Total Synthesis of Caloporoside
J . Org. Chem., Vol. 63, No. 9, 1998 3079
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(s, 2H), 4.99 (m, 1H), 4.66-4.77 (m, 4H), 4.45 (s, 2H), 4.17 (m,
1H), 4.03 (dA, J ) 7.6, 2.5, 1H), 3.93 (dB, J ) 7.6, 3.0, 1H),
3.79 (dd, J ) 9.6, 5.7, 1H), 3.53 (dd, J ) 9.6, 5.4, 1H), 2.52 (m,
2H), 1.97 (s, 3H), 1.14-1.60 (bs, 28H), 1.15 (d, J ) 6.3, 3H),
0.89 (s, 9H), 0.11 (s, 3H), 0.09 (s, 3H); 13C NMR (CDCl3, 75
MHz) δ 169.9, 168.2, 167.5, 155.5, 141.9, 141.6, 139.1, 138.5,
138.2, 136.8, 135.7, 130.1, 128.6, 128.4, 128.4, 128.2, 128.2,
128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.4, 127.4, 127.3,
127.1, 124.0, 121.8, 109.9, 82.5, 79.9, 75.2, 74.4, 73.7, 73.3, 72.7,
72.6, 71.7, 70.4, 66.9, 35.9, 33.4, 31.2, 29.7, 29.6, 29.5, 29.5,
25.8, 25.2, 20.7, 19.7, 18.0, -4.6, -4.7; MS (ESI) 1194 ([M +
NH4]+); C73H96O11Si (1177.64) calcd 74.45, H 8.22, found C
74.54, H 8.26.
1028, 737, 698; H NMR (CDCl3, 300 MHz) δ 7.17-7.39 (m,
41H), 6.79 (d, J ) 7.7, 1H), 6.75 (d, J ) 8.3, 1H), 5.32 (s, 2H),
5.21 (d, J ) 2.0, 1H), 5.00-5.05 (m, 3H), 4.92 (m, 1H), 4.77-
4.83 (m, 2H), 4.72 (d, J ) 8.0, 1H), 4.50-4.67 (m, 6H), 4.50 (A
part of AB, J ) 12.1, 1H), 4.38-4.42 (m, 3H), 4.20 (m, 1H),
4.03 (m, 2H), 3.84 (m, 1H), 3.55-3.79 (m, 7H), 3.43 (m, 1H),
2.52 (m, 2H), 1.94 (s, 3H), 1.13 (d, J ) 6.3, 3H), 1.07-1.72 (bs,
28H); 13C NMR (CDCl3, 75 MHz) δ 169.8, 168.1, 168.0, 165.8,
155.4, 141.5, 138.5, 138.1, 138.1, 138.0, 137.9, 137.8, 136.8,
135.7, 130.1, 128.5, 128.4, 128.3, 128.3, 128.1, 128.1, 128.0,
127.9, 127.8, 127.8, 127.7, 127.6, 127.5, 127.4, 127.4, 127.0,
123.9, 121.7, 109.8, 100.2, 82.6, 79.8, 79.1, 78.7, 77.9, 75.0, 74.9,
74.5, 74.2, 73.4, 73.3, 72.8, 70.3, 68.5, 66.8, 40.5, 35.7, 33.4,
31.2, 29.6, 29.5, 29.5, 29.4, 29.4, 25.1, 20.4, 19.5; gated NMR
(CDCl3, 75 MHz) J C1′,H1′ ) 160.2; MS (ESI) 1570 ([M + Na]+);
Com p ou n d 30. KOAc (450 mg, 4.59 mmol) was added to
a solution of the triflate 27 (702 mg, 0.55 mmol, prepared as
described above) in DMF (10 mL) at 0 °C. The mixture was
allowed to reach rt over a period of 2 h. A standard extractive
workup followed by flash chromatography (hexane/ethyl
acetate 4:1) afforded the tetrahydrofuran derivative 30 as a
colorless syrup (414 mg, 75%) as well as compound 28 as a
C
96H111ClO17 (1572.37) calcd C 73.33, H 7.12, found C 73.39,
H 7.12.
