Voight et al.
1H), 2.18 (s, 3H), 2.17 (dd, J ) 15, 2.5 Hz, 1H), 2.16 (s, 3H),
2.08 (s, 3H), 2.05 (s, 3H); 13C NMR (CDCl3) δ 170.5 (C), 170.0
(C), 169.8 (C), 169.6 (C), 149.4 (C), 148.7 (C), 131.7 (C), 117.6
(CH), 110.7 (CH), 108.2 (CH), 107.6 (C), 77.2 (CH), 74.1 (CH),
71.1 (CH), 69.4 (CH), 68.2 (CH), 62.3 (CH2), 56.0 (CH3), 55.9
(CH3), 37.4 (CH2), 21.2 (CH3), 21.0 (CH3), 20.9 (CH3), 20.7
-6.8 (c 0.28, CHCl3); HRMS (FAB) calcd for C21H30O14Na (M
+ Na+) 529.1533, found 529.1555.
P r ep a r a tion of Com p ou n d 45. Inverted tetraacetate 40
(680 mg, 1.33 mmol) was dissolved in MeOH (13 mL) and
sodium methoxide (0.5 M solution in MeOH, 0.67 mL, 0.33
mmol) was added. After the solution was stirred at rt for 4 h,
concentration and FCC (0-10% MeOH/EtOAc, gradient elu-
tion) gave pure 45 (452 mg, 99%) as a white solid that could
be recrystallized from MeOH/EtOAc to give analytically pure
clear needles (mp 116-117 °C). 1H NMR (CD3OD) δ 7.17 (d, J
) 2 Hz, 1H), 7.12 (dd, J ) 8.5, 2 Hz, 1H), 6.93 (d, J ) 8.5 Hz,
1H), 4.63 (ddd, J ) 1.5, 1, 0.5 Hz, 1H), 4.37 (dd, J ) 9.5, 1 Hz,
1H), 3.93 (dddd, J ) 5.5, 3.5, 1.5, 1.5 Hz, 1H), 3.84 (s, 3H),
3.83 (s, 3H), 3.77 (dd, J ) 11.5, 3 Hz, 1H), 3.67 (ddd, J ) 3.5,
1, 0.5 Hz, 1H), 3.57 (dd, J ) 11.5, 6 Hz, 1H), 3.38 (ddd, J )
9.5, 6, 3 Hz, 1H), 2.36 (dd, J ) 14.5, 5.5 Hz, 1H), 1.99 (ddd, J
) 14.5, 1.5, 0.5 Hz, 1H); 13C NMR (CD3OD) δ 150.7 (C), 150.2
(C), 135.5 (C), 119.1 (CH), 112.5 (CH), 110.6 (CH), 108.9 (C),
81.1 (CH), 77.3 (CH), 74.1 (CH), 72.0 (CH), 70.5 (CH), 64.7
(CH2), 56.64 (CH3), 56.59 (CH3), 40.6 (CH2); IR (thin film) 3291,
(CH3); IR (thin film) 2968, 1743, 1740, 1734 cm-1; [R]24 +51
D
(c 1.1, CDCl3); HRMS (FAB) calcd for C24H30O12Na (M + Na+)
533.1635, found 533.1622.
P r ep a r a tion of Com p ou n d 41. Inverted tetraacetate 40
(223 mg, 0.437 mmol) was dissolved in MeOH (10 mL) and
concentrated sulfuric acid (1 drop) was added at 0 °C. After
being stirred at 0 °C for 3 h, the clear solution was poured
into saturated aqueous sodium bicarbonate (15 mL), CH2Cl2
(30 mL) was added, layers separated, and the aqueous phase
was extracted with CH2Cl2 (2 × 30 mL). The combined organics
were dried (MgSO4), concentrated, and dissolved in CH2Cl2 (10
mL). Et3N (0.488 mL, 3.50 mmol), acetic anhydride (0.165 mL,
1.75 mmol), and 4-dimethylamino pyridine (5.3 mg, 0.044
mmol) were then added at rt, and the reaction was stirred 2
h. After the mixture was poured into water (15 mL) and CH2-
Cl2 (20 mL) added, the separated aqueous phase was extracted
with CH2Cl2 (2 × 20 mL). The combined organics were dried
(MgSO4) and concentrated, and FCC (20-50% Et2O/hexanes,
