New Synthesis of Pyrrolidine Homoazasugars
d, 2 H, J ) 14.3 Hz, PhCH2N), 3.94 (dd, 1 H, J 8,9 ) 4.5, J 9,10
) 7.0 Hz, H-9), 3.87 (dd, 1 H, J 7,8 ) 7.0 Hz, H-8), 3.80 (dd, 1
H, J 10,11a ) 6.8, J 11a,11b ) 9.3 Hz, H-11a), 3.63 (dd, 1 H, H-7),
3.49 (dd, 1 H, J 10,11b ) 4.5 Hz, H-11b), 3.38 (ddd, 1 H, H-10),
3.15 (s, 3 H, OCH3), 1.47, 1.06 (2 s, 6 H, 2 CH3). Anal. Calcd
for C43H49NO7: C, 74.65; H, 7.14; N, 2.02. Found: C, 74.51;
H, 7.22; N, 2.12.
Hz, H-3), 4.53 and 4.45 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.44
(s, 2 H, PhCH2), 4.28 (dd, 1 H, H-2), 4.03-4.39 (m, 2 H, H-4,
H-10), 4.02 and 3.72 (2 d, 2 H, J ) 14.0 Hz, PhCH2N), 3.86
(dd, 1 H, J 8,9 ) 4.5 Hz, J 9,10 ) 2.0 Hz, H-9), 3.64-3.60 (m, 1
H, H-5), 3.59 (dd, 1 H, J 11,12a ) 4.5 Hz, J 12a,12b ) 10.0 Hz,
H-12a), 3.53 (dd, 1 H, J 11,12b ) 6,5 Hz, H-12b), 3.31-3.25 (m,
1 H, H-11), 3.15-3.07 (m, 1 H, H-8), 2.00-1.88 (m, 1 H, H-7a),
1.70-1.40 (m, 3 H, H-6a, H-6b, H-7b), 1.49, 1.40, 1.33, 1.30 (4
s, 12 H, 4 CH3). Anal. Calcd for C46H55NO8: C, 73.67; H, 7.39;
N, 1.87. Found: C, 73.89; H, 7.51; N, 1.98.
Aza -C-d isa cch a r id e 44. The olefin 43 (0.23 g, 0.33 mmol)
was reduced as described for the preparation of 41 to afford
after flash chromatography (5:1 cyclohexane-AcOEt with 0.3%
of triethylamine) 0.13 g (55%) of 44 as a syrup. [R]2D0 ) -6.4 (c
Aza -C-d isa cch a r id e 48. Compound 47 (0.15 g, 0.20 mmol)
