Chain-Extended Analogues of Salacinol and Blintol
2×-OMe), 3.61 (1H, dd, J1a,1b ) 12.9, J1b,2 ) 3.2 Hz, H-1b). 13C
NMR (CDCl3): δ 159.6-114.0 (18C, Ar), 103.9 (Ph-CH-), 80.1
(C-5), 79.3 (C-3), 77.3 (C-4), 76.7 (C-2), 73.1, 72.0 (2×-Ph-CH2-),
61.4 (C-6), 58.2 (C-1), 55.5 (2C, 2×-OMe). MALDI: m/e 579.6
(M+ + Na). Anal. Calcd for C29H32O9S: C, 62.58; H, 5.79.
Found: C, 62.80; H, 6.08.
(C-3), 76.8 (C-2), 70.1 (C-4′, C-4), 68.8 (C-5′), 66.1 (C-2′), 62.9
(C-6′), 59.2 (C-5), 50.8 (C-1′), 47.9 (C-1). MALDI: m/e 395.36
(M+ + H), 417.58 (M+ + Na). HRMS calcd for C11H22O11S2 (M
- H): 393.05119. Found: 393.05215.
2,3,5-Tri-O-p-methoxybenzyl-1,4-dideoxy-1,4-[[(2S,3S,4R,5R)-
4,6-O-benzylidene-2,5-di-O-p-methoxybenzyl-3-(sulfooxy)hexyl]-
(R/S)-epi-seleniumylidene]-D-arabinitol Inner Salt (20 and 21).
To HFIP (3 mL) were added 1,4-dideoxy-2,3,5-tri-O-p-methoxy-
benzyl-1,4-anhydro-4-seleno-D-arabinitol 15 (254 mg, 0.45 mmol),
4,6-O-benzylidene-2,5-O-di-p-methoxybenzyl-D-mannitol-1,3-cy-
clic sulfate (13) (318 mg, 0.55 mmol), and anhydrous K2CO3 (40
mg). The mixture was stirred in a sealed tube at 65-70 °C for 36
h. The solvent was removed under reduced pressure, and the residue
was purified by flash column chromatography (3:1 hexanes:EtOAc
and then 15:1 EtOAc:MeOH) to give 20 (286 mg, 56%) and 21
4,6-O-Benzylidene-2,5-di-O-p-methoxybenzyl-D-mannitol 1,3-
Cyclic Sulfate (13). To a solution of compound 18 (2.58 g, 4.63
mmol) in a mixture of CH3CN:CCl4 (100 mL) were added sodium
periodate (1.48 g, 6.95 mmol) and RuCl3 (100 mg), followed by
H2O (20 mL). The mixture was then stirred for 2 h at rt. The
reaction mixture was filtered through a silica bed and washed
repeatedly with EtOAc. The volatile solvents were removed, and
the aqueous solution was extracted with EtOAc (2 × 100 mL).