gradient elution) gave 40 (37 mg, ∼90% pure by 1H NMR) and
pure 41 (229 mg, 90%, 100% based on recovered 40) as white
flakes (mp 50-51 °C). 1H NMR (CDCl3) δ 7.04 (dd, J ) 8, 2
Hz, 1H), 6.94 (d, J ) 2 Hz, 1H), 6.87 (d, J ) 8 Hz, 1H), 5.48
(dd, J ) 6, 2 Hz, 1H), 5.43 (ddd, J ) 11.5, 9.5, 5.5 Hz, 1H),
5.38 (td, J ) 6, 2.5 Hz, 1H), 4.95 (t, J ) 9.5 Hz, 1H), 4.54 (dd,
J ) 12.5, 2.5 Hz, 1H), 4.22 (dd, J ) 12.5, 6 Hz, 1H), 4.19 (dd,
J ) 9.5, 2 Hz, 1H), 3.90 (s, 3H), 3.89 (s, 3H), 2.95 (s, 3H), 2.54
(dd, J ) 13, 5.5 Hz, 1H), 2.16 (s, 3H), 2.07 (s, 3H), 2.06 (s,
3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.76 (dd, J ) 13, 11.5 Hz, 1H);
13C NMR (CDCl3) δ 170.6 (C), 170.3 (C), 170.04 (C), 169.97
(C), 169.9 (C), 149.0 (C), 148.9 (C), 131.9 (C), 118.2 (CH), 110.8
(CH), 108.8 (CH), 101.2 (C), 70.2 (CH), 70.1 (CH), 69.2 (CH),
68.3 (CH), 67.6 (CH), 62.0 (CH2), 55.9 (CH3 × 2), 49.4 (CH3),
42.0 (CH2), 21.0 (CH3), 20.9 (CH3), 20.8 (CH3), 20.7 (CH3), 20.6
(CH3); IR (thin film) 2940, 1751, 1734 cm-1; [R]24D +13 (c 0.30,
CHCl3); HRMS (FAB) calcd for C27H36O14Na (M + Na+)
607.2003, found 607.2033.
2916 cm-1; [R]22 +31 (c 0.87, MeOH); HRMS (ESI) calcd for
D
C
16H22O8Na (M + Na+) 365.1212, found 365.1206.
P r ep a r a tion of Com p ou n d 46. Tetraol 45 (20.4 mg,
0.0596 mmol) was dissolved in DMF (1.2 mL) and cooled to 0
°C. Imidazole (12.2 mg, 0.179 mmol) and 1,3-dichlorotetrai-
sopropyl disiloxane (29 µL, 0.089 mmol) were then added, and
the reaction was slowly warmed rt over 2.5 h. MeOH (2 mL)
was added, stirring was continued for 5 min, and the reaction
was poured into water (20 mL) and Et2O (50 mL). The aq layer
was extracted with Et2O (3 × 20 mL), the organics were dried
(MgSO4) and concentrated, and FCC (50-100% Et2O/hexanes,
gradient elution) gave pure 46 (31.4 mg, 90%) as a clear oil
that could be recrystallized from Et2O/hexanes to give a white
1
solid (mp 87-89 °C). H NMR (CD3OD) δ 7.17 (d, J ) 2 Hz,
1H), 7.13 (dd, J ) 8.5, 2 Hz, 1H), 6.96 (d, J ) 8.5 Hz, 1H),
4.70 (br s, 1H), 4.28 (br d, J ) 8 Hz, 1H), 4.10-4.21 (m, 1H),
3.95 (dddd, J ) 5.5, 3.5, 1.5, 1.5 Hz, 1H), 3.86 (s, 6H), 3.63-
3.80 (m, 2H), 3.63 (br s, 1H), 2.39 (dd, J ) 14.5, 5.5 Hz, 1H),
1.99 (br d, J ) 14.5 Hz, 1H); 13C NMR (CD3OD) δ 150.8 (C),
150.3 (C), 135.3 (C), 119.1 (CH), 112.6 (CH), 110.6 (CH), 109.2
(C), 81.0 (CH), 77.7 (CH), 77.3 (CH), 72.0 (CH), 70.4 (CH), 68.5
(CH2), 56.7 (CH3), 56.5 (CH3), 40.3 (CH2), 17.8-18.2 (CH3 ×
8), 14.7 (CH), 14.1 (CH), 13.92 (CH), 13.85 (CH); IR (thin film)
3294, 2941 cm-1; [R]22D -10 (c 0.59, CHCl3); HRMS (ESI) calcd
for C28H48O9Si2Na (M + Na+) 607.2735, found 607.2760.
