with CH2Cl2 (2 × 15 mL). The organic layers were combined and
washed with distilled water (2 × 15 mL), 10% aqueous citric acid
(15 mL), and brine (15 mL). The solvent was then removed
(Rotavap), and the orange solid was dried in vacuo for 30 min.
Compound 12b (0.53 g, 91%) was obtained as a yellow solid after
silica gel flash chromatography (10-30% EA/Hex). 1H NMR (400
MHz, CDCl3):10 δ (ppm) 7.43 (m, 2H, C12H/C16H), 7.38-7.30 (m,
3H, C13-15H), 6.93 (m, 2H, C28H/C36H), 6.56 (m, 2H, C29H/C35H),
5.56 (s, 2H, C10H), 4.62 (t, 2H, C6H), 3.54 (t, 2H, C7H), 3.44 (s,
3H, C9H), 2.45 (t, 2H, C37H), 1.60 (s, 9H, C19H), 1.53 (m, 2H,
C38H), 1.31 (s, 18H, C23H and C26H), 1.36-1.21 (m, 4H, C39H
2915, 2849, 2221, 1751, 11706, 1610, 1587, 1214, 1125. HRMS
(ESI): calcd for (C41H67N5O3 +H+) m/z 678.5317, obsd m/z
678.5313.
General Procedure for 8f-k. To a solution of 7f (0.41 g, 0.6
mmol) in DCM (50 mL) was added N-trichlorometylcarbonyl
isocyanate (0.23 g, 0.14 mL, 1.2 mmol) at 0 °C under N2
atmosphere. After being stirred for 1 h at 0 °C, the mixture was
allowed to warm to rt and was stirred for an additional 48 h. The
reaction mixture was cooled to 0 °C and carefully quenched with
dH2O (10 mL, exothermic reaction!) followed by 5% aqueous
NaHCO3 (10 mL). The product was extracted with DCM (300 mL),
and the organic layer was washed with dH2O (2 × 50 mL) and
brine (100 mL) and dried over anhydrous Na2SO4. After filtration
and evaporation of the solvent (rotovap), the residual mixture was
used in the next step without further purification.
and C40H), 0.87 (t, 3H, C41H). 13C NMR (400 MHz, CDCl3):10
δ
(ppm) 165.7 (C4), 161.3 (C1, C2, C3, C5 or C20), 160.9 (C1, C2, C3,
C5 or C20), 160.5 (C3 or C5), 156.0 (C2 or C20), 152.4 (C17), 149.3
(C21/C24), 145.8 (C27), 134.8 (C11), 131.7 (C34), 128.9 (C28/C36),
128.6 (C13/C15 or C14), 128.5 (C13/C15 or C14), 128.2 (C12/C16), 112.7
(C29/C35), 93.0 (C3 or C5), 83.8 (C22/C25), 70.1 (C10), 42.8 (C6 and
C7), 34.9 (C9 and C33), 34.8 (C34), 34.7, 31.5 (C35), 31.4 (C), 28.1
(C19), 27.8 (C23/C26), 22.5 (C36), 14.0 (C37). Positive ESI-MS: calcd
for (C42H57N6O8 + H+) m/z 788.4, obsd 788.8.
General Procedure for 1f-k. Compound 9f (0.15 g, 0.02 mmol)
was dissolved in a 4 M solution of HCl in dioxane (4 mL), and the
mixture was refluxed for 2 h. The white precipitate formed was
filtered, washed with DCM (5 × 10 mL), and dried on a filter.
Compound 1f was obtained as a white solid (0.11 g, quantitative).
1H NMR (500 MHz, DMSO-d6, 100 °C) δ (ppm):10 12.2-11.2
(HC, br s, 1H), 9.08 (HA, s, 1H), 8.34 (HB, s, 1H), 8.16 (HD, s, 1H),
4.04 (HC1′, t, J ) 7.5, 2H), 3.43 (HC1′′, dt, J1 ) J2 ) 6.5 Hz, 2H),
General Procedure for 4f-k. Benzyl alcohol (0.99 g, 0.91
mL, 8.8 mmol) was added to a stirred suspension of NaH (95%,
0.84 g, 35.8 mmol) in THF (10 mL) at rt under N2 atmosphere.
