Synthesis of the Monosaccharide Kedarosamine
J . Org. Chem., Vol. 63, No. 2, 1998 285
0.035, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 7.80-7.29 (m,
13H), 5.62 (d, 1H, J ) 6.0 Hz), 5.07 (d, 1H, J ) 8.8 Hz), 4.60
(bq, 1H, J ) 6.3 Hz), 4.53 (dd, 1H, J ) 7.0 and 10.6 Hz), 4.47
(dd, 1H, J ) 6.6 and 10.6 Hz), 4.25 (t, 1H, J ) 6.7 Hz), 4.41
(m, 1H), 3.96 (m, 1H), 2.61 (bs, 1H), 2.17 (dd, 1H, J ) 6.0 and
13.8 Hz), 2.02 (ddd, 1H, J ) 6.0, 12.0, and 13.8 Hz), 1.17 (d,
3H, J ) 6.5 Hz); 13C NMR (CDCl3, 100 MHz) δ 158.2, 143.8,
143.62, 141.3, 141.3, 134.7, 131.3, 129.0, 127.8, 127.3, 127.1,
125.0, 125.0, 120.0, 84.1, 67.0, 65.7, 55.2, 47.2, 33.6, 17.0; HR
FABMS calcd for C27H27NNaO4S (M + Na) 484.1559, found
484.1550.
Rf 0.51 (heptane:ethyl acetate 2:1); [R]23D -65.8° (c 1.0, CHCl3);
1H NMR (CDCl3, 400 MHz) δ 7.78-7.17 (m, 18H), 5.41 (ddd,
1H, J ) 3.8, 5.1, and 12.3 Hz), 5.04 (d, 1H, J ) 9.8 Hz), 4.78
(d, 1H, J ) 3.4 Hz), 4.76 (dd, 1H, J ) 4.0 and 7.8 Hz), 4.50
(dq, 1H, J ) 1.1 and 6.5 Hz), 4.43 (dd, 1H, J ) 7.5 and 10.6
Hz), 4.39 (dd, 1H, J ) 6.8 and 10.6 Hz), 4.26 (t, 1H, J ) 7.0
Hz), 4.08 (dd, 1H, J ) 2.9 and 9.8 Hz), 3.90 (dd, 1H, J ) 7.9
and 10.8 Hz), 3.67 (dd, 1H, J ) 4.0 and 10.8 Hz), 1.99-1.90
(m, 1H), 1.77 (dt, 1H, J ) 3.9 and 12.8 Hz), 1.12 (d, 3H, J )
6.5 Hz), 1.06 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 170.3,
156.7, 143.9, 143.8, 141.3, 138.15, 135.6, 135.5, 133.3, 133.2,
129.7, 129.7, 129.0, 128.4, 128.2, 128.2, 127.8, 127.7, 127.7,
127.0, 125.3, 125.1, 125.0, 120.0, 120.0, 93.9, 78.3, 68.0, 67.6,
66.7, 64.7, 51.8, 47.2, 30.1, 26.8, 21.1, 19.2, 17.0; HR FABMS
calcd for C47H51NNaO7Si (M + Na) 792.3333, found 792.3348.
(R)-2-(ter t-Bu tyld ip h en ylsilyloxy)-1-p h en yleth yl 3-O-
Acetyl-4-ben zyloxycar bon ylam in o-2,4,6-tr ideoxy-r-L-lyxo-
h exop yr a n osid e (16b). BF3‚Et2O (4 × 37 µL, 4 × 0.293
mmol) was added in portions to a solution of 15b (107 mg,
0.293 mmol) and 13 (121 mg, 0.322 mmol) in toluene (5 mL)
at 0 °C. After stirring for 2 h, the solution was poored into
EtOAc and washed with saturated aqueous NaHCO3. The
organic layer was separated, dried with Na2SO4, filtered, and
concentrated. The crude product was purified by flash chro-
matography (heptane:ethyl acetate 9:1 + 5% pyridine) to give
1,3-Di-O-a cetyl-2,4,6-tr id eoxy-4-(9-flu or en ylm eth oxy-
ca r bon yla m in o)-L-lyxo-h exop yr a n ose (15a ). A solution of
10a (30.0 mg, 81 µmol) in pyridine (1 mL) and acetic acid (1
mL) was stirred overnight. The solvents were then removed,
and the residue was purified by flash chromatography (hep-
tane:ethyl acetate 5:2) to give 15a (33.2 mg, 90%) as an R/â
mixture (1.4:1) which had Rf 0.60 (heptane:ethyl acetate 2:1).
