8190 J. Am. Chem. Soc., Vol. 118, No. 35, 1996
Martichonok and Whitesides
were prepared according to a modified published procedure.9 Reaction
of TMSE-protected lactose 6 with acetone dimethyl acetal and
subsequent benzylation afforded a mixture of acetonides 7 and 8, not
just 7 as reported.9 This mixture was separated by column chroma-
tography on silica gel eluting with 10% EtOAc in toluene. Treatment
of 7 with 80% aqueous acetic acid gave known7c acceptor 9 in 70%
overall yield. The same reaction of acetonide 8 afforded acceptor 10
in 11% overall yield. Compound 10 was crystallized from Et2O/
2-(Trimethylsilyl)ethyl 2,3,6-tri-O-benzyl-4-O-{2,3-di-O-benzyl-
6-O-[methyl [5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-3-[(2,4-
dimethyphenyl)thio]-D-erythro-r-L-gluco-2-nonulopyranosid]onate]-
â-D-galactopyranosyl}-â-D-glucopyranoside (14) was prepared in 83%
yield from 4 and 10 using the procedure for preparation of 11: Rf )
1
0.45 (20% acetone in CHCl3); [R]23 ) +17.2° (c 1.02, CHCl3); H
D
NMR (500 MHz, C6D6) δ 0.00 (s, 9 H, CH2Si(CH3)3), 1.00-1.10 (m,
2 H, CH2Si(CH3)3), 1.60 (s, 3 H), 1.66 (s, 3 H), 1.85 (s, 3 H), 1.86 (s,
3 H), 1.98 (s, 3 H), 2.21 (s, 3 H, CH3 aromatic), 2.35 (s, 3 H, CH3
aromatic), 2.75 (dd, J ) 4.03, 8.30, 1 H), 2.98 (d, J ) 3.06, 1 H, 4′-
OH), 2.36 (dd, J ) 3.99, 9.58 Hz, 1 H, H-5′), 3.31 (dd, J ) 3.11, 9.44
Hz, 1 H, H-3′), 3.36 (m, 1 H, H-5), 3.38 (d, J ) 10.86 Hz, 1 H, H-3′′),
3.52 (s, 3 H, CO2CH3), 3.61-3.66 (m, 2 H, H-2, OCH2CH2Si(CH3)3),
3.70 (t, J ) 8.85 Hz, 1 H, H-3), 3.73 (t, J ) 9.46 Hz, 1 H, H-4), 3.91
(dd, J ) 8.03, 9.25 Hz, 1 H, H-2′), 3.99 (dd, J ) 4.06, 9.88 Hz, 1 H,
H-6a), 4.04 (t, J ) 9.33, Hz, 1 H, H-6b), 4.12 (m, 1 H, OCH2CH2Si-
(CH3)3), 4.18 (dd, J ) 7.02, 12.50 Hz, 1 H, H-9a′′), 4.20 (dd, J )
9.47, 11.20 Hz, 1 H, H-6b′), 4.30 (t, J ) 2.73 Hz, 1 H, H-4′), 4.42 (d,
J ) 12.21 Hz, 1 H), 4.44 (d, J ) 7.59 Hz, 1 H, H-1), 4.48 (d, J )
12.12 Hz, 1 H), 4.50 (dd, J ) 2.24, 10.67 Hz, 1 H, H-6′′), 4.51 (d, J
) 7.77 Hz, 1 H, H-1′), 4.56 (d, J ) 11.64 Hz, 1 H), 4.62 (dd, J )
2.73, 12.36 Hz, 1 H, H-9b′′), 4.69 (q, J ) 10.64 Hz, 1 H, H-5′′), 4.78-
4.84 (m, 3 H), 4.92 (d, J ) 10.49 Hz, 1 H), 5.04 (d, J ) 11.63 Hz, 1
H), 5.18 (d, J ) 11.62 Hz, 1 H), 5.24 (d, J ) 10.49 Hz, 1 H), 5.45 (dd,
J ) 2.21, 7.51 Hz, 1 H, H-7′′), 5.66 (dt, J ) 2.76, 7.24 Hz, 1 H, H-8′′),
5.77 (t, J ) 10.52 Hz, 1 H, H-4′′), 6.76 (s, 1 H), 6.79 (d, J ) 7.97 Hz,
1 H), 7.06-7.68 (m, 26 H, aromatic); 13C NMR (100 MHz, CDCl3) δ
-1.41, 18.46, 20.61, 20.66, 20.75, 20.81, 21.10, 23.12, 49.73, 52.51,
54.70, 60.33, 62.32, 64.35, 67.27, 68.29, 68.98, 71.13, 72.12, 72.25,
72.42, 73.10, 74.74, 74.78, 75.10, 75.20, 77.18, 79.32, 80.74, 81.74,
82.63, 101.29, 102.86, 103.10, 127.26, 127.38, 127.43, 127.47, 127.53,
127.57, 127.63, 127.77, 127.95, 128.00, 128.17, 128.22, 128.26, 128.29,
129.38, 130.96, 134.34, 138.36, 138.39, 138.42, 138.74, 139.30, 140.47,
167.83, 169.39, 170.00, 170.24, 170.62, 171.01; MS (FAB) calcd for
C80H99NO23SSiNa (M + Na) 1524, found 1524.
