P. Deslongchamps et al.
FULL PAPERS
NaHCO3 was added to quench the reaction. The mixture was extracted
with Et2O. The combined organic extracts were washed with brine, dried
over Na2SO4, and evaporated. The residue was purified by flash chroma-
tography (EtOAc/hexane=1:9 to 3:7) to yield 4-methoxybenzyl ether 50
(1.11 g, 76%). ½aꢁ2D0 =+16.87 (c=2.68, CHCl3); IR (NaCl): n˜ =2956.3,
1738.2 (C=O), 1711.0 (C=O), 1611.3, 1513.3, 1245.8, 1111.7, 1040.2, 822.9,
ꢀ788C. After the mixture was stirred at ꢀ788C for 2 h, it was poured
into saturated NH4Cl solution (8 mL), extracted with EtOAc, washed
with brine, and dried over Na2SO4. Purification of the residue by flash
chromatography (EtOAc/hexane=1:1) gave triol 54 (61.6 mg, 97%) as
an oil. ½aꢁ2D0 =+10.19 (c=2.11, CHCl3); IR (NaCl): n˜ =3491.9 (OH),
3189.2 (OH), 2930.3, 1697.6 (C=O), 1611.3, 1512.5, 1427.3, 1250.0, 1111.3,
1
1082.3, 822.4, 701.4 cmꢀ1; H NMR (CDCl3, 300 MHz): d=7.69–7.66 (4H,
1
702.8 cmꢀ1; H NMR (CDCl3, 300 MHz): d=7.68–7.61 (4H, m), 7.44–7.33
m), 7.45–7.32 (11H, m), 7.20 (2H, d, J=8.64 Hz, MeOPh-), 6.86 (2H, d,
J=8.64 Hz, MeOPh-), 4.52 (1H, d, J=11.63 Hz, MeOC6H4CHaHb), 4.29
(1H, d, J=11.63 Hz, MeOC6H4CHaHb), 4.18–4.10 (1H, m), 4.09 (1H, s),
3.80 (3H, s, CH3OPh), 3.86–3.60 (4H, m), 3.55 (1H, d, J=10.03 Hz), 2.86
(1H, d, J=13.24 Hz, 8-H), 2.67–2.48 (2H, m), 1.94–1.56 (10H, m), 1.37–
1.14 (5H, m), 1.06 (9H, s, tBu), 0.93 (3H, s, 13-CH3), 0.93–0.85 (1H, m),
0.22 (3H, s, SiMe2), 0.21 ppm (3H, s, SiMe2); 13C NMR (CDCl3,
75 MHz): d=218.31, 159.30, 137.13, 135.72, 135.62, 135.52, 134.33, 134.19,
133.75, 129.36, 129.78, 129.70, 129.44, 129.15, 127.83, 127.54, 113.75, 83.57,
75.39, 72.93, 66.93, 66.29, 65.79, 55.24, 51.31, 51.12, 49.28, 47.92, 46.68,
44.68, 42.70, 32.42, 32.18, 31.05, 27.49, 26.95, 24.34, 19.27, 17.36, 15.40,
ꢀ5.30, ꢀ5.62 ppm; EIMS: m/z (%): 842 [M+-H2O], 824 [M+-2H2O], 803
[M+-C4H9], 785, 477, 199, 121; HREIMS: m/z (%) calcd for C52H66O6Si2:
842.4398 [M-H2O]; found: 842.4393ꢂ0.0025.
