1
dd, J = 4.7, 7.3 Hz), 4.40 (1 H, m), 4.63 (1 H, d, J = 4.7 Hz), 4.85
(1 H, br s), 5.08–5.17 (4 H, m), 5.74 (1 H, d, J = 7.7 Hz), 5.82 (1 H,
m), 6.65 (1 H, s), 7.29–7.34 (5 H, m), 9.02 (1 H, d, J = 8.8 Hz);
13C-NMR (100 MHz, CDCl3) d 10.1, 11.2, 16.4, 16.4, 20.1, 26.9,
29.5, 33.8, 36.0, 49.6, 50.6, 63.0, 66.6, 70.1, 114.3, 127.8, 127.8,
128.3, 136.5, 137.4, 155.4, 168.5, 170.8, 171.9; HRMS (EI) calcd
for C26H35N3O6: 485.2525 (M+), found 485.2525 (M+).
[a]17 +106.05 (c 1.06, CHCl3); H-NMR (500 MHz, CDCl3) d
D
0.56–0.62 (2 H, m), 0.90 (1 H, m), 1.24–1.34 (10 H, m), 3.16 (1 H,
dd, J = 7.2, 13.1 Hz), 3.21–3.28 (2 H, m), 3.34 (1 H, d, J = 4.5 Hz),
5.17 (1 H, d, J = 10.4 Hz), 5.28 (1 H, d, J = 17.2 Hz), 5.89 (1 H,
m); 13C-NMR (125 MHz, CDCl3) d 8.4, 17.5, 21.6, 22.6, 54.5, 55.6,
61.3, 116.7, 138.1; HRMS (FAB) calcd for C11H21N4OS: 257.1436
[(M+H)+], found 257.1425 [(M+H)+].
Belactosin A (2)
(1S,2S)-2-Azidomethyl-1-[(1R)-1-(N-Cbz-L-alanyl)amino-2-
propenyl]cyclopropane (28)
A mixture of 11 (43 mg, 88 mmol), NaIO4 (94 mg, 440 mmol),
KMnO4 (9.7 mg, 62 mmol), NaHCO3 (7.4 mg, 88 mmol) in aqueous
acetone (67%, 3 mL) was stirred at room temperature for 17 h. The
mixture was diluted with AcOEt and washed with aqueous HCl
(1 M, 4 times), and the organic layer was washed with brine, dried
(Na2SO4), and evaporated. A solution of the residue in MeOH
(1 mL) was passed through a short column (Diaion-PK212L,
H+ form, aqueous 50% MeOH to give N-Cbz-belactosin A as
a white solid. A mixture of the obtained N-Cbz-belactosin A and
Pd/C (10%, 43 mg) in HCO2H/THF (2:3, 5 mL) was stirred
under atmospheric pressure of H2 at room temperature for 2 h,
and then the catalysts were filtered off with Celite and washed
with CH2Cl2. The filtrate was evaporated, and the residue was
co-evaporated with toluene/MeOH (2:1), and the residue was
purified by column chromatography (C18-reverse phase silica gel;
10% aqueous MeCN) to give belactosin A (2, 25 mg, 77%) as a
A solution of 27 (25 mg, 100 mmol) and HCl (4 M in AcOEt,
100 mL) in MeOH (1.0 mL) was stirred at room temperature
for 10 min and then evaporated to give the corresponding
sulfinylamino-removed product as an oil. From the product, com-
pound 28 (32 mg, 88%, white amorphous solid) was synthesized
as described for the synthesis of 23: [a]18 +1.66 (c 0.96, CHCl3);
D
1H-NMR (500 MHz, CDCl3) d 0.57 (1 H, m), 0.64 (1 H, m), 0.87
(1 H, m), 1.23 (1 H. m), 1.41 (1 H, d), 2.89 (1 H, dd, J = 8.2, 12.5
Hz), 3.26 (1 H, dd, J = 6.0, 12.5 Hz), 3.95 (1 H, m), 4.26 (1 H, m),
5.09–5.26 (5 H, m), 5.80 (1 H, br s), 6.21 (1 H, br s), 7.29–7.39
(5 H, m); 13C-NMR (125 MHz, CDCl3) d 9.0, 15.8, 18.4, 21.9,
29.4, 50.7, 54.1, 54.4, 67.1, 89.4, 115.4, 128.1, 128.3, 128.5, 136.4,
171.5; HRMS (FAB) calcd for C18H24N5O3: 358.1879 [(M+H)+],
found 358.1874 [(M+H)+].
