K.-k. T. Mong et al.
separated, dried (over MgSO4), filtered, and concentrated for chromatog-
raphy purification (elution: EtOAc/hexane/CH2Cl2 1:2:1 to 3:1:1) to fur-
nish the glucosylamine 3a as a yellow foam (55 mg, 36%). Rf =0.33
(EtOAc/CH2Cl2 1:8); 1H NMR (300 MHz, CDCl3): d=7.35–7.26 (m,
13H; Ar), 7.14–7.11 (m, 2H; Ar), 4.85–4.47 (m, 7H), 4.08 (d, J=9 Hz,
1H; H-1), 3.73–3.63 (m, 4H), 3.54–3.50 (m, 1H; H-5), 1.99 (s, 3H; CH3),
1.94 ppm (br, NH2); 13C NMR (CDCl3, 75 MHz): d=170.9, 138.7, 138.3,
138.26, 129.1, 128.9, 128.43, 128.37, 128.28, 128.18, 128.14, 128.10, 127.97,
pieces of Na2S2O3 (s), and satd. NaHCO3 (2 mL). The mixture was stirred
for 1–2 h at RT until the color of solution had changed to pale yellow,
and the mixture was dried (over MgSO4), filtered, and concentrated for
flash chromatography over silica gel (elution: EtOAc/hexane 1: 8) to give
the disaccharide 29 as a colorless oily substance (1.85 g, a/b 10:1, 85%).
a-Anomer: Rf =0.4 (elution: hexane/Et2O/CH2Cl2 8:1:0.4); [a]2D7 = +58.1
(c=0.36 in CHCl3); H NMR (CDCl3, 300 MHz): d=8.10 (d, J=7.5 Hz,
2H; Ar), 8.01 (d, J=7.2 Hz, 2H; Ar), 7.68–7.44 (m, 10H; Ar), 7.41–7.08
(m, 20H; Ar), 5.71 (d, J=0.6 Hz, 1H; H-1), 5.66–5.63 (m, 2H), 5.16 (s,
1H; H-1’), 4.71 (q, J=4.2 Hz, 1H), 4.49–4.40 (m, 4H), 4.26–4.19 (m,
1H), 4.15 (dd, J=4.5, 11.0 Hz, 1H), 4.07–4.04 (m, 2H), 3.85 (dd, J=4.2,
11.1 Hz, 1H), 3.78 (d, J=4.5 Hz, 2H), 2.29 (s, 3H; CH3), 1.02 ppm (s,
9H; tBu); 13C NMR (CDCl3, 75 MHz): d=165.4 (C=O), 165.3 (C=O),
137.91, 137.85, 137.6, 135.7, 135.6, 133.4, 132.6, 130.00, 129.9, 19.3, 129.8,
129.6, 129.2, 129.1, 128.5, 128.4, 128.3, 128.2, 127.7, 127.64, 127.61, 127.57,
127.5, 106.2 (C-1’), 91.6 (C-1), 88.4, 82.8, 82.5, 82.3, 81.7, 77.9, 71.8, 66.0,
85.3
(CH3)3).
Synthesis of (3aS,5R,6R,7S,7aR)-6,7-bis(benzyloxy)-5-[benzyloxymethyl]-
2-methyl-5H-pyrano[2,3-d]oxazoline (3e) from the fully protected thio-
ACHTUNGTRENNUNG(C-1), 84.1, 78.6, 76.2, 75.6, 75.4, 74.8, 73.9, 65.3 (C-6), 21.5 ppm (C-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
glucoside 3:[28] Tf2O (77 mL, 0.46 mmol) was added at ꢁ258C under N2 to
a cooled solution of the thioglucoside 3 (300 mg, 0.46 mmol) in CH3CN
(16 mL). After the mixture had been stirred for 1 h, NIS (110 mg,
0.49 mmol) was added. Upon completion of activation of 3, triethylamine
(0.5 mL) was added. The crude mixture was then treated with sat.
NaHCO3 (0.3 mL) and Na2S2O3 (s, ca. 1.5 g) and stirred vigorously at RT.
