Smukste and Smithrud
1
2.99 (dd, J ) 5.6 Hz, J ) 14.0 Hz, 1H), 2.84 (dd, J ) 9.6 Hz,
J ) 13.6 Hz, 1H), 1.95-1.90 (m, 2H), 1.46 (s, 18H), 1.40-1.20
(m, 4H), 1.14 (s, 18H); 13C NMR (63 MHz, CDCl3) δ 172.35,
172.14, 153.12, 151.21, 147.50, 143.20, 136.62, 133.17, 131.89,
131.09, 130.24, 129.23, 128.43, 126.74, 124.55, 123.16, 113.20,
111.82, 105.35, 105.27, 80.24, 70.03-68.36 (m), 64.30, 53.92,
53.76, 52.73, 52.06, 48.86, 37.60, 34.85, 34.68, 31.39, 30.63,
according to H NMR analysis: 1H NMR (250 MHz, CD3OD)
δ 7.52-6.80 (m, 14 H), 4.76-4.47 (m, 5H (ArCH2N, 2H; R-H
of Arg, 2H; R-H of Phe, 1H)), 4.30-3.10 (m, 30H (OCH2CH2O
of crown ether, 24H; NCH2CH2 of axle, 2H; NCH2CH2 of Arg,
4H), 2.99-2.90 (m, 2H), 2.30-2.20 (m, 2H), 2.09 (s, 6H), 1.88-
1.55 (m, 4H), 1.50-0.87 (m, 24H); 13C NMR (63 MHz, DMSO-
d6) δ 182.91, 173.00, 172.00, 167.64, 150.63, 137.72, 134.35,
131.30, 129.07, 128.10, 126.29, 124.22, 122.19, 72.00-69.00
(m), 60.13, 53.34, 48.48, 40.52, 36.70, 34.60, 34.30, 31.19, 31.01,
+
29.66, 28.31, 25.89, 22.07; TOF MS m/z calcd for C64H95N4O15
1159.6794, found 1159.6783.
+
25.14, 24.68, 22.20; TOF MS m/z calcd for C69H105N12O15
1341.7822, found 1341.7902.
P h en ylalan in e Meth yl Ester Di(am in oben zo)[24]cr own -
8 Rota xa n e (14). A 200 mg (0.167 mmol) sample of [2]-
rotaxane 13 was dissolved in 2 mL of CH2Cl2, and 0.4 mL of
TFA was added. The reaction mixture was stirred under Ar
at rt. After 2 h, TLC analysis indicated that the reaction was
complete. The solvent and TFA were removed under high
vacuum. To ensure that TFA was removed, the residue was
dissolved in CH3Cl/CH3OH (9/1) and evaporated; this proce-
dure was repeated three times. The crude material was
dissolved in CH2Cl2 and extracted with 0.1 M NaHCO3. The
organic layers were collected and dried over Na2SO4. After the
solvent was removed under high vacuum, 172 mg (96%) of [2]-
rotaxane 14 was obtained, which was pure by 1H NMR
P h en yla la n in e Met h yl E st er Di(4-ca r b oxyb u t yr yl-
a m in oben zo)[24]cr ow n -8 Rota xa n e (16). To a solution of
150 mg (0.14 mmol) of amino[2]rotaxane 14 in 3 mL of CHCl3
were added 68 mg (0.60 mmol) of glutaric anhydride and 30
µL of Et3N. The reaction mixture was stirred at rt for 2 h.