1
R-anomer: [R]23 -23.5° (c 0.5, CHCl3); H NMR (CDCl3, 400
D
MHz) δ 7.88-7.39 (m, 8H), 6.31 (bs, 1H), 5.32 (ddd, 1H, J )
3.6, 6.8, and 10.8 Hz), 5.08 (d, 1H, J ) 9.8 Hz), 4.55 (ABX-
type dd, 1H, J ) 7.2 and 10.7 Hz), 4.50 (dd, 1H, J ) 6.8 and
10.7 Hz), 4.34 (t, 1H, J ) 7.8 Hz), 4.32 (dq, 1H, J ) 1.4 and
6.3 Hz), 4.23 (bdd, 1H, J ) 2.9 and 9.8 Hz), 2.20 (s, 3H), 2.07-
2.01 (m, 2H), 1.24 (d, 3H, J ) 6.4 Hz); 13C NMR (CDCl3, 100
MHz) δ 170.5, 169.2, 156.7, 143.8, 143.7, 141.4, 141.3, 127.8,
127.1, 125.0, 124.9, 120.1, 120.0, 91.4, 67.4, 66.9, 66.8, 51.4,
47.2, 28.9, 21.1, 21.0, 16.9; FABMS m/z (rel intensity) 479 (4),
460 (84), 393 (3), 349 (5), 329 (20), 199 (13), 176 (100), 173
(15), 154 (12), 136 (10), 92 (7), 23 (21). â-anomer: [R]23D -31.0°
(c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 7.88-7.38 (m,
8H), 5.81 (dd, 1H, J ) 2.6 and 10.22 Hz), 5.18 (d, 1H, J ) 9,9
Hz), 5.06 (ddd, 1H, J ) 3.9, 4.9, and 12.6 Hz), 4.54 (dd, 1H, J
) 7.3 and 10.7 Hz), 4.48 (dd, 1H, J ) 6.8 and 10.7 Hz), 4.34 (t,
1H, J ) 7.0 Hz), 4.16 (dd, 1H, J ) 3.6 and 10.0 Hz), 3.89 (dq,
1H, J ) 1.4 and 6.4 Hz), 2.23 (s, 3H), 2.14 (ddd, 1H, J ) 2.7,
5.1, and 12.6 Hz), 2.07 (s, 3H), 1.85 (dt, 1H, J ) 10.3 and 12.6
Hz), 1.31 (d, 3H, J ) 6.4 Hz); 13C NMR (CDCl3, 100 MHz) δ
170.2, 168.8, 156.6, 143.9, 143.7, 141.3, 127.7, 127.0, 125.1,
125.0, 120.1, 120.0, 91.8, 70.8, 69.0, 66.8, 50.7, 47.2, 30.5, 21.0,
16b (124 mg, 62%): Rf 0.42 (heptane:ethyl acetate 2:1); [R]23
D
-82.4° (c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 7.70-7.24
(m, 20H), 5.41 (ddd, 1H, J ) 3.9, 5.0, and 12.3 Hz), 5.17 (d,
1H, J ) 12.3 Hz), 5.09 (d, 1H, J ) 12.3 Hz), 5.04 (d, 1H, J )
9.9 Hz), 4.77-4.74 (m, 2H), 4.50 (dq, 1H, J ) 1.3 and 6.4 Hz),
4.09 (dd, 1H, J ) 3.2 and 9.9 Hz), 3.89 (dd, 1H, J ) 7.9 and
10.8 Hz), 3.66 (dd, 1H, J ) 4.1 and 10.8 Hz), 1.99 (s, 3H), 1.92
(dd, 1H, J ) 5.3 and 13.2 Hz), 1.73 (dt, 1H, J ) 3.8 and 12.9
Hz), 1.13 (d, 3H, J ) 6.4 Hz), 1.06 (s, 9H); 13C NMR (CDCl3,
100 MHz) δ 170.3, 156.7, 138.2, 136.59, 135.5, 135.5, 133.3,
133.2, 129.7, 129.7, 128.5, 128.4, 128.3, 128.1, 127.9, 127.7,
127.7, 127.4, 93.9, 78.2, 68.0, 67.9, 66.7, 64.7, 51.8, 30.1, 26.78,
21.0, 19.1, 17.0; HR FABMS calcd for C40H47NNaO7Si (M +
Na) 704.3020, found 704.3008.
