Synthesis of R- and â-Glycosyl Asparagine Ethylene Isosteres
J . Org. Chem., Vol. 67, No. 13, 2002 4485
3.0 Hz, H-1b), 3.88-3.82 (m, 1 H, H-2), 3.75 (dd, 1 H, H-8),
3.66-3.54 (m, 4 H), 1.99 (s, 3 H, Ac), 1.49 and 1.44 (2 s, 6 H,
2 Me), 1.44 (s, 9 H, t-Bu). MALDI-TOF MS: 752.2 (M+ + Na),
768.3 (M+ + K). Anal. Calcd for C42H52N2O9: C, 69.21; H, 7.19;
N, 3.84. Found: C, 69.20; H, 7.02; N, 3.95.
7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-2,3,4,5,7-
p e n t a d e oxy-2-(t er t -b u t oxyca r b on yla m in o)-D-t h r eo-L-
ga la cto-u n d econ ic Acid (75). Compound 69 (50 mg, 0.07
mmol) was treated with J ones reagent as described for the
preparation of 47 to give 75 (43 mg, 90%) as a syrup ∼90%
pure by 1H NMR analysis. 1H NMR selected data: δ 7.40-
7.20 (m, 15 H, 3 Ph), 5.31 (d, 1 H, J ) 7.0 Hz, NH), 4.90 and
4.58 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.72 and 4.40 (2 d, 2 H,
J ) 11.5 Hz, PhCH2), 4.70 (d, 1 H, J ) 8.0 Hz, NH), 4.52 and
4.40 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 1.94 (s, 3 H, Ac), 1.41 (s,
9 H, t-Bu).
Hz, PhCH2), 4.32 (ddd, 1 H, J 5a,6 ) 7.0 Hz, J 5b,6 ) 8.0 Hz, H-6),
3.76 (s, 3 H, OMe), 3.74-3.68 (m, 3 H), 3.64 (dd, 1 H, J 8,9
)
J 9,10 ) 9.0 Hz, H-9), 3.41-3.36 (m, 2 H), 2.19 (s, 3 H, Ac), 1.85-
1.55 (m, 6 H), 1.43 (s, 9 H, t-Bu). Anal. Calcd for C40H52N2O9:
C, 68.16; H, 7.44; N, 3.97. Found: C, 68.73; H, 7.44; N, 3.76.
7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-2,3,4,5,7-
pen tadeoxy-2-(ter t-bu toxycar bon ylam in o)-D-th r eo-L-gu lo-
u n d econ ic Acid (78). Compound 72 (34 mg, 0.04 mmol) was
treated with J ones reagent as described for the preparation
of 47 to give 78 (30 mg, 87%) as a syrup ∼95% pure by 1H
1
NMR analysis. H NMR selected data: δ 7.40-7.20 (m, 15 H,
3 Ph), 5.30 (d, 1 H, J ) 8.0 Hz, NH), 4.70 and 4.61 (2 d, 2 H,
J ) 11.7 Hz, PhCH2), 4.64 and 4.62 (2 d, 2 H, J ) 12.0 Hz,
PhCH2), 4.63 and 4.58 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 1.81 (s,
3 H, Ac), 1.43 (s, 9 H, t-Bu).
Meth yl 7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-
2,3,4,5,7-p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-
th r eo-L-gu lo-u n d econ a te (78a ). Treatment of a solution of
crude acid 78 in 1:1 Et2O-MeOH with ethereal diazomethane
at 0 °C for 5 min gave, after column chromatography on silica
gel (2:1 AcOEt-cyclohexane), 78a as a syrup. [R]D ) +23.3 (c
Meth yl 7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-
2,3,4,5,7-p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-
th r eo-L-ga la cto-u n d econ a te (75a ). Treatment of a solution
of crude acid 75 in 1:1 Et2O-MeOH with ethereal diaz-
omethane at 0 °C for 5 min gave, after column chromatography
1
on silica gel (2:1 cyclohexane-AcOEt), 75a as a syrup. [R]D
)
1.2, CHCl3). H NMR: δ 7.40-7.22 (m, 15 H, 3 Ph), 5.58 (d, 1
1
+27.0 (c 0.6, CHCl3). H NMR: δ 7.40-7.24 (m, 15 H, 3 Ph),
5.26 (d, 1 H, J 7,NH ) 7.0 Hz, NH), 5.02 (d, 1 H, J 2,NH ) 8.5 Hz,
NH), 4.92 and 4.63 (2 d, 2 H, J ) 11.6 Hz, PhCH2), 4.70 and
4.42 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.51 and 4.45 (2 d, 2 H,
J ) 11.8 Hz, PhCH2), 4.26 (ddd, 1 H, J 2,3a ) 5.5 Hz, J 2,3b ) 6.0
Hz, H-2), 4.03 (d, 1 H, J 8,9 ) 1.5 Hz, J 9,10 ) 0.5 Hz, H-9), 3.79
(ddd, 1 H, J 6,7 ) 9.3 Hz, J 7,8 ) 9.5 Hz, H-7), 3.70 (s, 3 H, OMe),
3.68-3.52 (m, 5 H), 1.92 (s, 3 H, Ac), 1.42 (s, 9 H, t-Bu). Anal.