The solvent was evaporated, and the remaining oily residue
was triturated with 10 mL of Et2O to remove excess glutaric
anhydride and Et3N. The solid residue was dissolved in CH2-
Cl2/CH3OH (9/1) and extracted with 1 N HCl. The organic
phases were collected and dried over Na2SO4. Solvents were
removed in vacuo, and the product was purified via column
chromatography (SiO2, CH2Cl2/CH3OH) to give 130 mg (76%)
of [2]rotaxane 16 as an off-white wax: 1H NMR (250 MHz,
DMSO-d6) δ 9.82 (s, 2H), 8.20 (d, J ) 7.6 Hz, 2H), 7.44 (s,
2H), 7.30-7.15 (m, 8H), 7.04 (d, J ) 8.4 Hz, 2H), 6.90 (d, J )
9.1 Hz), 4.55 (s, 2H), 4.45-4.40 (m, 1H), 4.20-3.95 (m, 8H),
3.90-3.10 (m, 21H + water), 2.99 (dd, J ) 5.6 Hz, J ) 13.6
Hz, 1H), 2.84 (dd, J ) 9.2 Hz, J ) 13.6 Hz, 1H), 2.40-2.20
(m, 8H), 2.00-1.90 (m, 2H), 1.90-1.80 (m, 4H), 1.50-1.40 (m,
4H), 1.13 (s, 18H); 13C NMR (CD3CN, reference 1.32 ppm) δ
174.86, 174.39, 173.11, 172.07, 153.80, 152.28, 148.32, 144.83,
138.09, 134.06, 132.92, 130.26, 129.42, 127.77, 125.15, 124.52,
113.72, 113.38, 106.83, 71.53, 71.20, 71.02, 70.85, 69.39, 69.22,
54.63, 53.67, 52.75, 52.03, 51.40, 49.63, 38.23, 36.56, 35.50,
35.32, 34.02, 33.77, 33.60, 32.58, 32.29, 31.70, 26.68, 26.27,
1
analysis (>95%): mp 56-58 °C; H NMR (400 MHz, DMSO-
d6) δ 8.18 (d, J ) 7.6 Hz, 1H), 7.39-7.17 (m, 8H), 6.73 (d, J )
8.4 Hz, 1.2 H, 64% of the conformer mixture), 6.63 (d, J ) 8.4
Hz, 0.7 H, 36% of the conformer mixture), 6.32 (s, 1.2 H, 63%
of the conformer mixture), 6.23 (s, 0.6 H, 37% of the conformer
mixture), 6.10 (d, J ) 8.4 Hz, 1.2 H, 64% of the conformer
mixture), 6.05 (d, J ) 8.4 Hz, 0.7 H, 36% of the conformer
mixture), 4.80-4.60 (m, 4H), 4.60-4.55 (m, 2H), 4.50-4.45 (m,
1H), 4.20-3.80 (m, 8H), 3.75-3.40 (m, 15H), 3.20-2.95 (m,
3H), 2.86 (dd, J ) 9.6 Hz, J ) 13.6 Hz, 1H), 1.90-1.85 (m,
2H), 1.80-1.40 (m, 4H), 1.32-1.05 (m, 18H); 13C NMR (63
MHz, DMSO-d6) δ 172.06, 171.60, 158.77, 158.19, 150.55,
147.51, 146.54, 137.17, 131.40, 128.95, 128.14, 126.46, 125.28,
123.68, 122.70, 115.28, 113.07, 107.64, 70.13-68.31 (m), 53.43,
52.04, 51.69, 48.19, 36.71, 34.27, 33.86, 31.11, 30.94, 25.29,
26.08, 25.67, 25.50, 23.01, 21.62; TOF MS m/z calcd for
+
C
64H91N4O17 1187.6379, found 1187.6388.
+
21.78; TOF MS m/z calcd for C54H79N4O11 959.5745, found
P h en yla la n in e Di(4-ca r boxybu tyr yla m in oben zo)[24]-
959.5749.