was hydrogenated as described for the preparation of 42 to
1
0.9, CHCl3). H NMR: δ 7.40-7.20 (m, 20 H, 4 Ph), 4.85 (s, 1
1
afford 74 mg (95%) of a crude product (95% pure by H NMR
H, H-1), 4.60 (s, 2 H, PhCH2), 4.55-4.40 (m, 6 H, H-2, H-3, 2
PhCH2), 4.00 (dd, 1 H, J 8,9 ) 2.5 Hz, J 9,10 ) 5.5 Hz, H-9), 3.88
(s, 2 H, PhCH2), 3.80-3.72 (m, 3 H, H-4, H-8, H-11a), 3.48
(dd, 1 H, J 10,11b ) 4.5 Hz, J 11a,11b ) 9.2 Hz, H-11b), 3.34-3.25
(m, 1 H, H-10), 3.31 (s, 3 H, CH3), 2.84-2.77 (m, 1 H, H-7),
1.85-1.57 (m, 4 H, H-6a, H-6b, H7a, H-7b), 1.24, 1.30 (2 s, 6
H, 2 CH3). Anal. Calcd for C43H51NO7: C, 74.43; H, 7.41; N,
2.02. Found: C, 74.65; H, 7.30; N, 1.91.
analysis). 1H NMR (CD3OD): δ 5.01 (d, 1 H, J 1,2 ) 5.0 Hz,
H-1), 4.65 (dd, 1 H, J 2,3 ) 2.2 Hz, J 3,4 ) 8.0 Hz, H-3), 4.37 (dd,
1 H, H-2), 4.20 (dd, 1 H, J 4,5 ) 1.7 Hz, H-4), 3.98 (dd, 1 H, J 9,10
) J 10,11 ) 5.8 Hz, H-10), 3.91-3.76 (m, 4 H, H-5, H-9, H-12a,
H-12b), 3.46 (ddd, 1 H, J 11,12a ) 4.2 Hz, J 11,12b ) 6.2 Hz, H-11),
3.38-3.31 (m, 2 H, H-8, NH), 2.10-1.70 (m, 4 H, H-6a, H-6b,
H-7a, H-7b), 1.53, 1.44 (2 s, 6 H, 2 CH3), 1.36 (s, 6 H, 2 CH3).
The debenzylated product (74 mg, 0.19 mmol) was treated with
Amberlite IR-120 (H+) ion-exchange resin as decribed for the
preparation of 42 to obtain after gel permeation column
chromatography on Sephadex LH-20 (10:1 CH3OH-H2O) the
Aza -C-d isa cch a r id e 45. Compound 44 (0.14 g, 0.20 mmol)
was hydrogenated as described for the preparation of 42 to
1
afford 67 mg (100%) of a crude product (95% pure by H NMR
1
analysis). H NMR (CD3OD): δ 4.82 (s, 1 H, H-1), 4.69 (dd, 1
pure compound 48 (52 mg, 79%) as a colorless syrup. [R]D20
)
H, J 2,3 ) 6.0 Hz, J 3,4 ) 3.5 Hz, H-3), 4.56 (d, 1 H, H-2), 4.04
(dd, 1 H, J 8,9 ) 2.0 Hz, J 9,10 ) 4.2 Hz, H-9), 3.96 (ddd, 1 H,
J 4,5a ) J 4,5b ) 6.0 Hz, H-4), 3.86 (dd, 1 H, J 10,11a ) 5.8 Hz, J 11a,11b
) 11.5 Hz, H-11a), 3.80 (dd, 1 H, J 10,11b ) 6.5 Hz, H-11b), 3.77
(dd, 1 H, J 7,8 ) 4.0 Hz, H-8), 3.40-3.32 (m, 1 H, H-10), 3.32
(s, 3 H, OCH3), 3.04-2.96 (m, 1 H, H-7), 2.00-1.70 (m, 4 H,
H-5a, H-5b, H-6a, H-6b), 1.88, 1.62 (2 s, 6 H, 2 CH3). The
debenzylated product (67 mg, 0.20 mmol) was treated with
Amberlite IR-120 (H+) ion-exchange resin as described for the
preparation of 42 to obtain after gel permeation column
chromatography on Sephadex LH-20 (10:1 CH3OH-H2O) the
1
+42.5 (c 1.5, H2O). H NMR (D2O) (selected data): δ 5.10 (d,
0.3 H, J 1R,2R ) 3.8 Hz, H-1R), 4.42 (d, 0.7 H, J 1â,2â ) 8.0 Hz,
H-1â), 3.63 (dd, 0.3 H, J 2R,3R ) 10.0 Hz, H-2R), 3.32 (dd, 0.7 H,
J 2â,3â ) 10.0 Hz, H-2â), 1.95-1.50 (m, 4 H, 2 H-6R, 2 H-6â, 2
H-7R, 2 H-7â). MALDI-TOF MS (345.77): 311.9 (M + H - Cl).
Anal. Calcd for C12ClH24NO8: C, 41.68; H, 7.00; N, 4.05.
Found: C, 41.48; H, 6.91; N, 4.00.
