.4, 66.3, 59.9, 59.8, 59.7,
1
59.5. H NMR (500 MHz, DMSO-d6, TMS int., deuterated) δ
3
4.89 (d, J ) 3.1 Hz, 2H), 4.85 (m, 5H), 3.75-3.54 (m, 28H),
3.47-3.28 (m, 14H). FAB-MS m/z 1185 (M + H), 1207 (M +
Na).
3A,3D-Dia zid o-3A,3D-d id eoxy-â-cyclod extr in (33). Gen-
eral procedure A was used starting with â-CD AD-diallo-
epoxide 7 to give diazide 33 (eluted last, 30%) as a colorless
solid. 13C NMR (125 MHz, DMSO-d6, TMS int.) δ 101.7, 101.5,
101.4, 100.4, 100.2, 81.2, 81.0, 80.9, 80.8, 80.4, 77.4, 72.8, 72.3,
72.2, 71.9, 71.7, 71.6, 71.5, 71.4, 66.6, 66.5, 60.0, 59.9, 59.7,
59.6, 59.5. 1H NMR (500 MHz, DMSO-d6, TMS int., deuter-
ated) δ 4.89-4.85 (m, 7H), 3.71-3.54 (m, 28H), 3.48-3.28 (m,
14H). FAB-MS m/z 1185 (M + H), 1207 (M + Na).
3A,3C,3E-Tr ia zid o-3A,3C,3E-tr id eoxy-â-cyclod extr in (34).
General procedure A was used starting with 8 to give triazide
34 (28%) as a colorless solid. 13C NMR (125 MHz, DMSO-d6,
TMS int.) δ 101.4, 100.3, 81.0, 80.6, 77.5, 77.3, 72.7, 72.3, 72.2,
72.0, 71.9, 71.7, 66.6, 66.5, 66.3, 59.9, 59.8, 59.6. 1H NMR (500
MHz, DMSO-d6, TMS int., deuterated) δ 4.91-4.85 (m, 7H),
3.86-3.52 (m, 28H), 3.47-3.28 (m, 14H). FAB-MS m/z 1210
(M + H), 1232 (M + Na).
2A-Am in o-2A-d eoxy-a ltr o-â-cyclod ext r in (25). General
procedure B was used starting with 23 to give amine 25 (89%)
as a colorless solid. Rf 0.39 (solvent D). 13C NMR (75 MHz,
D2O, CH3CN int.) δ 105.3, 102.6, 102.5, 102.2, 101.9, 81.8, 81.6,
81.5, 81.3, 80.6, 79.6, 76.9, 73.9, 73.7, 73.6, 73.3, 72.9, 72.8,
72.6, 72.5, 72.4, 72.3, 72.1, 71.0, 61.1, 60.4, 54.7. 1H NMR (500
MHz, D2O, CH3CN int.) δ 5.07-4.95 (m, 6H), 4.69 (d, 3J ) 7.5
Hz, 1H), 4.18 (ddd, 3J ) ca. 7.2, ca. 3.8, ca. 3.8 Hz, 1H), 3.92-
3A,3C-Dia m in o-3A,3C-d id eoxy-â-cyclod extr in (35). Gen-
eral procedure B was used starting with 32 to give diamine
35 (91%) as a colorless solid. Rf 0.15 (solvent D). 13C NMR (125
MHz, DMSO-d6, TMS int.) δ 102.0, 101.8, 100.2, 100.1, 81.4,
81.1, 80.9, 80.2, 73.2, 72.8, 72.7, 72.6, 72.2, 71.9, 60.1, 59.8,
55.4, 55.3. 1H NMR (500 MHz, DMSO-d6, TMS int., deuter-
ated) δ 4.86-4.82 (m, 7H), 3.72-3.54 (m, 26H), 3.40-3.21 (m,
3
3.66 (m, 27H), 3.63 (dd, J ) 10.5, 4.0 Hz, 1H), 3.60-3.47 (m,
3
12H), 2.99 (dd, J ) 10.5, 7.5 Hz, 1H). FAB-MS m/z 1134 (M
3
+ H), 1156 (M + Na).
14H), 2.78 (t, J ) ∼9.8 Hz, 2H). FAB-MS m/z 1133 (M + H).
J . Org. Chem, Vol. 68, No. 24, 2003 9465