cr ow n -8 Rota xa n e (1b). A 130 mg (0.106 mmol) sample of
[2]rotaxane 16 was dissolved in 2 mL of CH3OH, and 1 N LiOH
was added to adjust the pH to 10. The reaction mixture was
stirred at rt until the starting material was consumed as
P h en ylalan in e Meth yl Ester Di(N-acetylar gin ylam in o-
ben zo)[24]cr ow n -8 Rota xa n e (15). A 200 mg (0.203 mmol)
sample of [2]rotaxane 14, 360 mg (0.812 mmol) of BOP, and
176 mg (0.812 mmol) of Ac-Arg-OH‚HCl were dissolved in 3
mL of freshly distilled DMF. A 353 µL sample of DIEA was
added, and the reaction mixture was stirred under Ar at rt
for 24 h. DMF and excess DIEA were removed under high
vacuum, and the remaining oily residue was extracted with
CH2Cl2/CH3OH (8/2)/ H2O. The organic phases were collected
and dried over Na2SO4. The product was purified using rotary
chromatography (SiO2, CH2Cl2, CH3OH; to remove the rotax-
ane, a 1% TFA solution in CH3OH was used as eluent) to give
153 mg (56%) of [2]rotaxane 15 as a yellow oil: 1H NMR (400
MHz, CD3OD) δ 7.41-6.92 (m, 14 H), 4.71 (br s, 2H), 4.60 (m,
1H), 4.46-4.44 (m, 2H), 4.22-4.00 (m, 8H), 3.84-3.48 (m, 25
H), 3.23-3.20 (m, 1H), 3.00-2.85 (m, 1H), 2.02 (s, 6H), 2.00-
1.91 (m, 2H), 1.78-1.73 (m, 4H), 1.46-1.15 (m, 26H); 13C NMR
(63 MHz, DMSO-d6) δ 177.62, 172.05, 171.57, 170.17, 169.70,
158.53, 156.96, 150.50, 143.08, 137.17, 134.27, 132.90, 131.40,
128.94, 128.10, 126.41, 123.68, 122.66, 119.24, 111.56, 104.69,
70.06-68.05 (m), 53.42, 53.06, 52.03, 51.65, 51.48, 48.16, 36.69,
34.27, 33.92, 30.90, 29.20, 28.20, 25.20, 22.33, 21.79; TOF MS
1
determined by TLC and H NMR analysis. After the solvents
were removed under high vacuum, the crude product was
dissolved in CH3OH to precipitate LiCl, which was removed
by filtration. [2]Rotaxane 1b was obtained as a yellow oil in a
greater than 95% yield, according to 1H NMR analysis: 1H
NMR (250 MHz, CD3OD) δ 7.88-6.88 (m, 14H), 4.70 (s, 2H),
4.61-4.60 (m, ∼ /2H), 4.45-4.44 (m, ∼ /2H), 4.19-4.13 (m, 8H),
4.00-3.40 (m, 20H), 3.24-3.22 (m, 2H), 3.14-3.07 (m, 1H),
2.97-2.92 (m, 2H), 2.43-2.34 (m, 6H), 2.26 (t, J ) 8.1 Hz, 2H),
1.98-1.93 (m, 6H), 1.60-1.20 (m, 4H), 1.20 (s, 18H); 13C NMR
(63 MHz, CD3OD, reference 49.0 ppm) δ 181.86, 175.21, 174.82,
174.23, 173.50, 173.38, 152.41, 148.61, 145.34, 139.63, 138.27,
134.27, 134.13, 133.13, 130.56, 130.18, 129.46, 129.08, 127.86,
127.27, 125.43, 124.36, 118.19, 113.86, 107.09, 71.83, 71.40,
71.22, 69.68, 69.45, 53.85, 52.08, 38.37, 37.91, 36.81, 36.22,
35.70, 34.02, 31.87, 27.06, 24.07, 23.64, 22.08; TOF MS m/z
1
1
+
calcd for C63H89N4O17 1173.6223, found 1173.6243.
Ack n ow led gm en t is made to the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for partial support of this re-
search. Thanks are also due to the University of
Cincinnati for partial funding. I.S. was supported by the
University of Cincinnati Research Council Fellowship
and the Stecker Fellowship.
+
m/z calcd for C70H107N12O15 1355.7980, found 1355.8617.
P h en yla la n in e Di(N-a cet yla r gin yla m in ob en zo)[24]-
cr ow n -8 Rota xa n e (1a ). A 100 mg (0.068 mmol) sample of
rotaxane 15‚3HCl was dissolved in ca. 3 mL of THF, and 1 N
LiOH was added until the pH was adjusted to 10. The reaction
mixture was stirred at rt for 12 h, at which time the starting
material was consumed according to TLC analysis (SiO2, CH2-
Cl2, CH3OH). After the solvents were removed under high
vacuum, the crude product was dissolved in CH3OH to
precipitate LiCl, which was removed by filtration. [2]Rotaxane
1a was obtained as a yellow oil in a greater than 95% yield,
Su p p or tin g In for m a tion Ava ila ble: NOESY spectrum
and assignment table of [2]rotaxane 1a . This material is
J O026530Q
2558 J . Org. Chem., Vol. 68, No. 7, 2003