1,4-dihydro-5H-pyran-O-4-methyl Carbonate (10). To a solution
of allylic alcohol 6 (400 mg, 0.50 mmol) in dry CH2Cl2 (1.0 mL)
at 0 °C was added pyridine (242 µL, 3.00 mmol), DMAP (30 mg),
and methyl chloroformate (283 mg, 3.00 mmol). After the solution
was stirred for 24 h at room temperature, water (3 mL) was added
and then the mixture was extracted with EtOAc (3 × 10 mL), dried
(Na2SO4), concentrated under reduced pressure. The crude product
was purified by using silica gel flash chromatography eluting with
EtOAc/hexane (15:85) to give carbonate 10 (402.4 mg, 0.45 mmol,
90%) as a viscous oil. Rf (30% EtOAc/hexane) )0.65; [R]26D +50
(c ) 1, CH2Cl2); IR (thin film, cm-1) 2928, 2885, 1748, 1441,
purified with silica gel flash chromatography eluting with MeOH/
EtOAc/hexane (10:40:50) to give allylic amine 4 (104 mg, 0.13
mmol, 80%) as a colorless oil. Rf 0.50 (10:40:50 MeOH/EtOAc/
hexane); [R]26D +24 (c 1, MeOH); IR (thin film, cm-1) 3361, 2944,
1
2833, 1740, 1448, 1374, 1240, 1120, 1040, 981, 847; H NMR
(600 MHz, CD3OD) δ 7.27 (m, 5H), 6.99 (m, 4H), 6.21 (d, J )
9.6 Hz, 1H), 5.91 (d, J ) 10.2 Hz, 1H), 5.84 (ddd, J ) 10.2, 10.2,
8.4 Hz, 1H), 5.69 (ddd, J ) 11.4, 10.2, 10.2 Hz, 1H), 5.59 (d, J )
2.4 Hz, 1H), 5.22 (br s, 1H), 5.02 (d, J ) 12.6 Hz, 1H), 4.95 (d,
J ) 12.6 Hz, 1H), 4.36 (m, 1H), 4.27 (d, J ) 9.0 Hz, 1H), 3.91
(dd, J ) 10.8, 4.2 Hz, 1H), 3.86 (m, 1H), 3.83 (dd, J ) 6.0, 3.0
Hz, 1H), 3.80 (dd, J ) 10.2, 4.2 Hz, 1H), 3.75 (dd, J ) 10.8, 6.0
Hz, 1H), 3.65 (s, 3H), 3.50 (ddd, J ) 9.6, 4.2, 3.6 Hz, 1H), 3.46
(ddd, J ) 9.0, 4.8, 4.2 Hz, 1H), 3.36 (dd, J ) 11.4, 9.6 Hz, 1H),
3.03 (ddd, J ) 8.4, 6.0, 5.4 Hz, 1H), 2.85 (ddd, J ) 8.4, 6.0, 5.4
Hz, 1H), 2.11 (s, 2H), 0.89 (d, J ) 4.2 Hz, 9H), 0.79 (d, J ) 5.4
Hz, 9H), 0.77 (d, J ) 4.2 Hz, 6H), -0.004 (s, 3H), -0.02 (d, J )
2.4 Hz, 3H); 13C NMR (150 MHz, CD3OD) δ 174.1, 158.5, 158.0,
138.3, 132.0, 131.7, 131.3, 129.5 (2C), 129.0, 128.7, 127.5, 118.5,
118.1, 94.5, 92.6, 74.8, 73.1, 68.3, 67.7, 65.0, 64.4, 57.2, 52.8, 37.9,
33.2, 30.8, 30.5, 30.0, 26.67 (3C), 26.61 (3C), 23.8, 19.4, 14.5,
-4.3, -4.6, -4.7, -4.9; CIHRMS calcd for [C42H64N2O10Si2H+]
813.4177, found 813.4177.
1
1509, 1266, 1090, 981, 865; H NMR (600 MHz, CDCl3) δ 7.34
(m, 5H), 7.00 (m, 4H), 6.18 (d, J ) 10.2 Hz, 1H), 6.01 (d, J )
10.2 Hz, 1H), 5.94 (dd, J ) 2.4, 1.8 Hz, 1H), 5.92 (ddd, J ) 10.8,
2.4, 1.8 Hz, 1H), 5.77 (ddd, J ) 10.2, 3.0, 1.8 Hz, 1H), 5.59 (d, J
) 1.8 Hz, 1H), 5.31 (dd, J ) 3.0, 1.8 Hz, 1H), 5.29 (dd, J ) 3.0,
2.4 Hz, 1H), 5.11 (d, J ) 12.6 Hz, 1H), 5.08 (d, J ) 12.6 Hz, 1H),
4.61 (ddd, J ) 8.4, 6.0, 5.4 Hz, 1H), 4.43 (d, J ) 9.6 Hz, 1H),
3.88 (dd, J ) 5.4, 2.4 Hz, 1H), 3.86 (dd, J ) 6.0, 2.4 Hz, 1H),
3.84 (dd, J ) 4.8, 1.8 Hz, 1H), 3.83 (dd, J ) 4.8, 2.4 Hz, 1H),
3.81 (dd, J ) 4.8, 1.8 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 1H), 3.71 (s,
3H), 3.07 (ddd, J ) 8.4, 5.4, 5.4 Hz, 1H), 3.05 (ddd, J ) 7.8, 6.0,
5.4 Hz, 1H), 0.89 (s, 9H), 0.84 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H),
0.02 (s, 3H), 0.01 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 171.9,
156.6, 155.6, 155.0, 136.2, 130.3, 130.1 (2C), 129.4, 129.0, 128.5
(2C), 128.1, 128.0, 127.6, 126.2, 117.2, 117.0, 109.9, 92.9, 91.0,
71.4, 69.3, 68.4, 66.9, 66.4, 62.7, 62.0, 54.9, 54.8, 52.2, 37.4, 25.93
(3C), 25.91 (3C), 18.43, 18.42, -5.0, -5.2, -5.4 (2C); CIHRMS
calcd for [C44H65NO13Si2Na+] 894.3892, found 894.3890.