(11H, m), 7.14 (2H, d, J=8.67 Hz, MeOPh-), 6.83 (2H, d, J=8.67 Hz,
MeOPh-), 5.27 (1H, dd, J=3.70, 10.03 Hz, AcOCH), 4.42 (1H, d, J=
11.84 Hz, MeOPhCH2), 4.22 (1H, d, J=11.84 Hz, MeOPhCH2), 3.78
(3H, s, CH3OPh), 3.76–3.59 (4H, m, MPMOCH2 and CH2OTBDPS),
2.93 (1H, m), 2.60 (1H, m), 2.50–1.91 (10H, m), 1.88 (3H, s, OAc), 1.71–
1.21 (6H, m), 1.05 (9H, s, tBu), 0.84 (3H, s, 13-CH3), 0.20 ppm (6H, s,
SiMe2); 13C NMR (CDCl3, 75 MHz): d=221.80, 211.31, 210.53, 170.17,
159.29, 136.38, 135.52, 133.74, 133.31, 133.23, 129.82, 129.66, 129.41,
127.95, 127.84, 127.78, 113.74, 72.89, 70.74, 69.38, 64.57, 55.22, 54.66,
49.26, 43.98, 43.22, 41.99, 40.47, 39.84, 38.84, 37.73, 36.39, 27.36, 26.94,
22.26, 21.62, 21.22, 19.27, 18.26, ꢀ4.90, ꢀ5.01 ppm; EIMS: m/z (%): 882
[M+-H2O], 843 [M+-C4H9], 686, 633, 199, 135; HREIMS: m/z (%) calcd
for C54H66O7Si2: 882.4347 [M-H2O]; found: 882.4355ꢂ0.0026.
52: Potassium bis(trimethylsilyl)amide (0.5m in toluene, 0.217 mL,
0.110 mmol) was added to a stirring solution of tricycle 51 (0.4900 g,
0.540 mmol) in dry THF (50 mL) at ꢀ788C. The reaction mixture was
then stirred at 638C for about 10 min, then cooled to 08C, filtered
through a pad of silica gel and rinsed with EtOAc. After concentration,
purification of the residue was achieved by flash chromatography
(EtOAc/hexane=1:3) to give tetracycle 52 (0.407 g, 83%) as an oil.
½aꢁ2D0 =ꢀ38.99 (c=4.25, CHCl3); IR (NaCl): n˜ =3524.7 (OH), 2955.2,
1744.0 (C=O), 1698.5 (C=O), 1513.8, 1427.5, 1232.5, 1111.0, 1035.2, 816.1,
57: PMB ether 54 (0.3667 g, 0.426 mmol) was dissolved in CH2Cl2
(40 mL) at RT and then powder 4 ꢄ molecular sieves were added. After
stirring at RT for 1 h, DDQ (0.3866 g, 1.703 mmol) was added. The mix-
ture was stirred at RT for 39 h, and filtered through a pad of silica gel.
The filtrate was washed with an aqueous solution of NaHCO3, then dried
with MgSO4 and concentrated. Further purification of the residue by
flash chromatography (EtOAc/hexane=1:4) gave ortho-ester 57
(0.3073 g, 84%) and a mixture of acetals 55 and 56 (0.0406 g, 11%),
which can be converted to orthoester 57 with the above conditions.
½aꢁ2D0 =+44.07 (c=1.97, CHCl3); IR (NaCl): n˜ =3493.8 (OH), 2932.4,
1699.4 (C=O), 1612.0, 1514.9, 1427.5, 1298.0, 1249.1, 1112.1, 832.1,
1
702.2 cmꢀ1; H NMR (CDCl3, 300 MHz): d=7.66–7.62 (4H, m), 7.45–7.33
(11H, m), 7.22 (2H, d, J=8.68 Hz, MeOPh-), 6.86 (2H, d, J=8.68 Hz,
MeOPh-), 5.01 (1H, m), 4.47 (2H, s, MeOC6H4CH2), 3.88–3.73 (3H, m),
3.80 (3H, s, CH3OPh), 3.68–3.62 (1H, m), 3.53 (1H, s), 2.98–2.89 (3H,
m), 2.69–2.54 (2H, m), 2.34–2.29 (1H, m), 2.11–1.92 (5H, m), 1.86 (3H, s,
OAc), 1.80–1.55 (4H, m), 1.22–1.15 (2H, m), 1.03 (9H, s, tBu), 0.93 (3H,
s, 13-CH3), 0.27 (3H, s, SiMe2), 0.26 ppm (3H, s, SiMe2); 13C NMR
(CDCl3, 75 MHz): d=213.34, 210.94, 169.80, 159.22, 137.01, 135.56,
134.13, 133.72, 129.87, 129.48, 129.33, 127.92, 127.54, 113.75, 82.36, 73.57,
69.20, 68.56, 66.65, 55.24, 53.53, 51.84, 51.04, 47.19, 44.73, 43.90, 43.23,
40.62, 37.96, 32.29, 28.77, 26.88, 24.63, 24.23, 20.75, 19.23, 15.32, ꢀ3.54,
ꢀ3.84 ppm; EIMS: m/z (%): 882 [M+-H2O], 843 (M+-C4H9], 686, 199,
135, 121; HREIMS: m/z (%) calcd for C54H66O7Si2: 882.4347 [M-H2O];
found: 882.4355ꢂ0.0026.