Calcd for C40H52N2O9: C, 68.16; H, 7.44; N, 3.97. Found: C,
68.20; H, 7.50; N, 4.00.
H, J ) 8.0 Hz, NH), 5.04 (d, 1 H, J ) 8.0 Hz, NH), 4.74 and
4.63 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.59 and 4.54 (2 d, 2 H,
J ) 12.0 Hz, PhCH2), 4.56 and 4.47 (2 d, 2 H, J ) 12.0 Hz,
PhCH2), 3.71 (s, 3 H, OMe), 1.96 (s, 3 H, Ac), 1.44 (s, 9 H,
t-Bu). Anal. Calcd for C40H52N2O9: C, 68.16; H, 7.44; N, 3.97.
Found: C, 68.10; H, 7.48; N, 3.89.
7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-2,3,4,5,7-
p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-er yth r o-L-
gu lo-u n d econ ic Acid (79). Compound 73 (60 mg, 0.08 mmol)
was treated with J ones reagent as described for the prepara-
tion of 47 to give 79 (51 mg, 94%) as a syrup ∼95% pure by 1H
7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-2,3,4,5,7-
p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-er yth r o-L-
ga la cto-u n d econ ic Acid (76). Compound 70 (277 mg, 0.39
mmol) was treated with J ones reagent as described for the
preparation of 47 to give 76 (252 mg, 94%) as a syrup ∼95%
1
NMR analysis. H NMR selected data: δ 7.40-7.24 (m, 15 H,
3 Ph), 6.63 (d, 1 H, J ) 9.0 Hz, NH), 5.21-5.14 (m, 1 H, NH),
4.63-4.38 (m, 6 H), 4.35-4.17 (m, 3 H), 3.91-3.50 (m, 5 H),
1.92 (s, 3 H, Ac), 1.65-1.43 (m, 6 H), 1.41 (s, 9 H, t-Bu).
Meth yl 7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-
2,3,4,5,7-p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-
er yth r o-L-gu lo-u n d econ a te (79a ). Treatment of a solution
of crude acid 79 in 1:1 Et2O-MeOH with ethereal diazo-
methane at 0 °C for 5 min gave, after column chromatography
on silica gel (from 20:1 to 8:1 CH2Cl2-acetone), 79a as a white
solid. Mp: 103 °C (cyclohexane-AcOEt). [R]D ) +8.0 (c 0.5,
1
1
pure by H NMR analysis. H NMR selected data: δ 8.11 (d,
1 H, J 7,NH ) 7.5 Hz, NH), 7.40-7.18 (m, 15 H, 3 Ph), 4.87 and
4.65 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.82 and 4.56 (2 d, 2 H,
J ) 10.5 Hz, PhCH2), 4.62 (s, 2 H, PhCH2), 3.78-3.30 (m, 8
H), 1.83 (s, 3 H, Ac), 1.80-1.50 (m, 6 H), 1.45 (s, 9 H, t-Bu).
Meth yl 7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-
2,3,4,5,7-p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-
er yth r o-L-ga la cto-u n d econ a te (76a ). Treatment of a solu-
tion of crude acid 76 in 1:1 Et2O-MeOH with ethereal
diazomethane at 0 °C for 5 min gave, after column chroma-
tography on silica gel (2:1 cyclohexane-AcOEt), 76a as a
syrup. [R]D ) +32.2 (c 0.8, CHCl3). MALDI-TOF MS: 728.2
(M+ + Na), 744.3 (M+ + K). Anal. Calcd for C40H52N2O9: C,
68.16; H, 7.44; N, 3.97. Found: C, 68.00; H, 7.55; N, 4.03. The
1H NMR spectrum of 76a was identical to that of the product
prepared by another route.22
1
CHCl3). H NMR: δ 7.40-7.22 (m, 15 H, 3 Ph), 6.50 (d, 1 H,
J 2,NH ) 9.5 Hz, NH), 5.04 (d, 1 H, J 7,NH ) 8.0 Hz, NH), 4.62
and 4.51 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.60 and 4.45 (2 d, 2
H, J ) 11.5 Hz, PhCH2), 4.53 (s, 2 H, PhCH2), 4.30-4.24 (m,
1 H, H-2), 4.22-4.17 (m, 1 H), 4.16 (ddd, 1 H, J 6,7 ) 6.5 Hz,
J 7,8 ) 9.0 Hz, H-7), 3.88-3.74 (m, 3 H), 3.72 (s, 3 H, OMe),
3.69 (ddd, 1 H, J 5a,6 ) 1.0 Hz, J 5b,6 ) 3.5 Hz, H-6), 3.63-3.56
(m, 1 H), 1.85 (s, 3 H, Ac), 1.60-1.47 (m, 6 H), 1.45 (s, 9 H,
t-Bu). Anal. Calcd for C40H52N2O9: C, 68.16; H, 7.44; N, 3.97.