The combined organic layer was washed with saturated NaCl, dried
over Na2SO4, and evaporated under diminished pressure. The
residue was purified by flash column chromatography to give 13
(122 mg, 23%) in a 5:2 ratio as white amorphous solids. Data for
1
trans isomer (20): [R]23 ) -19.5° (c ) 0.4, CH2Cl2). H NMR
D
as a white solid (2.30 g, 86%). mp 98 °C; [R]23 ) -44.6° (c )
(d6-acetone): δ 7.45-6.79 (25H, Ar-H), 5.21 (1H, s, Ph-CH-),
4.83 (1H, br d, J3′,2′ ) 8.9 Hz, H-3′), 4.81-4.39 (10H, 5×-MeO-
Ph-CH2-), 4.73 (1H, br dd, H-2), 4.55 (1H, br dd, H-3), 4.30-
4.19 (4H, m, H2-1′, H-2′, H-6a′), 4.13 (1H, m, H-5′), 4.09 (1H, br
d, J1a,1b ) 13.1, H-1a), 4.04 (1H, m, H-4), 3.84-3.63 (15H, 5×-
OMe), 3.81 (1H, m, H-4′), 3.79 (1H, m, H-5a), 3.72 (1H, m, H-1b),
3.71 (1H, dd, H-5b), 3.46 (1H, dd, H-6b′). 13C NMR (d6-acetone):
δ 159.6-113.2 (36C, Ar), 100.2 (Ph-CH-), 84.4 (C-3), 82.4 (C-
2), 77.9 (C-4′), 73.0 (C-3′), 72.4 (C-2′), 72.8, 72.6, 71.5, 71.4, 71.3
(5×-MeO-Ph-CH2-), 69.8 (C-6′), 67.4 (C-5′), 67.3 (C-5), 64.8
(C-4). 54.7 (5×-OMe), 50.0 (C-1′), 45.8 (C-1). MALDI: m/e
1131.51 (M+ + H), 1051.74 (M+ + H - SO3). Anal. Calcd for
C58H66O16SSe: C, 61.64; H, 5.89. Found: C, 61.31; H, 5.66. Data
for cis isomer (21): [R]23D ) -15.7° (c ) 0.1, CH2Cl2). 1H NMR
(d6-acetone): δ 7.31-6.81 (25H, Ar-H), 5.30 (1H, s, Ph-CH-),
4.86 (1H, br d, J3′,2′ ) 9.0 Hz, H-3′), 4.82-4.45 (10H, 5×-MeO-
Ph-CH2-), 4.74 (1H, br s, H-2), 4.68 (1H, br s, H-3), 4.41 (1H,
m, H-4), 4.29 (2H, m, H-2′, H-6a′), 4.21 (1H, dd, J5a,5b ) 9.9, J5a,4
) 5.4 Hz, H-5a), 4.18 (1H, m, H-5′), 4.06 (2H, m, H2-1), 4.00
(1H, dd, J5b,4 ) 9.4 Hz, H-5b), 3.83 (1H, m, H-4′), 3.80-3.65 (15H,
5×-OMe), 3.63 (1H, m, H-1a), 3.56 (1H, br d, J1b,1a ) 12.9, H-1b),
3.48 (1H, dd, J6b′,6a′ ) 10.4, J6b′,5′ ) 10.2 Hz, H-6b′). 13C NMR
(d6-acetone): δ 159.8-114.0 (36C, Ar), 100.6 (Ph-CH-), 83.2
(C-2), 82.6 (C-3), 77.8 (C-4′), 73.1 (C-3′), 72.8 (C-2′), 72.7, 72.1,
71.6, 71.2, 71.2 (5×-MeO-Ph-CH2-), 69.8 (C-6′), 67.2 (C-5′),
65.6 (C-5), 58.4 (C-4), 54.8, 54.7 (5×-OMe), 42.3 (C-1), 41.0 (C-
1′). MALDI: m/e 1131.31 (M+ + H), 1051.62 (M+ + H - SO3).
Anal. Calcd for C58H66O16SSe: C, 61.64; H, 5.89. Found: C, 61.30;
H, 5.97.
D
0.1, CH2Cl2). 1H NMR (CDCl3): δ 7.39-6.77 (13H, Ar-H), 5.32
(1H, s, Ph-CH-), 5.08 (1H, d, J3,2 ) 9.8 Hz, H-3), 4.50 (4H,
2×-MeO-Ph-CH2-), 4.46 (1H, dd, J1a,2 ) 4.8 Hz, H-1a), 4.32
(1H, dd, J1b,1a ) 10.1, J1b,2 ) 9.6 Hz, H-1b), 4.29 (1H, dd, J6a,5
)
5.6 Hz, H-6a), 4.21 (1H, ddd, H-2), 3.98 (1H, d, J4,5 ) 9.6 Hz,
H-4), 3.81, 3.72 (2×-OMe), 3.80 (1H, m, H-5), 3.60 (1H, dd, J6a,6b
) 10.4, J6b,5 ) 10.2 Hz, H-6b). 13C NMR (CDCl3): δ 160.0-
114.0 (18C, Ar), 101.5 (Ph-CH-), 82.2 (C-3), 76.3 (C-4), 73.3,
72.8 (2×-MeO-Ph-CH2-), 71.9 (C-1), 69.6 (C-6), 66.0 (C-5),
64.8 (C-2), 55.5, 55.4 (2×-OMe). MALDI: m/e 595.6 (M+ + Na).