(R)-2-(ter t-Bu tyldiph en ylsilyloxy)-1-ph en yleth yl 4-Ben z-
yloxyca r bon yla m in o-2,4,6-tr id eoxy-r-L-lyxo-h exop yr a n o-
sid e (14b). A solution of 16b (194 mg, 0.284 mmol) in 0.02
M methanolic NaOMe (2.5 mL) was stirred for 5 h. The
solution was then neutralized by addition of Doulite C436, and
the mixture was stirred for 1 h and then filtrated and
concentrated. The crude product was purified by flash chro-
matography (heptane:ethyl acetate 5:1 + 5% pyridine) to give
20.9, 16.8; HR FABMS calcd for
492.1425, found 492.1443.
C25H27KNO7 (M + K)
1,3-D i-O -a c e t y l-4-b e n zy lo x y c a r b o n y la m in o -2,4,6-
tr id eoxy-L-lyxo-h exop yr a n ose (15b). The synthesis was
carried out as described for 15a to give 15b in 87% yield as
an R/â mixture (1:1.3) after purification by flash chromatog-
raphy (heptane:ethyl acetate 2:1). Rf 0.63 (heptane:ethyl
acetate 1:2). R-anomer: 1H NMR (CDCl3, 400 MHz) δ 7.38-
7.31 (m, 5H), 6.19 (dd, 1H, J ) 2.2 Hz), 5.22 (ddd, 1H, J )
3.6, 6.3, and 11.4 Hz), 5.15 (d, 1H, J ) 12.3 Hz), 5.07 (d, 1H,
J ) 12.3 Hz), 5.04 (d, 1H, J ) 10.0 Hz), 4.22 (dq, 1H, J ) 1.4
and 6.5 Hz), 4.15 (dd, 1H, J ) 3.1 and 10.0 Hz), 2.10 (s, 3H),
2.06-1.98 (m, 2H), 1.96 (s, 3H), 1.17 (d, 3H, J ) 6.5 Hz); 13C
NMR (CDCl3, 100 MHz) δ 170.4, 169.3, 156.6, 136.4, 128.5,
128.2, 128.0, 91.4, 69.0, 67.4, 66.9, 51.4, 28.8, 21.5, 20.9, 16.9.
â-anomer: 1H NMR (CDCl3, 400 MHz) δ 7.38-7.31 (m, 5H),
5.70 (dd, 1H, J ) 2.6 and 10.2 Hz), 5.17 (d, 1H, J ) 12.3 Hz),
5.12 (d, 1H, J ) 10.0 Hz), 5.07 (d, 1H, J ) 12.3 Hz), 4.98 (ddd,
1H, J ) 3.7, 5.0, and 12.6 Hz), 4.07 (dd, 1H, J ) 3.7 and 10.0
Hz), 3.79 (dq, 1H, J ) 1.4 and 6.4 Hz), 2.11 (s, 3H), 1.95 (s,
3H), 1.95-1.90 (m, 1H), 1.74 (dt, 1H, J ) 10.3 and 12.6 Hz),
1.24 (d, 3H, J ) 6.4 Hz); 13C NMR (CDCl3, 100 MHz) δ 170.2,
168.8, 156.6, 136.5, 128.5, 128.1, 127.9, 91.7, 70.6, 66.9, 66.8,
50.6, 30.4, 20.9, 20.8, 16.8. HR FABMS calcd for C18H23NNaO7
(M + Na) 388.1372, found 388.1364.