After 15 min the solution was cooled to 0 °C, then a solution of
compound 3f (4.48 g, 8.80 mmol) in THF (40 mL) was added.
The mixture was allowed to warm to rt, then it was refluxed for
24 h. The mixture was then cooled to 0 °C and carefully
quenched with saturated NH4Cl (10 mL). The solvent was
removed (Rotavap), and the residual solid was dissolved in Et2O,
washed with dH2O (100 mL) and brine (50 mL), and dried over
anhydrous Na2SO4. Filtration, evaporation of the solvent (Ro-
tovap) followed by silica gel chromatography (0-5% EA/Hex)
yielded 4f as a white solid (4 g, 79%). 1H NMR (400 MHz,
DMSO-d6) δ (ppm):10 9.82 (HC5, s, 1H), 9.03 (HNC1”, major,
t, J ) 4.2 Hz, 1H), 7.42-7.22 (HNC1′ overlapping with
HC8-HC12, 6H), 5.40 (HC6, s, 2H), 3.41, 3.28 (HC1′, dt, J )
13.2 Hz, J ) 5.6 Hz, 2H; HC1′′, dt, J ) 13.2 Hz, J ) 5.6 Hz,
2H), 1.52 (HC2′ + HC2”, m, 4H), 1.30-1.20 (HC3′-HC11′ + HC3′′-
HC11′′, m, 32H), 0.83 (HC12′ + HC12′′, t, J ) 6.8 Hz, 6H). 13C
NMR (100 MHz, CDCl3) δ (ppm):10 185.8 (C5), 171.5, 163.5,
162.3 (C1, C2, C4), 136.7 (C7), 128.5, 127.9, 127.7 (C8-12), 92.8
1.68-1.58 (HC2′ + HC2′′, m, 4H), 1.38-1.24 (HC3′-HC11′
+
HC3′′-HC11′′, m, 36H), 0.88 (HC12′ + HC12′′, t, J ) 6.5 Hz, 6H).
1H NMR (300 MHz, CDCl3, 40 °C) δ (ppm):10 12.7-12.2 (HC,
br. s, 1H), 9.35 (HA, s, 1H), 9.04, 9.01 (HB, HD, 2H), 4.13 (HC1′′,
br s, 2H), 3.50 (HC1′′, br s, 2H), 1.80-1.60 (HC2′ + HC′′, m, 4H),
1.40-1.25 (HC3′-HC11′ + HC3′′-HC11′′, m, 36H), 0.90 (HC12′
+
HC12′′, t, J ) 6.8 Hz, 6H). 1H NMR (500 MHz, CF3CO2D) δ (ppm):
10 4.50 (HC1′′, br s, 2H), 3.87 (HC1′′, br s, 2H), 2.05-1.95 (HC2′ +
HC2′′, m, 4H), 1.63-1.40 (HC3′-HC11′ + HC3′′-HC11′′, m, 36H),
1.05 (HC12′ + HC12′′, t, J ) 5.9 Hz, 6H). 13C NMR (100 MHz,
CDCl3) δ (ppm):10 165.8 (C5), 162.8 (C2), 157.8 (C4), 156.8 (C1),
151.8 (C16), 84.8 (C3), 46.5 (C1′′), 44.9 (C1′), 33.8-24.3 (C2′-C11′
,
C2′′-C11′′), 14.6 (C12′, C12′′) (assignments were made based on
HMBC/HMQC spectra). FTIR (cm-1): 3322, 3174, 2954, 2847,
1715, 1667, 1612, 1544. Anal. Calcd for C30H54N6O2-HCl: C,
63.56; H, 9.79; N, 14.83; Cl, 6.25. Found: C, 63.20; H, 9.63; N,
14.71; Cl, 6.21. HRMS (ESI): calcd for (C42H68N6O4 + H+) m/z
531.4381, obsd m/z 531.4383.