pentane: Rf ) 0.31 (33% EtOAc in hexanes); mp 112-114 °C; [R]23
D
) +23.8° (c 1.33, CHCl3); 1H NMR (500 MHz, C6D6) -0.14 (s, 9 H,
Si(CH3)3), 0.96-1.07 (m, 2 H, CH2TMS), 2.20-2.38 (br s, 1 H, OH-
6), 2.42 (d, J ) 9.16 Hz, 1 H, OH-4), 3.03 (m, 1 H, H-5′), 3.15 (dd,
J ) 3.27, 9.29 Hz, 1 H, H-3′), 3.41 (br dd, J ) 2.51, 9.84 Hz, 1 H,
H-5), 3.55-3.66 (m, 4 H, OCH2CH2TMS, H-2, H-6a′, H-6b′), 3.71 (t,
J ) 9.00 Hz, 1 H, H-3), 3.74-3.84 (m, 3 H, H-2′, H-6a, H-4′), 3.96
(dd, J ) 4.06, 10.94 Hz, 1 H, H-6b), 4.08-4.14 (m, 1 H, OCH2CH2-
TMS), 4.24 (dt, J ) 2.11, 9.38 Hz, 1 H, H-4), 4.36-4.41 (m, 3 H, 3
CH2Ph), 4.43 (d, J ) 7.71 Hz, 1 H, H-1), 4.52 (d, J ) 12.13 Hz, 1 H),
4.58 (d, J ) 7.83 Hz, 1 H, 1 H′), 4.78 (d, J ) 11.36 Hz, 1 H), 4.86 (d,
J ) 11.79 Hz, 1 H), 4.89 (d, J ) 11.46 Hz, 1 H), 4.94 (d, J ) 10.82
Hz, 1 H), 5.08 (d, J ) 11.51 Hz, 1 H), 5.26 (d, J ) 10.82 Hz, 1 H),
7.05-7.32 (m, 19 H, aromatic), 7.39 (d, J ) 7.40 Hz, 2 H, aromatic),
7.44 (d, J ) 7.60 Hz, 2 H, aromatic), 7.62 (d, J ) 7.62 Hz, 2 H,
aromatic); HRMS (FAB) calcd for C52H64O11SiNa (M + Na) 915.4116,
found 915.4110.