Alk en e 49. The Wittig reaction was carried out as described
above for aza-C-disaccharide 43 starting from the aldehyde
20 (0.26 g, 0.50 mmol) and the phosphonium salt 39 (0.35 g,
0.60 mmol) to afford after flash chromatography (7:1 cyclo-
hexane-AcOEt with 0.3% of triethylamine) the syrup 49 (0.19
g, 54%) as (Z)-olefin contaminated by a small amount of the
(E)-isomer (by 1H NMR analysis). (Z)-49. 1H NMR (selected
data): δ 5.88 (dd, 1 H, J 5,6 ) 11.0 Hz, J 6,7 ) 8.0 Hz, H-6), 5.81
(dd, 1 H, J 4,5 ) 9.0 Hz, H-5), 4.14 (dd, 1 H, J 8,9 ) J 9,10 ) 3.2
Hz, H-9), 4.02 (dd, 1 H, J 7,8 ) 6.0 Hz, H-7), 3.98 and 3.65 (2 d,
2 H, J ) 14.0 Hz, PhCH2N), 3.92 (dd, 1 H, H-8), 3.61 (dd, 1 H,
J 10,11a ) 5.8 Hz, J 11a,11b ) 9.5 Hz, H-11a), 3.51 (dd, 1 H, J 10,11b
) 3.5 Hz, H-11b), 3.34-3.25 (m, 1 H, H-10), 3.28 (s, 3 H,
OCH3), 1.44, 1.24 (2 s, 6 H, 2 CH3).
pure compound 45 (53 mg, 95%) as a colorless syrup. [R]D20
)
+5.5 (c 0.3, H2O). 1H NMR (D2O) (selected data): δ 4.20-3.90
(m, 3 H), 3.86-3.58 (m, 3 H), 3.56-3.30 (m, 1 H), 3.10-2.90
(m, 1 H), 1.95-1.35 (m, 4 H, 2 H-5, 2 H-6). MALDI-TOF MS
(315.75): 281.6 (M + H - Cl). Anal. Calcd for C11ClH22NO7:
C, 41.84; H, 7.02; N, 4.44. Found: C, 41.60; H, 6.94; N, 4.32.
Alk en e 46. The Wittig reaction was carried out as described
above for the aza-C-disaccharide 40 starting from the aldehyde
20 (0.26 g, 0.50 mmol) and the phosphonium salt 38 (0.38 g,
0.60 mmol) to afford after flash chromatography (10:1 cyclo-
hexane-AcOEt with 0.3% of triethylamine) the syrup 46 (0.17
g, 46%) as a mixture of (Z)- and (E)-olefins in a 1:1 ratio (by
Aza -C-d isa cch a r id e 50. The olefin 49 (0.19 g, 0.27 mmol)
was reduced as described for the preparation of 41 to afford
after flash chromatogrphy (5:1 cyclohexane-AcOEt with 0.3%
of triethylamine) the compound 50 (0.11 g, 60%) as a syrup.
1
1H NMR analysis). (Z)-46. H NMR (selected data): δ 5.92-
5.79 (m, 2 H, H-6, H-7), 5.52 (d, 1 H, J 1,2 ) 5.0 Hz, H-1), 4.43
(dd, 1 H, J 2,3 ) 2.3 Hz, J 3,4 ) 8.0 Hz, H-3), 4.38-4.30 (m, 1 H,
H-5), 4.24 (dd, 1 H, H-2), 4.14-4.08 (m, 1 H, H-8), 4.08 and
[R]2D0 ) -39.1 (c 1.4, CHCl3). H NMR: δ 7.45-7.22 (m, 20 H,
1
3.66 (2 d, 2 H, J ) 14.0 Hz, PhCH2N), 3.99 (dd, 1 H, J 9,10
)
4 Ph), 4.86 (s, 1 H, H-1), 4.57 and 4.48 (2 d, 2 H, J ) 11.8 Hz,
PhCH2), 4.56 and 4.51 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.56-
4.52 (m, 2 H, H-2, H-3), 4.58 (s, 2 H, PhCH2), 4.03 and 3.73 (2
d, 2 H, J ) 14.0 Hz, PhCH2N), 4.03 (dd, 1 H, J 8,9 ) J 9,10 ) 2.5
Hz, H-9), 3.90 (dd, 1 H, J 7,8 ) 4.5 Hz, H-8), 3.88-3.80 (m, 1 H,
H-4), 3.62 (dd, 1 H, J 10,11a ) 5.0 Hz, J 11a,11b ) 9.5 Hz, H-11a),
3.56 (dd, 1 H, J 10,11b ) 6.5 Hz, H-11b), 3.32-3.28 (m, 1 H,
H-10), 3.30 (s, 3 H, OCH3), 3.18-3.12 (m, 1 H, H-7), 1.92-
1.63 (m, 4 H, H-5a, H-5b, H-6a, H-6b), 1.42, 1.46 (2 s, 6 H, 2
CH3). Anal. Calcd for C43H51NO7: C, 74.43; H, 7.41; N, 2.02.