After the crimson color of the mixture had turned to pale yellow, the
mixture was then separated, dried (over MgSO4), filtered, and concen-
trated for standard chromatography purification (elution: EtOAc/hexane/
CH2Cl2 1:3:1 to 2:1:1, the silica gel was pre-neutralized as described
before) to furnish the glucosyl oxazoline 18a as a colorless syrup (79 mg,
37%).
63.6, 26.8 (CACHTNUTRGENN(UG CH3)3), 21.1 ppm (CACHTUGNTRENN(UNG CH3)3); HRMS: m/z calcd for
C61H62NaO10SSi [M+Na]+: 1037.3725; found: 1037.3731 (100).
Synthesis of 2,3-di-O-benzyl-5-O-(tert-butyldiphenylsilyl)-a-d-arabinofur-
anosyl-(1!5)-1,2;3,4-di-O-isopropylidene-a-d-galactopyranose (30): The
disaccharide 30 was prepared from the thioarabinofuranoside 22 (168 mg,
0.25 mmol) and the galactosyl acceptor 7 (50 mg, 0.19 mmol) by the LCG
procedure as described for the synthesis of 29. The crude reaction mix-
ture (after workup) was concentrated for flash chromatography over
silica gel (elution: EtOAc/hexane 1:10) to give 30 as a colorless oily sub-
stance (130 mg, a/b 10:1, 83%). a-Anomer: Rf =0.3 (EtOAc/hexane 1:6);
[a]2D7 =ꢁ31.2 (c=0.62 in CHCl3); 1H NMR (CDCl3, 300 MHz): d=7.67–
7.63 (t, J=6 Hz, 4H; Ar), 7.40–7.2 (m, 16H; Ar), 5.53 (d, J=4.8 Hz, 1H;
H-1), 5.16 (s, 1H; H-1’), 4.63–4.56 (m, 2H), 4.54–4.46 (m, 3H), 4.31–4.27
(m, 2H), 4.16–4.15 (m, 1H), 4.08–4.03 (m, 3H), 3.85–3.71 (m, 4H), 1.45
(d, J=6.3 Hz, 6H; CH3 ꢂ2), 1.30 (d, J=2.4 Hz, 6H; CH3 ꢂ2), 1.03 ppm
(s, 9H; tBu); 13C NMR (CDCl3, 75 MHz): d=138.0, 137.7, 135.62, 135.57,
Synthesis of p-tolyl 2,3-di-O-benzyl-5-O-(tert-butyldiphenylsilyl)thio-a-d-
arabinofuranoside (22):[42] The preparation procedure is given in the Sup-
porting Information. Rf =0.3 (EtOAc/hexane 1:15); 1H NMR (CDCl3,
300 MHz): d=7.68–7.64 (m, 4H; Ar), 7.42–7.25 (m, 18H; Ar), 7.10–7.07
(m, 2H; Ar), 5.51 (d, J=2.4 Hz, 1H; H-1), 4.60 (d, J=11 Hz, 1H), 4.54–
4.49 (m, 3H), 4.31 (m, 1H), 4.12 (d, J=3 Hz, 2H), 3.89–3.78 (m, 2H),
2.32 (s, 3H; CH3), 1.04 ppm (s, 9H; tBu); 13C NMR (CDCl3, 75 MHz):
d=137.7, 137.4, 137.1, 135.61, 135.55, 133.2, 133.3, 131.8, 131.1, 129.6,
128.33, 128.29, 127.8, 127.7, 127.6, 127.5, 90.4 (C-1), 88.3, 83.1, 81.9, 72.1,
133.4, 133.3, 129.6, 128.30, 128.25, 127.7, 127.6, 127.5, 109.1 (C
108.5 (C(CH3)2), 106.3 (C-1’), 96.3 (C-1), 88.0, 83.1, 82.3, 72.0, 71.6, 70.8,
70.61, 70.56, 65.6, 65.4, 63.6, 52.3, 26.8 (C(CH3)3), 26.0, 24.9, 24.5,
19.3 ppm (C
(CH3)3); EI-MS: m/z calcd for C47H58NaO10Si [M+Na]+:
ACHTUNGTRENNUNG(CH3)2),
63.3, 72.0, 26.7 (CACHTUNGTRENNUNG(CH3)3), 21.1, 19.2 ppm (CCAHTUNGTREN(NUGN CH3)3).