Disa cch a r id e 32. A solution of glycoside 31 (234 mg, 0.15
mmol), thiourea (170 mg, 2.23 mmol), and NaHCO3 (94 mg,
1.12 mmol) in CH2Cl2 (2 mL) and EtOH (10 mL) was refluxed
for 4 h. After addition of ethyl acetate (50 mL), the mixture
was washed with water (2 × 30 mL) and the organic layers
were dried over Na2SO4. Removal of the solvents followed by
flash chromatography (hexane/ethyl acetate 4:1) provided
compound 32 as a colorless syrup (167 mg, 75%): [R]25D -1.8°
(c 6.6, CHCl3); IR 3456, 2925, 2854, 1734, 1454, 1268, 1109,
minor byproduct (117 mg, 18%). Data of compound 30: [R]25
D
+8.9° (c 6.4, CHCl3); IR 2926, 2854, 1728, 1583, 1454, 1269,
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1108, 736, 697; H NMR (CDCl3, 300 MHz) δ 7.18-7.34 (m,
26H), 6.75-6.81 (m, 2H), 5.32 (s, 2H), 5.05 (s, 2H), 4.95 (m,
1H), 4.60-4.64 (m, 2H), 4.55 (s, 2H), 4.46-4.50 (m, 3H), 4.39
(m, 1H), 4.31 (m, 1H), 4.03 (dd, J ) 4.2, 1.8, 1H), 3.64 (dA
part of AB, J ) 10.3, 5.4, 1H), 3.60 (dB part of AB, J ) 10.3,
5.8, 1H), 2.52 (m, 2H), 1.13-1.67 (bs, 28H), 1.18 (d, J ) 6.2,
3H); 13C NMR (CDCl3, 75 MHz) δ 170.5, 168.2, 155.4, 141.8,
141.5, 138.1, 137.6, 137.3, 136.8, 135.7, 130.1, 128.5, 128.4,
128.3, 128.1, 127.8, 127.8, 127.7, 127.6, 127.5, 127.0, 124.0,
121.7, 109.9, 86.6, 83.6, 82.9, 81.4, 73.3, 72.4, 71.7, 71.6, 70.3,
69.7, 66.9, 35.7, 33.4, 31.2, 29.6, 29.6, 29.5, 29.5, 29.4, 25.3,
19.8; MS (ESI) 1020 ([M + NH4]+), 1025 ([M + Na]+), 1041
([M + K]+); C65H78O9 (1003.32) calcd C 77.81, H 7.84, found C
77.72, H 7.84.
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1065, 736, 697; H NMR (CDCl3, 300 MHz) δ 7.14-7.41 (m,
41H), 6.79 (d, J ) 6.8, 1H), 6.76 (d, J ) 8.3, 1H), 5.32 (s, 2H),
5.30 (d, J ) 4.2, 1H), 5.05 (s, 2H), 4.79 and 4.99 (AB, J ) 11.2,
2H), 4.93 (m, 1H), 4.53 and 4.84 (AB, J ) 10.9, 2H), 4.60-
4.72 (m, 4H), 4.37-4.49 (m, 5H), 4.14-4.20 (m, 2H), 4.01 (m,
1H), 3.80 (dd, J ) 10.5, 3.0, 1H), 3.68 (dd, J ) 10.5, 6.2, 1H),
3.50-3.63 (m, 5H), 3.41 (m, 1H), 2.52 (m, 2H), 1.97 (s, 3H),
1.19-1.65 (m, 28H), 1.12 (d, J ) 6.2, 3H); 13C NMR (CDCl3,
75 MHz) δ 169.9, 168.2, 168.1, 155.4, 141.6, 138.9, 138.3, 138.2,
138.2, 138.1, 137.5, 136.8, 135.7, 130.1, 128.5, 128.4, 128.3,
128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.6, 127.5,
127.5, 127.0, 124.0, 121.8, 79.2, 78.9, 78.7, 77.1, 75.4, 75.2, 75.0,
74.8, 74.5, 74.0, 73.5, 73.4, 72.8, 70.4, 69.4, 69.0, 66.9, 35.8,
33.4, 31.2, 29.7, 29.5, 29.5, 29.4, 29.4, 25.2, 20.5, 19.6; MS (ESI)
1512 ([M + NH4]+), 1517 ([M + Na]+), 1533 ([M + K]+);
2-Ben zyloxy-6-{(16R)-[2-O-a cetyl-3,4,6-tr i-O-ben zyl-D-
m a n n on oyloxy]h ep t a d ecyl}b en zoic Acid Ben zyl E st er
(29). BF3‚OEt2 (300 µL, 2.289 mmol) was added to a solution
of compound 28 (576 mg, 0.489 mmol) in CH2Cl2 (20 mL) at
0 °C, and the mixture was stirred for 1.5 h while reaching
ambient temperature. After addition of aqueous NaHCO3/
NaCl (20 mL), the aqueous phase was extracted with ethyl
acetate (3 × 30 mL), the combined organic layers were dried
over Na2SO4, the solvents were removed in vacuo, and the
residue was chromatographed (hexane/ethyl acetate 4:1 f 2:1)
yielding 29 as a colorless syrup (430 mg, 83%): [R]20D +2.6° (c
11.9, CHCl3); IR 3544, 2926, 2854, 1734, 1454, 1267, 1107,
C
94H110O16 (1495.89) calcd C 75.48, H 7.41, found C 75.42, H
7.40.
Disa cch a r id e 34. Triflic anhydride (400 µL, 2.437 mmol)
was added to a solution of compound 32 (273 mg, 0.183 mmol)
in CH2Cl2 (8 mL) and pyridine (2 mL) at 0 °C. The mixture
was warmed to ambient temperature and stirred for 45 min.