2-(Trimethylsilyl)ethyl 2,3,6-Tri-O-benzyl-4-O-{2,6-di-O-benzyl-
3-O-[methyl [5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-3-[(2,4-
dimethyphenyl)thio]-D-erythro-r-L-gluco-2-nonulopyranosid]onate]-
â-D-galactopyranosyl}-â-D-glucopyranoside (11). Toluene (2 × 20
mL) was evaporated from the mixture of 4 (591 mg, 0.9 mmol) and 9
(981 mg, 1.1 mmol). The mixture was dissolved in CH3CN (20 mL)
and DTBP (337 µL, 1.5 mmol) and dried, and crushed molecular sieves
4 Å (3.0 g) were added. The mixture was stirred at rt for 0.5 h, then
AgOTf (308 mg, 1.20 mmol) was added, and stirring was continued in
the dark for an additional 1 h. After cooling to -40 °C, PhSCl (116
µL, 0.19 mmol) was added dropwise and the mixture was stirred at
-40 °C for 1 h. Diisopropylamine (280 µL, 0.35 mmol) was added,
and the mixture was stirred at -40 °C for 0.5 h. A suspension of
silica gel (10 g) in EtOAc (75 mL) was added to the cold reaction
mixture. After filtration through a fritt and concentration in Vacuo,
the reaction mixture was chromatographed, eluting with 10% acetone
in CHCl3 f 15% acetone in CHCl3 to give trisaccharide 11 (1.05 g,
2-(Trimethylsilyl)ethyl 2,3,6-Tri-O-benzyl-4-O-{2,6-di-O-benzyl-
4-O-acetyl-3-O-[methyl [5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-
dideoxy-3-[(2,4-dimethyphenyl)thio]-D-erythro-r-L-gluco-2-nonu-
lopyranosid]onate]-â-D-galactopyranosyl}-â-D-glucopyranoside (12).
Compound 11 (1.43 g, 0.95 mmol) was acetylated in a mixture of CH2-
Cl2 (10 mL), pyridine (5 mL), Ac2O (2.5 mL), and a few crystals of
DMAP to give 12 (1.42 g, 97%): Rf ) 0.51 (33% CH3CN in toluene);
1
[R]23 ) +18.6° (c 1.61, CHCl3); a signal for H-4′ in H NMR (500
78%): Rf ) 0.48 (20% acetone in CHCl3); [R]23 ) +13.7°(c 0.99,
D
D
1
MHz, C6D6) was detected at δ 5.84 (d, J ) 3.26 Hz); MS (FAB) calcd
for C82H101NO24SSiNa (M + Na) 1566, found 1566.
CHCl3); H NMR (500 MHz, C6D6) δ -0.37 (s, 9 H, CH2Si(CH3)3),
0.99 (m, 2 H, CH2Si(CH3)3), 1.54 (s, 3 H), 1.69 (s, 3 H), 1.70 (s, 3 H),
1.83 (s, 3 H), 1.92 (s, 3 H), 2.01 (s, 3 H, CH3 aromatic), 2.20 (s, 3 H,
CH3 arom), 3.03 (br s, 1 H, 4-OH), 3.40 (m, 1 H, H-5), 3.47 (s, 3 H,
CO2CH3), 3.50 (d, J ) 11.37 Hz, 1 H, H-3′′), 3.58 (t, J ) 8.92 Hz, 1
H, H-2), 3.61 (m, 1 H, OCH2CH2Si(CH3)3), 3.69 (dd, J ) 5.55, 9.55
Hz, 1 H, H-6a′), 3.75 (t, J ) 9.10 Hz, 2 H, H-3), 3.77 (t, J ) 9.53 Hz,
1 H, H-2′), 3.88 (m, 1 H, H-5′), 3.89 (br s, 1 H, H-4′), 3.95 (dd, J )
4.33, 10.95 Hz, 1 H, H-6a), 3.99 (dd, J ) 7.20, 9.55 Hz, 1 H, H-6b′),
4.10 (dt, J ) 7.00, 9.50 Hz, 1 H, OCH2CH2Si(CH3)3), 4.16 (dd, J )
6.37, 12.52 Hz, 1 H, H-9a′′), 4.22 (dd, J ) 2.31, 10.85 Hz, 1 H, H-6′′),
4.22-4.34 (m, 4 H, H-6b, H-4, NH C NNH2Ph), 4.43 (d, J ) 7.55 Hz,
1 H, H-1), 4.44 (d, J ) 11.98 Hz, 1 H), 4.56 (d, J ) 11.89 Hz, 1 H),
4.63 (d, J ) 11.25 Hz, 1 H), 4.65 (m, 2 H, H-5′′, H-9′′), 4.69 (d, J )