P r ep a r a tion of Com p ou n d 42. Aryl methyl glycoside 41
(62 mg, 0.106 mmol) was dissolved in 2:2:3 carbon tetrachloride/
acetonitrile/water (2.1 mL). Sodium periodate (272 mg, 1.27
mmol) and ruthenium(III)chloride trihydrate (1.1 mg, 0.0053
mmol) were then added, and the reaction was stirred at rt for
6 h. Ethyl acetate (50 mL), saturated aqueous ammonium
chloride (10 mL), and water (10 mL) were then added, the
organic layer was separated, and the aqueous layer was
extracted with ethyl acetate (4 × 20 mL). The combined
organics were dried (MgSO4), concentrated, and dissolved in
PhH (1.6 mL) and MeOH (0.5 mL). Trimethylsilyl diaz-
omethane (2 M in hexanes, 0.11 mL, 0.21 mmol) was added
and the reaction was stirred at rt for 2 h. Glacial acetic acid
(0.5 mL) was then added and the yellow solution was stirred
at rt an additional 30 min and concentrated, and FCC (25-
50% Et2O/hexanes, gradient elution) gave pure 42 (45 mg,
84%), which could be recrystallized from Et2O/hexanes to give
analytically pure clear square plates (mp 115-116 °C). 1H
NMR (CDCl3) δ 5.42 (dd, J ) 5.5, 2.5 Hz, 1H), 5.32 (ddd, J )
11.5, 10, 5 Hz, 1H), 5.31 (ddd, J ) 6.5, 5.5, 2 Hz, 1H), 4.90 (t,
J ) 10 Hz, 1H), 4.71 (dd, J ) 12.5, 2.5 Hz, 1H), 4.15 (dd, J )
12.5, 6.5 Hz, 1H), 4.06 (dd, J ) 10, 2 Hz, 1H), 3.82 (s, 3H),
3.26 (s, 3H), 2.52 (dd, J ) 13, 5 Hz, 1H), 2.12 (s, 3H), 2.08 (s,
3H), 2.04 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H), 1.84 (dd, J ) 13,
11.5 Hz, 1H); 13C NMR (CDCl3) δ 170.6 (C), 170.2 (C), 170.00
(C), 169.92 (C), 169.8 (C), 167.1 (C), 98.7 (C), 70.8 (CH), 69.9
(CH), 69.1 (CH), 67.8 (CH), 67.4 (CH), 62.0 (CH2), 52.7 (CH3),
51.3 (CH3), 36.9 (CH2), 21.0 (CH3), 20.8 (CH3), 20.72 (CH3),
P r ep a r a tion of Com p ou n d 47. Diol 46 (1.50 g, 2.56 mmol)
was dissolved in CH2Cl2 (27 mL), and Et3N (1.51 mL, 10.8
mmol), TsCl (1.03 g, 5.41 mmol), and 4-dimethylamino pyri-
dine (33 mg, 0.27 mmol) were added. After the mixture was
stirred for 2 d at rt, NaOMe (0.5 M in MeOH, 22 mL, 10.8
mmol) was added and the reaction was stirred 30 min. Water
(100 mL) was added, the aq layer was extracted with CH2Cl2
(4 × 50 mL), the combined organics were dried (Na2SO4) and
concentrated, and FCC (10-20% Et2O/hexanes, gradient elu-
tion) gave pure 47 (1.07 g, 74%) as a clear oil. 1H NMR (CDCl3)
δ 7.05 (dd, J ) 8, 2 Hz, 1H), 7.01 (d, J ) 2 Hz, 1H), 6.84 (d, J
) 8 Hz, 1H), 5.05 (d, J ) 5 Hz, 1H), 4.00-4.16 (m, 2H), 3.89
(s, 3H), 3.88 (s, 3H), 3.59-3.75 (m, 3H), 3.36 (dd, J ) 4, 3 Hz,
1H), 2.37 (d, J ) 15.5 Hz, 1H), 2.12 (dd, J ) 15.5, 4 Hz, 1H),
0.80-1.11 (m, 28H); 13C (CDCl3) δ 149.1 (C), 148.7 (C), 133.5
(C), 117.3 (CH), 110.7 (CH), 108.2 (CH), 105.4 (C), 75.9 (CH),
75.4 (CH), 74.9 (CH), 67.1 (CH2), 55.9 (CH3), 55.8 (CH3), 52.1
(CH), 49.1 (CH), 36.4 (CH2), 17.2-17.5 (CH3 × 8), 13.2 (CH),
12.6 (CH), 12.52 (CH), 12.45 (CH); IR (thin film) 2945 cm-1
;
[R]22 +5.5 (c 0.51, CHCl3); HRMS (ESI) calcd for C28H46O8-
D
Si2Na (M + Na+) 589.2629, found 589.2657.
P r ep a r a tion of Com p ou n d 48. Epoxide 47 (610 mg, 1.08
mmol) was dissolved in DMF (11 mL). Sodium azide (741 mg,
11.4 mmol) and magnesium sulfate (274 mg, 2.28 mmol) were
added and the reaction was heated at 90-95 °C for 20 h. The
reaction was poured into 50% saturated sodium bicarbonate,
extracted with Et2O (5 × 75 mL), dried (MgSO4), and concen-
20.67 (CH3), 20.6 (CH3); IR (thin film) 2956, 1748 cm-1; [R]24
D
8498 J . Org. Chem., Vol. 67, No. 24, 2002