The reaction mixture was quenched with aqueous NaHCO3/
NaCl (15 mL) and extracted with ethyl acetate (3 × 30 mL),
and the combined organic layers were dried over Na2SO4,
filtered, and evaporated. Excess pyridine was removed by
repeated azeotropic distillation with toluene. The residue was
then purified by flash chromatography (hexane/ethyl acetate
10:1 f 4:1) affording triflate 33 as a pale yellow syrup (226
mg, 78%) which was processed without delay. A solution of
this triflate (224 mg, 0.140 mmol) and Bu4NOAc (450 mg, 1.396
mmol) in toluene (10 mL) was placed in an ultrasound cleaning
bath (Brandelin Sonorex RK 514) for 16 h. Evaporation of the
solvent followed by flash chromatography (hexane/ethyl
acetate 4:1) gave compound 34 as a colorless syrup (205 mg,
95%): [R]20D -16.6° (c 6.6, CHCl3); IR 2926, 2854, 1743, 1454,
1371, 1266, 1237, 1107, 1066, 737, 698; 1H NMR (CDCl3, 300
MHz) δ 7.15-7.38 (m, 41H), 6.79 (d, J ) 7.7, 1H), 6.76 (d, J )
8.3, 1H), 5.64 (bd, J ) 3.2, 1H), 5.32 (s, 2H), 5.20 (d, J ) 5.0,
1H), 5.05 (s, 2H), 4.92 (m, 1H), 4.83 (A part of AB, J ) 10.9,
1H), 4.60-4.76 (m, 6H), 4.38-4.54 (m, 6H), 4.25 (m, 1H), 4.08
(m, 1H), 3.99 (m, 1H), 3.88 (dd, J ) 10.6, 2.9, 1H), 3.62-3.78
(m, 4H), 3.55 (dd, J ) 9.3, 3.2, 1H), 3.38 (m, 1H), 2.52 (m, 2H),
2.12 (s, 3H), 1.96 (s, 3H), 1.11 (d, J ) 6.3, 3H), 1.14-1.74 (m,
28H); 13C NMR (CDCl3, 75 MHz) δ 170.5, 169.7, 168.3, 168.2,
155.4, 141.6, 138.4, 138.3, 138.2, 137.7, 136.8, 135.7, 128.5,
128.4, 128.4, 128.4, 128.3, 128.2, 128.2, 128.1, 128.1, 128.0,
127.9, 127.7, 127.6, 127.5, 127.5, 127.4, 127.4, 127.0, 124.0,
121.8, 109.9, 98.3, 80.5, 79.2, 78.0, 75.5, 75.1, 74.5, 74.3, 73.3,
73.2, 73.0, 72.7, 71.4, 70.4, 70.2, 69.2, 68.3, 66.9, 35.8, 33.4,
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1065, 737, 698; H NMR (CDCl3, 300 MHz) δ 7.17-7.38 (m,
26H), 6.80 (d, J ) 7.8, 1H), 6.76 (d, J ) 8.3, 1H), 5.36 (d, J )
4.6, 1H), 5.32 (s, 2H), 5.06 (s, 2H), 4.93 (m, 1H), 4.72 (A part
of AB, J ) 11.5, 1H), 4.62-4.66 (m, 2H), 4.45-4.54 (m, 3H),
4.14 (m, 1H), 4.02 (m, 1H), 3.81 (dd, J ) 7.4, 4.8, 1H), 3.58-
3.68 (m, 2H), 2.58 (bs, 1H, OH), 2.52 (m, 2H), 2.03 (s, 3H),
1.14 (d, J ) 6.3, 3H), 1.09-1.73 (bs, 28H); 13C NMR (CDCl3,
75 MHz) δ 169.8, 168.2, 168.1, 155.4, 141.6, 138.0, 137.8, 137.7,
136.8, 135.7, 130.1, 128.5, 128.4, 128.4, 128.4, 128.3, 128.2,
128.1, 128.0, 128.0, 127.8, 127.7, 127.7, 127.0, 124.0, 121.8,
109.9, 78.9, 78.4, 74.3, 74.1, 73.4, 72.8, 72.6, 70.8, 70.4, 66.9,
35.7, 33.4, 31.2, 29.6, 29.6, 29.5, 29.5, 29.4, 25.1, 20.6, 19.5;
MS (ESI) 1080 ([M + NH4]+), 1085 ([M + Na]+), 1101 ([M +
K]+); C67H82O11 (1063.37) calcd C 75.68, H 7.77, found C 75.71,
H 7.78.
Disa cch a r id e 31. A mixture of alcohol 29 (200 mg, 0.19
mmol), van Boeckel catalyst (420 mg),22 and powdered mole-
cular sieves (3 Å) in CH2Cl2 (5 mL) was stirred for 10 min at
rt. After the solution was cooled to -5 °C, a solution of
bromide 16 (300 mg, 0.51 mmol) in CH2Cl2 (3 mL) was slowly
added and stirring was continued at that temperature for 45
min. The catalyst and the molecular sieves were filtered off
and thoroughly rinsed with ethyl acetate. Evaporation of the
combined filtrates followed by flash chromatography (hexane/
ethyl acetate 4:1) of the remaining residue afforded glycoside
31 (218 mg, 74%) as a colorless syrup: [R]25 +10.8° (c 6.2,
D
CHCl3); IR 2926, 2854, 1743, 1454, 1369, 1269, 1266, 1063,