AHCTUNGTRENNUNG
Synthesis of p-tolyl 2,3,5-tri-O-benzylthio-a-d-arabinofuranoside (23):[53]
The procedure is given in the Supporting Information. Rf =0.3 (EtOAc/
hexane 1:15); 1H NMR (CDCl3, 300 MHz): d=7.42–7.39 (m, 2H; Ar),
7.32–7.27 (m, 15H; Ar), 7.11–7.08 (m, 2H; Ar), 5.55–5.54 (m, 1H), 4.65–
4.46 (m, 6H), 4.41–4.37 (m, 1H), 4.12–4.10 (m, 1H), 4.05–4.02 (m, 1H),
3.72–3.60 (m, 2H), 2.31 ppm (s, 3H; CH3); 13C NMR (CDCl3, 75 MHz):
d=137.9, 137.5, 137.2, 131.8, 130.8, 129.5, 128.3, 128.22, 128.16, 127.82,
127.77, 127.7, 127.6, 127.4, 90.4, 88.2, 83.2, 80.2, 77.4, 77.00, 76.6, 73.1,
72.1, 71.9, 68.8, 21.0 ppm.
Synthesis of p-tolyl 2,3-di-O-benzoylthio-a-d-arabinofuranoside (25):[54]
The preparation procedure is given in the Supporting Information. Rf =
0.3 (EtOAc/hexane 3:7); 1H NMR (CDCl3, 300 MHz): d=8.12 (dd, J=
0.6, 7.8 Hz, 2H; Ar), 8.03 (dd, J=0.6, 7.8 Hz, 2H; Ar), 7.63–7.41 (m, 8H;
Ar), 7.13 (d, J=8.4 Hz, 2H; Ar), 5.72 (d, J=1.2 Hz, 2H), 5.54 (d, J=
3.9 Hz, 1H), 4.58 (dd, J=3.9, 4.5 Hz, 1H), 4.03 (d, J=2.1 Hz, 1H), 2.41
(brs, 1H; OH), 2.32 ppm (s, 3H; CH3); 13C NMR (CDCl3, 75 MHz): d=
165.7, 165.0, 137.9, 133.4, 132.6, 129.8, 129.7, 128.8, 128.7, 128.3, 91.5 (C-
1), 83.6, 81.9, 76.6, 61.7, 20.9 ppm.
Synthesis of methyl 2,3-di-O-benzylthio-a-d-arabinofuranoside (27):[55]
The preparation procedure is given in the Supporting Information. Rf =
0.4 (EtOAc/hexane 1:10); 1H NMR (CDCl3, 300 MHz): d=7.33–7.25 (m,
10H; Ar), 4.92 (s, 1H; H-1), 4.58–4.51 (m, 2H), 4.86–4.29 (m, 2H), 4.14–
4.09 (m, 1H), 3.99–3.94 (m, 2H), 3.80–3.77 (m, 1H), 3.63–3.58 (m, 1H),
3.35 (s, 3H; OCH3), 2.49 ppm (br, 1H; OH); 13C NMR (CDCl3,
75 MHz): d=137.4, 137.0, 128.11, 28.08, 127.6, 127.5, 107.0 (C-1), 87.6,
82.4, 82.0, 71.9, 71.5, 61.7, 54.5 ppm.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
833.37; found: 833.63 (100).
Synthesis of methyl 2,3-di-O-benzyl-5-O-(tert-butyldiphenylsilyl)-a-d-ara-
binofuranosyl-(1!5)-2,3-di-O-benzyl-a-d-arabinofuranoside (31): The
disaccharide 31 was prepared from the thioarabinofuranoside 22 (255 mg,
0.38 mmol) and the thioarabinofuranosyl acceptor 27 (100 mg,
0.29 mmol) by the LCG procedure as described for the synthesis of 29.