Found: C, 74.59; H, 7.53; N, 2.13.
2.7 Hz, J 10,11 ) 4.3 Hz, H-10), 3.87 (dd, 1 H, J 8,9 ) 2.7 Hz,
H-9), 3.66-3.56 (m, 3 H, H-4, H-12a, H-12b), 3.32-3.24 (m, 1
H, H-11). (E)-46. 1H NMR (selected data): δ 5.85 (dd, 1 H,
J 6,7 ) 15.0 Hz, J 7,8 ) 6.5 Hz, H-7), 5.77 (dd, 1 H, J 5,6 ) 5.5 Hz,
H-6), 5.60 (d, 1 H, J 1,2 ) 5.0 Hz, H-1), 4.63 (dd, 1 H, J 2,3 ) 2.5,
J 3,4 ) 8.0 Hz, H-3), 4.63 and 4.52 (2 d, 2 H, J ) 11.5 Hz,
PhCH2), 4.54 and 4.50 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.48
and 4.43 (2 d, 2 H, J ) 12.5 Hz, PhCH2), 4.33 (dd, 1 H,
H-2),4.33-4.29 (m, 1 H, H-5), 4.20 (dd, 1 H, J 4,5 ) 2.0 Hz, H-4),
4.06 (dd, 1 H, J 9,10 ) J 10,11 ) 3.2 Hz, H-10), 3.99 and 3.65 (2 d,
2 H, J ) 14.5 Hz, PhCH2N), 3.89 (dd, 1 H, J 8,9 ) 5.0 Hz, H-9),
3.66 (dd, 1 H, H-8), 3.56-3.48 (m, 2 H, H-12a, H-12b), 3.31-
3.23 (m, 1 H, H-11).
Aza -C-d isa cch a r id e 51. Compound 50 (0.14 g, 0.20 mmol)
was hydrogenated as described for the preparation of 42 to
1
afford 69 mg (100%) of a crude product (95% pure by H NMR
1
Aza -C-d isa cch a r id e 47. Olefins 46 (0.17 g, 0.23 mmol)
were reduced as described for the preparation of 41 to afford
after flash chromatography (8:1 cyclohexane-AcOEt with 0.3%
triethylamine) the compound 47 (0.13 g, 77%) as a syrup. [R
analysis). H NMR (CD3OD): δ 4.82 (s, 1 H, H-1), 4.68 (dd, 1
H, J 2,3 ) 6.0 Hz, J 3,4 ) 3.5 Hz, H-3), 4.55 (d, 1 H, H-2), 3.98-
3.91 (m, 1 H, H-4), 3.79 (dd, 1 H, J 8,9 ) J 9,10 ) 6.5 Hz, H-9),
3.70 (dd, 1 H, J 10,11a ) 4.2 Hz, J 11a,11b ) 11.5 Hz, H-11a), 3.65
(dd, 1 H, J 7,8 ) J 8,9 ) 6.5 Hz, H-8), 3.62 (dd, 1 H, J 10,11b ) 6.0
Hz, H-11b), 3.35-3.30 (m, 1 H, NH), 3.32 (s, 3 H, OCH3), 3.03
(ddd, 1 H, H-10), 3.01-2.93 (m, 1 H, H-7), 1.97-1.71 (m, 3 H,
20
D
1
]
) -47.9 (c 0.6, CHCl3). H NMR: δ 7.40-7.20 (m, 20 H, 4
Ph), 5.53 (d, 1 H, J 1,2 ) 5.0 Hz, H-1), 4.55 and 4.47 (2 d, 2 H,
J ) 12.0 Hz, PhCH2), 4.54 (dd, 1 H, J 2,3 ) 2.3 Hz, J 3,4 ) 8.0
J . Org. Chem, Vol. 67, No. 21, 2002 7213