(R)-2-(ter t-Bu tyld ip h en ylsilyloxy)-1-p h en yleth yl 3-O-
Acetyl-2,4,6-tr ideoxy-4-(9-flu or en ylm eth oxycar bon ylam i-
n o)-r-L-lyxo-h exop yr a n osid e (16a ). BF3‚Et2O (170 µL, 1.35
mmol) was added to a solution of 15a (614 mg, 0.35 mmol)
and 13 (561 mg, 1.49 mmol) in toluene (30 mL) at 0 °C. After
stirring for 1 h the solution was poured into EtOAc and washed
with saturated aqueous NaHCO3. The organic layer was
separated, dried with Na2SO4, filtered, and concentrated. The
crude product was purified by flash chromatography (heptane:
ethyl acetate 7:1 + 5% pyridine) to give 16a (1.042 g, 80%):
14b (142 mg, 78%): Rf 0.20 (heptane:ethyl acetate 2:1); [R]23
D
-87.4° (c 0.95, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 7.78-
7.31 (m, 20H), 5.21 (d, 2H, J ) 3.0 Hz), 5.16 (d, 1H, J ) 9.1
Hz), 4.83 (dd, 1H, J ) 3.6 and 8.3 Hz), 4.79 (d, 1H, J ) 3.5
Hz), 4.53 (bq, 1H, J ) 6.5 Hz), 4.41 (m, 1H), 3.95 (m, 1H),
3.95 (dd, 1H, J ) 8.3 and 10.8 Hz), 3.72 (dd, 1H, J ) 3.9 and
10.8 Hz), 2.59 (bs, 1H), 2.04 (dd, 1H, J ) 5.1 and 13.4 Hz),
1.65 (dt, 1H, J ) 3.5 and 12.6 Hz), 1.22 (d, 3H, J ) 6.5 Hz),
1.12 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 158.3, 138.2, 136.1,
135.5, 133.3, 133.3, 129.7, 128.6, 128.4, 128.3, 128.3, 128.1,
128.1, 128.0, 127.7, 127.7, 127.4, 94.1, 78.1, 68.2, 67.3, 66.4,
64.5, 55.2, 33.1, 26.8, 19.1, 17.2; HR FABMS calcd for C38H45
-
NNaO6Si (M + Na) 662.2914, found 662.2923.
(R)-2-Hydr oxy-1-ph en yleth yl 4-Ben zyloxycar bon ylam i-
n o-2,4,6-tr id eoxy-r-L-lyxo-h exop yr a n osid e (17). QF‚3H2O
(63.1 mg, 0.200 mmol) was added to a solution of 14b (128
mg, 0.200 mmol) in THF (5 mL), and the solution was stirred
overnight. The solution was concentrated and the crude
product was purified by flash chromatography (heptane:ethyl
acetate 1:3 + 5% pyridine) to give 17 (53.0 mg, 66%): Rf 0.60
1
(chloroform:methanol 9:1); [R]23 -140.9° (c 0.80, CHCl3); H
D
NMR (CDCl3, 400 MHz) 7.38-7.30 (m, 10H), 5.17-5.10 (m,
2H), 5.12 (d, 1H, J ) 9.1 Hz), 4.79 (d, 1H, 3.8 Hz), 4.71 (dd,
1H, J ) 3.8 and 8.2 Hz), 4.31 (m, 2H), 3.96 (bd, 1H, J ) 7.2
Hz), 3.75 (bt, 1H, J ) 9.9 Hz), 3.69 (m, 1H), 2.73 (bs, 1H), 2.29
(bs, 1H), 1.97 (dd, 1H, J ) 5.1 and 13.3 Hz), 1.60 (ddd, 1H, J
) 4.0, 12.2, and 13.3 Hz), 1.24 (d, 3H, J ) 6.5 Hz); 13C NMR
(CDCl3, 100 MHz) δ 158.3, 137.6, 136.0, 128.6, 128.6, 128.4,