The crude reaction mixture (after workup) was concentrated for flash
chromatography over silica gel (elution: EtOAc/hexane 1:10) to give 31
as a colorless oily substance (246 mg, a/b 12:1, 95%). a-Anomer: Rf =0.2
(EtOAc/hexane 1:10); [a]2D7 = +43.7 (c=0.53 in CHCl3); 1H NMR
(CDCl3, 300 MHz): d=7.69–7.65 (t, J=5.7 Hz, 4H; Ar), 7.41–7.19 (m,
26H; Ar), 5.16 (s, 1H; H-1’), 4.92 (s, 1H; H-1), 4.56–4.42 (m, 8H), 4.20–
4.15 (m, 2H), 4.08–4.03 (m, 3H), 4.00–3.99 (m, 1H), 3.88 (dd, J=4.5,
11.5 Hz, 1H), 3.81–3.80 (d, J=4.2 Hz, 2H), 3.69 (dd, J=3.6, 11.5 Hz,
1H), 3.37 (s, 3H; CH3), 1.04 ppm (s, 9H; tBu); 13C NMR (CDCl3,
75 MHz): d=138.0, 137.9, 137.7, 137.5, 135.63, 135.58, 133.41, 129.60,
128.3, 128.29, 128.23, 127.81, 127.74, 127.60, 127.56, 127.50, 107.1 (C-1),
106.3 (C-1’), 88.3, 88.0, 83.20, 82.4, 80.6, 72.2, 71.9, 71.8, 71.7, 66, 63.6,
54.8 (CH3), 26.7 (CACHTUNGTRNNEUG(CH3)3), 19.2 ppm (CAHCTUNGTRENN(UNG CH3)3); HRMS (EI): m/z calcd
for C55H62NaO9Si [M+Na]+: 917.4055; found: 917.4095.
Synthesis of methyl 2,3,5-tri-O-benzyl-a-d-arabinofuranosyl-(1!5)-2,3-
di-O-benzyl-a-d-arabinofuranoside (32):[56] The disaccharide 32 was pre-
pared from the thioarabinofuranoside 23 (199 mg, 0.378 mmol) and the
thioarabinofuranosyl acceptor 27 (100 mg, 0.29 mmol) by the LCG proce-
dure as described for the synthesis of 29. The crude reaction mixture
(after workup) was concentrated for flash chromatography over silica gel
(elution: EtOAc/hexane 1:3) to give 32 as a colorless oily substance
Synthesis of 2,3-di-O-benzyl-5-O-(tert-butyldiphenylsilyl)-a-d-arabinofur-
anosyl-(1!5)-2,3-di-O-benzoylthio-a-d-arabinofuranoside (29):
A mix-
ture of the thioarabinofuranoside 22 (1.89 g, 2.8 mmol), the thioarabino-
furanosyl acceptor 25 (1 g, 2.16 mmol), and activated molecular sieves
(26 g) in a dry CH2Cl2/CH3CN/EtCN mixture (1:2:1, 216 mL) was stirred
under N2 from RT to ꢁ708C for 30 min. NIS (0.63 mg, 2.8 mmol) and
TMSOTf (125 mL, 0.63 mmol) were added, followed by stirring at ꢁ708C
for 0.5 h. The reaction was then quenched with Et3N (0.1 mL), a few
(173 mg, a/b 9:1, 80%). a-Anomer: Rf =0.5 (EtOAc/hexane 3:7); [a]D27
=
+50.1 (c=1.6 in CHCl3); 1H NMR (CDCl3, 300 MHz): d=7.30–7.24 (m,
25H; Ar), 5.17 (s, 1H; H-1), 4.92 (s, 1H; H-1), 4.60–4.40 (m, 10H), 4.27–
4.15 (m, 2H), 4.07–3.99 (m, 3H), 3.94–3.86 (m, 2H), 3.73–3.64 (m, 1H),
3.62–3.54 (m, 2H), 3.37 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3):
12200
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 12193 – 12202