1
white amorphous solid, the H NMR spectrum of which was in
(1S,2S)-2-tert-Butoxycarbonylaminomethyl-1-[(1R)-1-(N-Cbz-L
-alanyl)amino-2-propenyl]cyclopropane (29)
accord with that of natural belactosin A:15 [a]23 +4.94 (c 0.95,
D
H2O) [lit.5a [a]27 +4.8 (c 0.37, H2O)]; 1H-NMR (500 MHz, D2O)
D
d 0.66 (1 H, m), 0.79 (1 H, m), 0.83 (3 H, t, J = 7.5 Hz), 0.90
(1 H, m), 0.95 (3 H, d, J = 6.7 Hz), 1.27 (1 H, m), 1.48 (1 H,
m), 1.51 (3 H, d, J = 7.0 Hz), 1.58 (1 H, m), 1.86 (1 H, m), 1.97
(1 H, m), 2.46 (1 H, m), 3.80 (1 H, dd, J = 3.6, 7.3 Hz), 4.08
(1 H, q, J = 7.1 Hz), 4.28 (1 H, t, J = 5.1 Hz), 4.81 (1 H, d, J
= 4.3); 13C-NMR (125 MHz, D2O) d 11.0, 11.9, 16.2, 16.6, 17.2,
26.9, 29.0, 33.5, 34.4, 49.8, 55.6, 62.5, 71.8, 170.5, 172.44, 173.2,
178.3; LRMS (FAB) m/z 370 [(M+H)+]; HRMS (FAB) calcd for
C17H27N3O6: 370.1978 [(M+H)+], found 370.1974 [(M+H)+].
A mixture of 28 (138 mg, 0.38 mmol) and PPh3 (131 mg,
0.50 mmol) in 80% aqueous THF (3 mL) was stirred at room
temperature for 2 h. To the mixture was added (Boc)2O (350 mL)
and the resulting mixture was further stirred at room temperature
for 2 h. The mixture was partitioned between AcOEt and H2O,
and the organic layer was washed with brine, dried (Na2SO4), and
evaporated. The residue was purified by column chromatography
(silica gel; hexane/AcOEt, 4:1 then 2:1) to give 29 (149 mg, 90%)
1
as a white amorphous solid: [a]22 +24.76 (c 1.00, CHCl3); H-
D
NMR (400 MHz, DMSO-d6) d 0.34 (2 H, m), 0.80 (2 H, m), 1.20
(3 H, d, J = 7.1 Hz), 1.35 (9 H, s), 2.80 (2 H, m), 3.89 (1 H, m),
4.03 (1 H, m), 4.98–5.09 (4 H, m), 5.76 (1 H, m), 6.74 (1H, br s),
7.31–7.35 (6 H, m), 7.77 (1 H, d); 13C-NMR (100 MHz, CDCl3) d
8.8, 17.1, 18.4, 22.2, 27.4, 28.4, 44.3, 50.5, 54.9, 66.9, 79.2, 115.0,
128.0, 128.1, 128.4, 136.1, 136.6, 155.9, 171.6; HRMS (EI) calcd
for C23H33N3O5: 431.2420 (M+), found 431.2421 (M+).
(1S,2S)-2-Azidomethyl-1-[(1R)-1-((S)-tert-butylsulfinyl)amino-2-
propenyl]cyclopropane (27)
A mixture of 199 (2.82 g, 6.0 mmol) and TBAF (1.0 M in THF,
12 mL) in THF (48 mL) was stirred at room temperature for
14 h and then evaporated. The residue was purified by column
chromatography (silica gel; CHCl3/MeOH = 100:0 then 97:3)
to give the corresponding de-silylated product as a white solid.
A solution of the solid, DPPA (2.6 mL, 12 mmol) and DBU
(1.9 mL, 12 mmol) in THF (60 mL) was stirred at 0 ◦C for 10 min
and then at room temperature for 6 h. The resulting mixture
was concentrated in vacuo and partitioned between AcOEt and
saturated aqueous NH4Cl, and the organic layer was washed with
brine, dried (Na2SO4), and evaporated. A mixture of the residue,
NaN3 (520 mg, 8.0 mmol), and 15-crown-5 (1.8 mL, 8.0 mL) in
DMF (60 mL) was stirred at room temperature for 24 h and then
evaporated. The residue was partitioned between AcOEt and H2O,
and the organic layer was washed with brine, dried (Na2SO4), and
evaporated. The residue was purified by column chromatography
(silica gel; hexane/AcOEt, 2:1) to give 27 (1.39 g, 89%) as an oil:
Compound 30
Compound 30 (135 mg, 80%, white amorphous solid) was
prepared from 29 (149 mg, 345 mmol) as described for the synthesis
of 11: [a]22D +15.21 (c 1.12, CHCl3); 1H-NMR (400 MHz, CDCl3)
d 0.53–0.57 (2 H, m), 0.80 (1 H), 0.93 (3 H, t, J = 7.4), 1.03–1.05
(4 H, m, H-2), 1.29 (1 H, m), 1.39 (3 H, d, J = 7.1 Hz), 1.65 (1 H,
m), 1.94 (1 H, m), 2.82 (1 H, m), 3.38 (1 H, m), 3.58 (1 H, dd, J =
4.5, 7.7 Hz), 3.68 (1 H, m), 4.20 (1 H, m), 4.64 (1 H, d, J =
4.5 Hz), 5.09–5.22 (4 H, m), 5.66 (1 H, br s), 5.77 (1 H, m), 6.99
(2 H, br s), 7.29–7.36 (5 H, m); 13C-NMR (100 MHz, CDCl3) d
9.3, 11.0, 16.3, 17.1, 18.4, 23.0, 26.6, 33.8, 43.6, 50.7, 55.5, 62.8,
66.9, 70.9, 115.3, 127.8, 128.0, 128.4, 136.1, 136.6, 156.0, 168.2,
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1868–1877 | 1875
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