Y.-Q. Liu et al./Chemical Papers 65 (5) 739–742 (2011)
Table 1. Spectral data of newly prepared compounds
741
Compound
Spectral data
IR, ν˜/cm−1: 2130 (NC), 1779 (lactone), 1588, 1506, and 1485 (aromatic C C), 930 (OCH2O)
—
VIII
—
1H NMR (CDCl3) δ: 6.91 (s, 1H, H-5), 6.56 (s, 1H, H-8), 6.26 (s, 2H, H-2ꢀ,6ꢀ), 6.03 (dd, J = 7.9 Hz, J = 1.1 Hz, 2H,
OCH2O), 4.99 (d, J = 4.4 Hz, 1H, H-4), 4.68 (d, J = 5.1 Hz, 1H, H-1), 4.39 (m, 2H, H-11), 3.81 (s, 3H, 4ꢀ-OCH3),
3.75 (s, 6H, 3ꢀ,5ꢀ —OCH3), 3.20 (q, 1H, H-2), 2.96 (m, 1H, H-3)
13C NMR: (CDC13) δ: 173.01, 160.01, 152.78, 149.27, 147.95, 137.64, 134.32, 131.59, 125.13, 110.53, 108.71, 108.33,
101.95, 67.69, 60.73, 56.35, 53.53, 43.53, 41.37, 35.24
MS(EI) (m/z): 424 (M+1)
HRMS (m/z) for C23H21NO7 [M+NH4]+: calc. 441.1656, found 441.1652
IR, ν˜/cm−1: 3447 (OH), 2130 (NC), 1745 (lactone), 1600, 1500, and 1480 (aromatic C C), 933 (OCH2O)
—
XI
—
1H NMR (CDCl3) δ: 6.88 (s, 1H, H-5), 6.50 (s, 1H, H-8), 6.32 (s, 2H, H-2ꢀ,6ꢀ), 5.98 (dd, J = 7.9 Hz, J = 1.1 Hz, 2H,
OCH2O), 4.92 (d, J = 4.4 Hz, 1H, H-4), 4.68 (d, J = 5.1 Hz, 1H, H-1), 4.37 (m, 2H, H-11), 3.78 (s, 6H, 3ꢀ,5ꢀ-OCH3),
3.15 (q, 1H, H-2), 2.80 (m, 1H, H-3)
13C NMR: (CDC13) δ: 175.40, 160.01, 152.78, 149.27, 146.30, 137.64, 134.12, 133.95, 125.13, 110.53, 108.71, 108.33,
101.95, 67.69, 60.73, 56.35, 53.53, 43.70, 41.37, 38.02
MS(EI) (m/z): 410 (M+1)
HRMS (m/z) for C22H19NO7 [M+NH4]+: calc. 427.1843, found 427.1825
tions and heterocycles built from isocyanides.
5 min, the ice-bath was removed and the mixture was
stirred at room temperature for 8 h. The yellow solu-
tion slowly turned brown. The solution was quenched
by an addition of water (10 mL) and extracted with
CH2Cl2 (3 × 15 mL). The organic layer was washed
with a saturated aqueous solution of NaHSO4 (2 ×
15 mL); the extracts were dried (MgSO4), filtered, the
reaction solvent was evaporated and chromatographed
on silica-gel (hexane/ethyl acetate, ϕr = 9 : 1, then 8
: 2, and 7 : 3) to give compounds VIII and XI as white
solids in ≈ 35–37 % yields.
Melting points were taken on a Kofler melting
point apparatus (Triumph Company, Germany) and
are uncorrected; IR spectra were obtained on a NIC-
5DX spectrophotometer (Nicote Company, USA);
mass spectral analysis was performed on a ZAB-HS
and Bruker Daltonics APEXII49e instrument (Bruker
Company, USA). Optical rotations were determined
on a Perkin–Elmer Model 341 spectropolarimeter
(Taike Company, China). NMR spectra were recorded
on a Bruker AM-400 spectrometer (Bruker Com-
pany, USA) at 400 MHz using TMS as the reference.
Sonication was performed in a Shanghai Branson-
CQX (Shanghai Branson Company, China) ultrasonic
cleaner at the frequency of 25 kHz and nominal power
of 500 W. The reaction flask was located in the maxi-
mum energy area of the cleaner, where the surface of
reactants (reaction vessel) is slightly lower than the
level of water; addition or removal of water was used
to control the temperature of the water bath. Chem-
icals are commercially available and were used with-
out further purification. The starting materials of 4β-
aminopodophyllotoxins (IV, V) were prepared by the
above procedures in our laboratory (Yu et al., 1999;
Liu et al., 2010).
General procedure for 4β-isocyanopodophylloto-
xins (VIII, XI ) preparation: in method A (classi-
cal method), to a solution of 0.24 mmol of 4β-
aminopodophyllotoxins (IV, V ) in 10 mL of CH2Cl2,
5 mL of ethyl formate were added and the reac-
tion mixture was refluxed for 4 h. The solvents
were then evaporated under reduced pressure, and
the residue was purified by flash chromatography
(CH2Cl2/MeOH, ϕr = 98 : 2) to give 4β-formamido-4-
deoxypodophyllotoxins (VI, VII ) in ≈ 45–47 % yields.
Subsequently, to a cooled and stirred solution of 0.31
mmol of formamide (VI, VII ) in pyridine (5 mL), 0.77
mmol of p-toluenesulfonyl chloride was added. After
In method B (ultrasound irradiation), to a solution
of 0.24 mmol of 4β-aminopodophyllotoxins (IV, V ) in
10 mL of CH2Cl2, 5 mL of ethyl formate were added
and the above mixture was irradiated by an ultrasonic
generator in a water bath at 30◦C for 1 h. Progress of
the reaction was monitored by TLC. After completion
of the reaction, the solvents were evaporated under re-
duced pressure, and the residue was purified by flash
chromatography (CH2Cl2/MeOH, ϕr = 98 : 2) to give
4β-formamido-4-deoxypodophyllotoxins (VI, VII ) in
≈ 78–80 % yields. Subsequently, to a cooled and
stirred solution of 0.31 mmol of formamide (VI, VII )
in 5 mL of pyridine, 0.77 mmol of p-toluenesulfonyl
chloride was added. After 5 min, the ice-bath was re-
moved and the mixture was sonicated at room temper-
ature for 2 h. The yellow solution slowly turned brown.
The solution was quenched by an addition of water
(10 mL) and extracted with CH2Cl2 (3 × 15 mL).
The organic layer was washed with a saturated aque-
ous solution of NaHSO4 (2 × 15 mL), the extracts
were dried (MgSO4), filtered, concentrated, and chro-
matographed on silica-gel (hexane/ethyl acetate, ϕr =
9 : 1, then 8 : 2, and 7 : 3) to give compounds VIII
and XI as white solids in ≈ 65–67 % yields. Charac-
terization data of newly prepared compounds: VIII,
yield: 67 %, m.p. = 115–117◦C; XI, yield: 65 %, m.p.
= 187–189◦C. Spectral data are listed in Table 1.