701.2 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=7.72–7.67 (4H, m), 7.56
;
(2H, d, J=8.92 Hz, MeOPh-), 7.50–7.36 (11H, m), , 6.88 (2H, d, J=
8.92 Hz, MeOPh-), 4.30–4.19 (2H, m), 4.15–4.06 (2H, m), 4.01 (1H, s,
OH), 3.89–3.84 (1H, m), 3.81 (3H, s, CH3OPh), 3.74–3.69 (1H, m), 2.65
(1H, dd, J=14.50, 16.06 Hz, 9-H), 2.49 (1H, d, J=13.75 Hz, H-8), 2.12–
1.77 (9H, m), 1.71–1.48 (4H, m), 1.39–1.34 (1H, m), 1.08 (3H, s, 13-
CH3), 1.07 (9H, s, tBu), 1.00–0.86 (1H, m), 0.32 ppm (6H, s, SiMe2);
13C NMR (CDCl3, 75 MHz): d=216.25, 159.86, 136.64, 135.62, 134.23,
134.15, 133.78, 133.49, 129.48, 129.38, 127.98, 127.89, 127.58, 127.49,
127.04, 127.00, 126.96, 113.21, 110.27, 83.51, 79.16, 68.02, 66.78, 65.34,
55.32, 51.62, 50.25, 48.64, 47.15, 43.90, 43.39, 36.58, 33.73, 33.11, 30.84,
28.64, 26.93, 24.44, 19.27, 17.38, 15.98, ꢀ5.09, ꢀ5.44 ppm; EIMS: m/z
(%): 838 [M+-H2O], 799 [M+-C4H9], 781, 199, 135; HREIMS: m/z (%)
calcd for C52H62O6Si2: 838.4085 [M-H2O]; found: 838.4076ꢂ0.0025.
53: The acetate 52 (0.4468 g, 0.496 mmol) was dissolved in THF (5.5 mL)
and MeOH (5.5 mL). Powder K2CO3 (0.0982 g, 0.712 mmol) was added
and the reaction mixture was stirred at RT overnight. EtOAc was added
to dilute the reaction. It was filtered through a pad of silica gel. Purifica-
tion of the residue by flash chromatography (EtOAc/hexane=1:2) gave
the corresponding alcohol 53 (0.4165 g, 98%) as an oil. ½aꢁ2D0 =+58.66
(c=2.61, CHCl3); IR (NaCl): n˜ =3500.4 (OH), 2954.6, 1694.6 (C=O),
59:
tert-Butyldimethylsilyl
trifluoromethanesulfonate
(0.81 mL,
3.54 mmol) was added dropwise to
a
mixture of Et3N (1.23 mL,
8.82 mmol) and CH2Cl2 (0.5 mL) at 08C. Then a solution of ketone 57
(0.2014 g, 0.235 mmol) in CH2Cl2 (1.5 mL) was added drop wise. It was
warmed up to RT and stirred for 4.5 h. iPrOH (0.36 mL, 4.64 mmol) was
added to quench the reaction at 08C. The mixture was filtered through a
pad of silica gel. Further purification of the residue by flash chromatogra-
phy (EtOAc/hexane=1:6) gave the TBS enol ether 59 (0.1545 g, 90%).
Some starting material (0.0504 g, conversion 75%) was also recovered.