Anal. Calcd for C29H32O10S: C, 60.83; H, 5.63. Found: C, 60.81;
H, 5.66.
2,3,5-Tri-O-p-methoxybenzyl-1,4-dideoxy-1,4-[[(2S,3S,4R,5R)-
4,6-O-benzylidene 2,5-Di-O-p-methoxybenzyl-3-(sulfooxy)hexyl]-
(R)-epi-sulfoniumylidene]-D-arabinitol Inner Salt (19). The thio-
arabinitol 14 (212 mg, 0.42 mmol) and the cyclic sulfate 13 (296
mg, 0.52 mmol) were added to 1,1,1,3,3,3-hexafluoroisopropanol
(HFIP) (3 mL) containing anhydrous K2CO3 (40 mg). The mixture
was stirred in a sealed tube at 65-70 °C for 42 h. The solvent was
removed under reduced pressure, and the residue was purified by
flash column chromatography (3:1 hexanes/EtOAc and then 20:1,
15:1 EtOAc/MeOH). The coupled product, 19, was obtained as a
white amorphous solid (350 mg, 77%). [R]23D ) -53.6° (c ) 0.1,
1
CH2Cl2). H NMR (d6-acetone): δ 5.37 (1H, s, Ph-CH-), 4.92
(1H, d, J3′,2′ ) 9.1 Hz, H-3′), 4.83-4.54 (10H, 5×-MeO-Ph-
CH2-), 4.50 (1H, m, H-3), 4.32 (3H, m, H-1a′, H-2′, H-6a′),
4.23 (1H, dd, J1b′,1a′ ) 13.6, J1b′,2′ ) 4.5 Hz, H-1b′), 4.16 (1H, m,
H-5′), 4.06 (1H, m, H-1a), 3.97-3.81 (3H, m, H-4, H-4′, H-1b),
3.80-3.66 (15H, 5×-OMe), 3.70 (2H, m, H2-5), 3.51 (1H, m,
H-6b′). 13C NMR (d6-acetone): δ 159.9-113.5 (36C, Ar), 100.6
(Ph-CH-), 83.6 (C-3), 81.9 (C-2), 77.9 (C-4′), 72.9 (C-2′), 72.4
(C-3′), 72.7, 72.6, 71.7, 71.4, 71.3 (5×-MeO-Ph-CH2-), 69.9
(C-6′), 67.2 (C-5′), 66.7 (C-5), 65.2 (C-4), 54.8, 55.7 (5×-OMe),
50.9 (C-1′), 48.0 (C-1). MALDI: m/e 1083.64 (M+ + H), 1003.29
(M+ + H - SO3). Anal. Calcd for C58H66O16S2: C, 64.31; H, 6.14.
Found: C, 64.61; H, 5.82.
1,4-Dideoxy-1,4-[[(2S,3S,4R,5R)-2,4,5,6-tetrahydroxy-3-(sul-
fooxy)hexyl]-(R/S)-epi-seleniumylidene]-D-arabinitol Inner Salts
(12 and 22). The selenonium salts 20 (240 mg, 0.212 mmol) and
21 (102 mg, 0.09 mmol) were deprotected separately using aq TFA
following the same procedure that was used for compound 11, to
give compounds 12 (80 mg, 85%) and 22 (32 mg, 81%),
respectively. Data for the trans isomer, 12: [R]23D ) +16.1° (c )
0.1, MeOH). 1H NMR (D2O): δ 4.82 (1H, dt, J2,1 ) 3.8, J2,3 ) 3.7
1,4-Dideoxy-1,4-[[(2S,3S,4R,5R)-2,4,5,6-tetrahydroxy-3-(sul-
fooxy)hexyl]-(R)-epi-sulfoniumylidene]-D-arabinitol Inner Salt
(11). To a solution of compound 19 (240 mg, 0.22 mmol) in CH2-
Cl2 (1 mL) were added trifluoroacetic acid (10 mL), followed by
H2O (4 mL). The mixture was stirred at room temperature for 2 h.