Tapping Mode Atomic Force Microscopy. Samples for AFM
imaging were prepared in a Class 10000 Clean Room by spin
coating (Cookson G3-8 Desk-Top Precision Spin Coating System)
25 µL of a 0.25 g/L solution of the RNTs on 1 × 1 cm2 freshly
peeled Mica grade V-4 (SPI supplies) substrates. AFM measure-
ments were performed in tapping mode (TM-AFM) at a scan rate
of 2 Hz per line using a Digital Instruments/Veeco Instruments
MultiMode Nanoscope IV equipped with an E scanner. Silicon
cantilevers (MikroMasch USA, Inc.) with spring constants of 40
N/m were used.
(C3), 67.3 (C6), 41.4, 40.4 (C1′, C1′′), 31.9-22.7 (C2′-C11′
,
C2′′-C11′′), 14.1 (C12′, C12′′). FTIR (cm-1): 3331, 3258, 2953,
2912, 2847, 1631, 1593, 1576, 1539, 1518, 1208, 1111. HRMS
(ESI): calcd for (C36H60N4O2 +H+) m/z 465.3355, obsd m/z
465.3354.
General Procedure for 7f-k. Compound 6f (11.0 g, 15.8 mmol)
was dissolved in THF (130 mL) and the solution cooled to 0 °C in
an ice bath. After addition of Et3N (7 mL, 50.2 mmol) to the
solution, TFAA (4.4 mL, 31.6 mmol) was added over 30 min. After
being stirred for 15 min, the mixture was allowed to warm to rt,
and then it was refluxed for 5 h. After the mixture was cooled to
rt, the reaction was quenched with dH2O and the solvent was
evaporated under reduced pressure (rotavap). The residual solid was
dissolved in ethyl acetate (600 mL), washed with dH2O (3 × 50
mL), 5% aqueous NaHCO3 (2 × 50 mL) and brine (50 mL), and
then dried over anhydrous Na2SO4. The solvent was removed
(rotovap), and the residual solid was precipitated in CH3OH to yield
7f as a white solid (10.2 g, 92% yield). 1H NMR (400 MHz, CDCl3)
δ (ppm):10 7.45-7.26 (m, HC8-HC12, 5H), 5.45 (HC6, s, 2H), 5.36
(HNC1′′, t, J ) 5.2 Hz, 1H), 3.84 (HC1′, m, 2H), 3.48 (HC1′′, dt, J1
) 7.2 Hz, J1 ) 13.2 Hz, 2H), 1.63-1.57 (HC2′ + HC2′′, m, 4H),
1.54 (HC15, s, 9H), 1.34-1.24 (HC3′-HC11′ + HC3′′-HC11′′, m, 32H),
0.89 (HC12′ + HC12′′, t, J ) 7.0 Hz, 6H). 13C NMR (100 MHz,
CDCl3) δ (ppm):10 170.2 (C4), 164.1, 160.7 (C1, C2), 153.3 (C13),
136.5 (C7), 128.4, 128.0, 127.8 (C8-12), 115.0 (C5), 82.1 (C14), 68.5
Electron Microscopy. The samples were prepared by placing a
carbon-coated 400-mesh copper grid on a droplet of 1f (0.25 g/L)
for 5 s. The grid was then blotted and air-dried prior to imaging.
SEM images were obtained without staining at 5-30 kV accelerat-
ing voltage and a working distance of 3.0-6.0 mm on a high
resolution Hitachi S-4800 cold field emission SEM.
Acknowledgment. The support of the Natural Science and
Engineering Research Council, the Alberta Energy Research
Institute, the National Research Council, and the University of
Alberta is gratefully acknowledged.
Supporting Information Available: Experimental proce-
dures and full spectroscopic data for all new compounds. This
material is available free of charge via the Internet at
(C3), 68.2 (C6), 47.3 (C1′), 41.0 (C1′′), 31.8-22.5 (C2′-C11′
,
C2′′-C11′′), 28.2 (HC15), 14.0 (C12′, C12′′). FTIR (cm-1): 3303, 3176,
JO800344B
J. Org. Chem. Vol. 73, No. 11, 2008 4251