12.55 Hz, 1 H), 4.73 (dd, J ) 3.24, 9.44 Hz, 1 H, H-3′), 4.86 (d, J )
11.57 Hz, 1 H), 4.90 (d, J ) 12.58 Hz, 1 H), 4.92 (d, J ) 7.89 Hz, 1
H, H-1′), 4.96 (d, J ) 10.95 Hz, 1 H), 5.07 (d, J ) 11.47 Hz, 1 H),
5.30 (d, J ) 10.94 Hz, 1 H), 5.42 (dd, J ) 2.30, 7.69 Hz, 1 H, H-7′′),
5.48 (t, J ) 10.77 Hz, 1 H, H-4′′), 5.69 (dt, J ) 2.50, 7.80 Hz, 1 H,
H-8′′), 6.70 (s, 1 H), 6.74 (d, J ) 7.99 Hz, 1 H), 7.05-7.68 (m, 26 H,
aromatic); 13C NMR (100 MHz, CDCl3) δ -1.43, 18.46, 20.51,
20.61, 20.64, 20.80, 20.93, 23.15, 49.89, 52.83, 57.37, 62.14, 67.09,
67.13, 67.25, 68.59, 68.71, 72.44, 72.51, 72.54, 72.96, 73.18, 74.10,
74.88, 76.36, 76.68, 77.00, 77.32, 78.40, 82.01, 82.78, 100.44, 102.49,
103.01, 126.83, 127.13, 127.18, 127.29, 127.33, 127.40, 127.42, 127.47,
128.17, 128.22, 128.35, 130.13, 131.11, 134.28, 138.21, 138.46, 138.72,
138.83, 139.15, 139.24, 140.18, 168.56, 169.31, 169.95, 170.21, 170.45,
170.95; MS (FAB) calcd for C80H99NO23SSiNa (M + Na) 1524,
found 1524.
2-(Trimethylsilyl)ethyl 2,3,6-Tri-O-benzyl-4-O-{2,3-di-O-benzyl-
4-O-acetyl-6-O-[methyl [5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-
dideoxy-3-[(2,4-dimethyphenyl)thio]-D-erythro-r-L-gluco-2-nonu-
lopyranosid]onate]-â-D-galactopyranosyl}-â-D-glucopyranoside (15).
Compound 15 was prepared in 96% yield as described for 12: Rf )
0.52 (33% CH3CN in toluene); [R]23 ) +19.8° (c 1.22, CHCl3); a
D
1
signal for H-4′ in H NMR (500 MHz, C6D6) was detected at δ 5.66
(d, J ) 3.59); MS (FAB) calcd for C82H101NO24SSiNa (M + Na) 1566,
found 1566.
2-(Trimethylsilyl)ethyl 2,3,6-Tri-O-benzyl-4-O-{4-O-acetyl-2,6-
di-O-benzyl-3-O-[methyl [5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-
dideoxy-D-erythro-r-L-gluco-2-nonulopyranosid]onate]-â-D-galac-
topyranosyl}-â-D-glucopyranoside (13). AIBN (170 mg, 1.04 mmol)
was added in small portions every 1 h over a period of 10 h to the
mixture of 12 (1.26 g, 0.82 mmol) and Ph3SnH (2.88 g, 0.82 mmol) in
refluxing toluene (60 mL) under N2. The reaction was then refluxed
for an additional 5 h, cooled, and applied directly to a silica gel column.
Elution (20% acetonitrile in toluene f 33% acetonitrile in toluene,
gradient) gave the unreacted starting material 12 (49 mg, 4%) and the
product 13 (1.08 g, 94%): Rf
) 0.38 (33% CH3CN in toluene), [R]23
D
) -7.2° (c 0.85, CHCl3); 1H NMR (500 MHz, C6D6) δ -0.29 (s, 9H,
Si(SH3)3), 0.98 (m, 2H, CH2Si(SH3)3), 1.59 (s, 3H), 1.60 (s, 3H), 1.74
(s, 3H), 1.76 (s, 3H), 1.81 (s, 3H), 2.00 (t, J ) 12.70 Hz, 1 H, H-3ax′′),
2.09 (s, 3H), 2.84 (dd, J ) 4.68, 12.71 Hz, 1 H, H-3eq′′), 3.38-3.47
(m, 3 H, H-5, H-5′, H-6a′), 3.57-3.63 (m, 3 H, H-2, H-6′′, OCH2CH2-
TMS), 3.74 (t, J ) 9.04, 1 H, H-3), 3.79 (s, 3 H, CO2CH3), 3.83 (dd,
J ) 7.88, 9.46 Hz, 1 H, H-2′), 3.92 (d, J ) 10.45, 1 H), 3.96 (dd, J )