(1′S,4′S,5′R,1S,4S,5R)-1-[1′-N-Carbobenzyloxy-D-tyrosine meth-
oxycarbonyl-5′-(tert-butyldimethylsilanyloxymethyl)-1′,4′-dihy-
dro-5′H-pyran-4′-yloxy]-5-(tert-butyldimethylsilanyloxymethyl)-
1,4-dihydro-5H-pyran-N-4-isovaleric Amide (11). The amine
compound 4 (100 mg, 0.12 mmol), isovaleric acid (15 mg, 0.15
mmol), and DCC (30 mg, 0.14 mmol) were dissolved in 0.3 mL of
CH2Cl2 in a round-bottomed flask and cooled to 0 °C then DMAP
(2 mg, 0.01 mmol) was added and the reaction mixture was stirred
at 0 °C for 6 h and on completion, as monitored by TLC, the
reaction mixture was diluted with ether and quenched with 5 mL
of satd aq NaHCO3, extracted (3 × 5 mL) with Et2O, dried (Na2-
SO4), and concentrated under reduced pressure. The crude product
was purified with silica gel flash chromatography eluting with
EtOAc/hexanes (30:70) to give amide 11 (94 mg, 0.10 mmol, 85%)
(1′S,4′S,5′R,1S,4S,5R)-1-[1′-N-Carbobenzyloxy-D-tyrosine meth-
oxycarbonyl-5′-(tert-butyldimethylsilanyloxymethyl)-1′,4′-dihy-
dro-5′H-pyran-4′-yloxy]-5-(tert-butyldimethylsilanyloxymethyl)-
4-azido-1,4-dihydro-5H-pyran (5). To a mixture of carbonate 10
(210 mg, 0.24 mmol), allylpalladium chloride dimer (13.2 mg, 0.03
mmol), and 1,4-bis(diphenylphosphino)butane (61.6 mg, 0.13
mmol) in anhydrous THF (0.25 mL) was added TMSN3 (277 mg,
1.20 mmol) under argon atmosphere. The solution was stirred at
room temperature for 3 h. Then the mixture was evaporated under
reduced pressure and purified with silica gel flash chromatography
eluting with EtOAc/hexane (15:85) to give allylic azide 5 (182 mg,
0.21 mmol, 88%) as a viscous oil. Rf (30% EtOAc/hexane) 0.70;
as a viscous oil. Rf (30% EtOAc/hexanes) 0.70; [R]26 +4 (c 1,
D
CH2Cl2); IR (thin film, cm-1) 2985, 2927, 1736, 1447, 1372, 1253,
1
1098, 1043, 938, 846; H NMR (600 MHz, CDCl3) δ 7.33 (m,
5H), 7.00 (m, 4H), 6.20 (d, J ) 10.8 Hz, 1H), 5.92 (ddd, J ) 10.2,
3.0, 1.8 Hz, 1H), 5.81 (d, J ) 10.2 Hz, 1H), 5.71 (ddd, J ) 10.2,
3.0, 2.4 Hz, 1H), 5.56 (d, J ) 2.4 Hz, 1H), 5.21 (m, 1H), 5.07 (br
s, 2H), 4.58 (dd, J ) 10.2, 5.4 Hz, 1H), 4.52 (d, J ) 8.4 Hz, 1H),
4.32 (d, J ) 9.0 Hz, 1H), 3.90 (m, 1H), 3.86 (d, J ) 11.4 Hz, 1H),
3.82 (m, 2H), 3.76 (ddd, J ) 11.4, 5.4, 4.8 Hz, 1H), 3.72 (dd, J )
11.4, 3.0 Hz, 1H), 3.69 (s, 3H), 3.66 (dd, J ) 3.0, 2.4 Hz, 1H),
3.64 (dd, J ) 4.2, 2.4 Hz, 1H), 3.03 (m, 2H), 2.11 (m, 1H), 2.00
(d, J ) 7.8 Hz, 2H), 0.93 (d, J ) 6.6 Hz, 6H), 0.87 (s, 9H), 0.80
[R]26 +65 (c 1, CH2Cl2); IR (thin film, cm-1) 2952, 2929, 2856,
D
1
2103, 1726, 1510, 1253, 1043, 993, 830; H NMR (600 MHz,
CDCl3) δ 7.35 (m, 5H), 6.99 (m, 4H), 6.18 (d, J ) 10.2 Hz, 1H),
6.00 (d, J ) 10.2 Hz, 1H), 5.94 (ddd, J ) 10.8, 2.4, 1.8 Hz, 1H),