The solvents were then evaporated under diminished pressure, and
the residue was purified by flash column chromatography to give
Hz, H-2), 4.63 (1H, d, J3′,2′ ) 7.7 Hz, H-3′), 4.52 (1H, dd, J3,4 )
3.2 Hz, H-3), 4.44 (1H, ddd, J2′,1a′ ) 4.0, J2′,1b′ ) 7.2 Hz, H-2′),
4.19 (1H, ddd, J4,5a ) 5.1 Hz, J4,5b ) 8.9, H-4), 4.13 (1H, dd, J1a′,1b′
) 12.3 Hz H-1a′), 4.10 (1H, dd, J5a,5b ) 12.6 Hz, H-5a), 3.98 (1H,
dd, H-5b), 3.95 (1H, dd, H-1b′), 3.86 (3H, m, H-4′, H-5′, H-6a′),
3.82 (2H, d, H2-1), 3.69 (1H, dd, J6b′,6a′ ) 12.3, J6b′,5′ ) 5.7 Hz,
H-6b′). 13C NMR (D2O): δ 78.6 (C-3′), 77.6 (C-3), 77.6 (C-2),
70.1 (C-5′), 70.0 (C-4), 68.9 (C-4′), 66.1 (C-2′), 62.9 (C-6′), 59.4
(C-5), 49.1 (C-1′), 44.9 (C-1). MALDI: m/e 465.37 (M+ + Na),
363.29 (M+ + H - SO3). HRMS calcd for C11H22O11SSe (M -
11 as a white amorphous solid (72 mg, 82%). [R]23D ) -3.6° (c )
1
0.1, MeOH). H NMR (D2O): δ 4.77 (1H, ddd, J2,1 ) 4.0, J2,3
)
3.7 Hz, H-2), 4.67 (1H, d, J3′,2′ ) 8.1 Hz, H-3′), 4.48 (1H, dd, J3,4
) 3.2 Hz, H-3), 4.44 (1H, ddd, J2′,1a′ ) 3.3, J2′,1b′ ) 7.7 Hz, H-2′),
4.14 (1H, dd, J5a,4 ) 5.0 Hz, J5a,5b ) 10.8, H-5a), 4.10 (2H, m,
H-1a′, H-4), 3.98 (1H, dd, J5b′,4 ) 7.1 Hz, H-5b), 3.93 (1H, dd,
J1b′,1a′ ) 13.6 Hz, H-1a′), 3.91-3.87 (5H, m, H2-1, H-4′, H-5′,
H-6a′), 3.54 (1H, m, H-6b′). 13C NMR (D2O): δ 78.3 (C-3′), 77.8
H): 440.9964. Found: 440.9963. Data for the cis isomer, 22: [R]23
D
1
) +41.6° (c ) 0.1, MeOH). H NMR (D2O): δ 4.75 (1H, ddd,
J2,1b ) J2,1b ) 3.4, J2,3 ) 3.8 Hz, H-2), 4.64 (1H, d, J3′,2′ ) 8.0 Hz,
H-3′), 4.56 (1H, t, J3,4 ) 3.8 Hz, H-3), 4.41 (1H, ddd, J2′,1a′ ) 3.8,
J2′,1b′ ) 7.8 Hz, H-2′), 4.26 (1H, ddd, J4,5a) 5.5 Hz, J4,5b ) 9.0,
J. Org. Chem, Vol. 72, No. 1, 2007 185