½aꢁ2D0 =+34.9 (c=1.19, CHCl3); IR (NaCl): n˜ =3521.4 (OH), 2954.2,
1611.8, 1513.6, 1427.4, 1249.7, 1111.2, 1081.8, 820.5, 702.0 cmꢀ1 1H NMR
;
(CDCl3, 300 MHz): d=7.69–7.66 (4H, m), 7.44–7.35 (11H, m), 7.22 (2H,
d, J=8.60 Hz, MeOPh-), 6.89 (2H, d, J=8.60 Hz, MeOPh-), 4.54 (1H, d,
J=11.64 Hz,
MeOC6H4CHaHb),
4.36
(1H,
d,
J=11.64 Hz,
MeOC6H4CHaHb), 3.95 (1H, s), 3.92–3.75 (4H, m), 3.82 (3H, s,
CH3OPh), 3.71–3.65 (1H, m), 3.05 (1H, d, J=6.85 Hz, 8-H), 2.76–2.81
(1H, m), 2.67–2.51 (2H, m), 2.41–2.19 (3H, m), 2.02–1.66 (8H, m), 1.40–
1.28 (3H, m), 1.06 (9H, s, tBu), 0.91 (3H, s, 13-CH3), 0.26 ppm (6H, s,
SiMe2); 13C NMR (CDCl3, 75 MHz): d=216.65, 215.98, 159.54, 135.87,
135.72, 135.62, 135.56, 134.35, 134.24, 133.73, 129.84, 129.76, 129.57,
129.43, 128.96, 128.03, 127.53, 113.92, 83.70, 73.11, 68.11, 66.95, 66.28,
56.08, 55.26, 51.38, 50.71, 48.06, 46.98, 43.37, 41.16, 40.41, 37.00, 32.62,
27.89, 26.93, 24.38, 22.59, 19.26, 15.44, ꢀ5.23, ꢀ5.58 ppm; EIMS: m/z (%)
840 [M+-H2O], 822 [M+-2H2O], 801 [M+-C4H9], 783, 199, 135, 121;
HREIMS: m/z (%) calcd for C52H64O6Si2: 840.4241 [M-H2O]; found:
840.4268ꢂ0.0025.
1
1673.0, 1613.7, 1515.6, 1249.1, 1111.9, 831.8, 701.0 cmꢀ1; H NMR (CDCl3,
300 MHz): d=7.70–7.65 (4H, m), 7.54–7.49 (4H, m), 7.44–7.33 (9H, m),
6.85 (2H, d, J=8.88 Hz, MeOPh-), 4.42 (1H, dd, J=1.97, 4.86 Hz, 6-H),
4.26 (1H, dt, J=2.75, 10.88 Hz, 11-H), 4.05 (1H, dd, J=4.04, 11.96 Hz, 1-
H), 3.98 (1H, s, OH), 3.87–3.80 (2H, m), 3.79 (3H, s, CH3OPh), 3.78–
3.67 (2H, m), 2.40 (1H, d, J=10.83, 8-H), 1.98–1.55 (10H, m), 1.45–1.19
(4H, m), 1.08 (3H, s, 13-CH3), 1.05 (9H, s, tBu), 0.93 (9H, s, tBu), 0.32
(3H, s, tBuSiMe2), 0.31 (3H, s, tBuSiMe2), 0.19 (3H, s, PhSiMe2),
0.18 ppm (3H, s, PhSiMe2); 13C NMR (CDCl3, 75 MHz): d=159.76,
149.09, 137.24, 135.62, 134.29, 134.26, 133.79, 133.34, 129.41, 129.38,
129.27, 127.82, 127.50, 126.73, 126.69, 113.22, 111.43, 107.08, 84.81, 78.65,
70.63, 65.88, 65.06, 55.31, 52.86, 49.01, 48.59, 47.17, 43.59, 36.82, 34.37,
33.32, 28.65, 26.93, 26.89, 26.03, 25.50, 25.02, 19.25, 18.21, 18.07, 16.43,
54: NaBH4 (1.67 mg, 0.0441 mmol) in EtOH (0.8 mL) was added slowly
to a solution of ketone 53 (63.3 mg, 0.0737 mmol) in EtOH (2 mL) at
736
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2009, 4, 725 – 741