5.83 (ddd, J ) 10.2, 3.0, 2.4 Hz, 1H), 5.59 (d, J ) 2.4 Hz, 1H),
5.26 (d, J ) 1.8 Hz, 1H), 5.11 (d, J ) 12.6 Hz, 1H), 5.08 (d, J )
12.6 Hz, 1H), 4.62 (ddd, J ) 7.8, 6.0, 5.4 Hz, 1H), 4.42 (d, J )
9.0 Hz, 1H), 4.14 (dd, J ) 3.8, 1.8 Hz, 1H), 4.12 (dd, J ) 10.2,
1.8 Hz, 1H), 3.92 (d, J ) 3.0 Hz, 1H), 3.90 (d, J ) 3.0 Hz, 1H),
3.88 (ddd, J ) 4.2, 3.6, 3.0 Hz, 1H), 3.86 (d, J ) 1.8 Hz, 1H),
3.80 (dd, J ) 4.2, 2.4 Hz, 1H), 3.71 (s, 3H), 3.65 (ddd, J ) 9.0,
3.0, 1.8 Hz, 1H), 3.08 (ddd, J ) 8.4, 6.0, 5.4 Hz, 1H), 3.04 (ddd,
J ) 8.4, 6.0, 5.4 Hz, 1H), 0.91 (s, 9H), 0.85 (s, 9H), 0.099 (s, 3H),
0.094 (s, 3H), 0.03 (s, 3H), 0.02 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 171.9, 156.6, 155.6, 136.2, 130.3, 130.1 (2C), 129.0 (2C),
128.5 (2C), 128.1, 128.0 (2C), 126.2, 117.2 (2C), 109.9, 92.9, 90.8,
71.3, 70.5, 66.9, 66.2, 62.6, 62.4, 54.8, 53.4, 52.2, 37.3, 25.9 (6C),
18.4 (2C), -5.0, -5.2 (2C), -5.3; CIHRMS calcd for [C42H62N4O10-
Si2Na+] 861.3902, found 861.3910.
(1′S,4′S,5′R,1S,4S,5R)-1-[1′-N-Carbobenzyloxy-D-tyrosine meth-
oxycarbonyl-5′-(tert-butyldimethylsilanyloxymethyl)-1′,4′-dihy-
dro-5′H-pyran-4′-yloxy]-5-(tert-butyldimethylsilanyloxymethyl)-
4-amino-1,4-dihydro-5H-pyran-(4). To a solution of azide 5 (140
mg, 0.16 mmol) in THF/H2O (9:1, v/v, 0.3 mL) was added (n-
Bu)3P (84 mg, 0.41 mmol), then the mixture was stirred at room
temperature for 1 h. The reaction mixture was evaporated with a
little silica gel under reduced pressure and the crude product was
(s, 9H), 0.04 (s, 3H), 0.03 (s, 3H), 0.00 (s, 3H), -0.02 (s, 3H); 13
C
NMR (150 MHz, CDCl3) δ 171.9, 156.6, 155.6, 136.2, 133.1, 130.5,
130.1, 129.0, 128.4 (2C), 128.1 (2C), 128.0 (2C), 126.1, 125.4 (2C),
117.2 (2C), 92.8, 91.1, 71.4, 70.0, 66.9 (2C), 66.8, 66.7, 65.3 (2C),
62.6, 54.8, 52.2, 37.3, 27.3, 25.9 (3C), 25.8 (3C), 24.0, 18.3, 18.2,
-5.0, -5.1, -5.4, -5.6; CIHRMS calcd for [C47H72N2O11Si2Na+]
919.4572, found 919.4543.
1′-N-carbobenzyloxy-D-tyrosine Methoxycarbonyl-5′,5-(tert-
butyldimethylsilanyloxymethyl)-di-1,4-R-D-mannose-N-4-isova-
leric Amide (12). To a CH2Cl2 (1.3 mL) solution of diene amide
11 (120 mg, 0.13 mmol) at 0 °C was added a solution of (50%
w/v) N-methyl morpholine N-oxide/water (0.1 mL). Crystalline
OsO4 (3.4 mg, 10 mol %) was added and the reaction was stirred
for 12 h. The reaction mixture was concentrated and pipetted
directly onto a silica gel column with CH2Cl2 (1 mL) in three
portions. Impurities were eluted with ether and the product was
eluted with MeOH/EtOAc/hexanes (10:40:50). Pure fractions were
combined and concentrated to afford bis-manno-amido-tetrol 12
(128 mg, 0.13 mmol, 80%) as a viscous oil. Rf (90% EtOAc/MeOH)
4968 J. Org. Chem., Vol. 72, No. 13, 2007