Found: C, 68.10; H, 7.48; N, 3.89.
7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-2,3,4,5,7-
p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-er yth r o-L-
glu co-u n d econ ic Acid (77). Compound 71 (64 mg, 0.09
mmol) was treated with J ones reagent as described for the
preparation of 47 to give 77 (57 mg, 92%) as a syrup ∼90%
pure by 1H NMR analysis. 1H NMR selected data: δ 7.41-
7.17 (m, 15 H, 3 Ph), 6.00 and 5.27 (2 bs, 2 NH), 4.85 and 4.42
(2 d, 2 H, J ) 11.0 Hz, PhCH2), 4.82 and 4.44 (2 d, 2 H, J )
11.0 Hz, PhCH2), 4.62 and 4.44 (2 d, 2 H, J ) 12.0 Hz, PhCH2),
3.76-3.62 (m, 5 H), 3.43-3.37 (m, 2 H), 2.10 (s, 3 H, Ac), 1.73-
1.65 (m, 6 H), 1.40 (s, 9 H, t-Bu).
Meth yl 7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-
2,3,4,5,7-p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-
er yth r o-L-glu co-u n d econ a te (77a ). Treatment of a solution
of crude acid 77 in 1:1 Et2O-MeOH with ethereal diaz-
omethane at 0 °C for 5 min gave, after column chromatography
7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-2,3,4,5,7-
p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-er yth r o-L-
a llo-u n d econ ic Acid (80). Compound 74 (50 mg, 0.07 mmol)
was treated with J ones reagent as described for the prepara-
tion of 47 to give 80 (36 mg, 75%) as a syrup ∼90% pure by 1H
1
NMR analysis. H NMR selected data: δ 7.40-7.24 (m, 15 H,
3 Ph), 6.01 (d, 1 H, J ) 9.0 Hz, NH), 5.16 (d, 1 H, J ) 7.0 Hz,
NH), 4.64-4.39 (m, 6 H), 3.87-3.64 (m, 6 H), 1.98 (s, 3 H,
Ac), 1.82-1.43 (m, 6 H), 1.45 (s, 9 H, t-Bu).
Meth yl 7-Aceta m id o-6,10-a n h yd r o-8,9,11-tr i-O-ben zyl-
2,3,4,5,7-p en t a d eoxy-2-(ter t-b u t oxyca r b on yla m in o)-D-
er yth r o-L-a llo-u n d econ a te (80a ). Treatment of a solution
of crude acid 80 in 1:1 Et2O-MeOH with ethereal diazo-
methane at 0 °C for 5 min gave, after column chromatography
on silica gel (from 8:1 to 6:1 CH2Cl2-acetone), 80a as a syrup.
1
on silica gel (1:1 cyclohexane-AcOEt), 77a as a syrup. [R]D
)
[R]D ) +21.1 (c 0.8, CHCl3). H NMR: δ 7.40-7.21 (m, 15 H,
-9.2 (c 1.0, CHCl3). 1H NMR: δ 7.41-7.18 (m, 15 H, 3 Ph),
5.71 (d, 1 H, J 7,NH ) 10.0 Hz, NH), 5.09 (d, 1 H, J 2,NH ) 9.0
Hz, NH), 4.91 and 4.46 (2 d, 2 H, J ) 10.8 Hz, PhCH2), 4.86
and 4.49 (2 d, 2 H, J ) 11.0 Hz, PhCH2), 4.67 (ddd, 1 H, J 6,7
) 4.0 Hz, J 7,8 ) 4.5 Hz, H-7), 4.64 and 4.50 (2 d, 2 H, J ) 12.0
3 Ph), 5.94 (d, 1 H, J ) 9.0 Hz, NH), 5.05 (d, 1 H, J ) 8.5 Hz,
NH), 4.78 and 4.50 (2 d, 2 H, J ) 11.0 Hz, PhCH2), 4.61 and
4.49 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.61 and 4.48 (2 d, 2 H,
J ) 11.5 Hz, PhCH2), 4.46-4.40 (m, 1 H), 4.28 (ddd, 1 H, J 5a,6
) 2.5 Hz, J 5b,6 ) 8.5 Hz, J 6,7 ) 2.5 Hz, H-6), 3.82-3.62 (m, 7