6
L. Guazzelli et al. / Carbohydrate Research xxx (2014) xxx–xxx
(m, 2H, ArH), 7.82 (m, 1H, ArH), 7.75 (m, 1H, ArH), 7.58 (dd, 1H,
ArH), 7.50 (m, 2H, ArH), 7.44 (m, 2H, ArH), 7.38–7.30 (m, 18H,
ArH), 5.53 (s, 1H, H-1), 5.16 (d, 1H, Jgem = 11.5 Hz, PhCH2), 5.10
(d, 1H, Jgem = 11.5 Hz, NAPCH2), 5.04 (d, 1H, Jgem = 11.0 Hz, PhCH2),
4.98 (d, 1H, Jgem = 11.0 Hz, PhCH2), 4.92 (d, 1H, Jgem = 10.5 Hz,
PhCH2), 4.85 (d, 1H, Jgem = 11.0 Hz, PhCH2), 4.78 (d, 1H, Jgem = 10.5 Hz,
PhCH2), 4.71–4.68 (m, 2H, 2 PhCH2), 4.64 (d, 1H, Jgem = 10.5 Hz,
mixture was concentrated and purified by silica gel flash column
chromatography (toluene–EtOAc, 100:0 ? 76:24) to give 12
(1.03 g, 90%); Rf 0.22 (toluene/EtOAc 6:1); [a] +38 (c 1.0, CHCl3);
D
1H NMR (500 MHz, CDCl3): d 7.82 (m, 3H, ArH), 7.76 (m, 1H,
ArH), 7.54 (dd, 1H, ArH), 7.46 (m, 2H, ArH), 7.40 (m, 2H, ArH),
7.33-7.25 (m, 18H, ArH), 5.43 (d ꢃ s, 1H, H-1), 5.15 (d, 1H,
Jgem = 10 Hz, PhCH2), 5.00–4.95 (m, 3H, PhCH2, NAPCH2), 4.86 (d,
1H, Jgem = 10.8 Hz, PhCH2), 4.82 (d, 1H, Jgem = 10.8 Hz, PhCH2),
4.75 (d, 1H, Jgem = 11 Hz, NAPCH2), 4.63 (m, 2H, PhCH2), 4.58 (d,
PhCH2), 4.60 (d, 1H, J1 ,2 = 8.0 Hz, H-10), 4.49 (dd ꢃ m, 1H, H-2),
0
0
4.04–3.96 (m, 4H, H-3, H-4, H5, H-6a0), 3.84 (dd, 1H, J5 ,6b = 5.5 Hz,
0
0
J6a ,6b = 11.5 Hz, H-6b0), 3.81–3.72 (m, 3H, H-30, H-6a, H-6b), 3.68
1H, Jgem = 11 Hz, PhCH2), 4.52 (d, 1H, J1 ,2 = 7.2 Hz, H-10), 4.36 (dd,
1H, J5,6a = 4.2 Hz, JH-6a,H-6b = 12 Hz, H-6a), 4.30–4.27 (m, 2H, H-2,
H-6b), 4.24–4.21 (m, 1H, H-5), 4.00 (dd ꢃ t, 1H, H-4), 3.96 (dd,
1H, J2,3 = 3.0 Hz, J3,4 = 9.6 Hz, H-3), 3.84 (m, 1H, H-6a0), 3.72 (m,
1H, H-6b0), 3.68–3.60 (m, 3H, H-20, H-30, H-40), 3.38 (m, 1H, H-50),
2.65–2.55 (m, 2H, SCH2CH3), 1.76 (m, 1H, OH), 1.71 (s, 3H, COCH3),
1.26 (t, 3H, SCH2CH3); 13C NMR (125 MHz, CDCl3): d 170.6 (CO),
138.6, 138.2, 138.1, 137.9, 135.1, 133.3, 133.1 (ArC), 129.0–125.9
(ArCH), 102.8 (C-10), 84.5 (C-30), 82.5 (C-1), 81.8 (C-20), 78.8 (C-3),
77.2 (C-40), 76.6 (C-2), 75.7 (PhCH2), 75.4 (C-50), 75.2, 75.1, 75.0
(3 ꢄ PhCH2), 74.3 (C-4), 71.3 (NAPCH2), 70.0 (C-5), 63.3 (C-6),
62.2 (C-60), 25.8 (SCH2CH3), 20.5 (COCH3), 15.0 (SCH2CH3); HRMS
(ESI): [M+Na]+ Calcd for C55H60O11NaS, 951.3754; found,
951.3758. Anal. Calcd for C55H60O11S: C, 71.10; H, 6.51; S, 3.45.
Found: C, 70.76; H, 6.42; S, 3.43.
0
0
0
0
(dd ꢃ t, 1H, J2 ,3 = 8.0 Hz, H-20), 3.60 (dd ꢃ t, 1H, J3 ,4 = J4 ,5 = 8.0 Hz,
H-40), 3.47–3.43 (m, 1H, H-50), 2.65–2.62 (m, 2H, SCH2CH3), 1.30 (t,
3H, SCH2CH3), 0.89 (s, 9H, (CH3)3C(CH3)2Si), 0.07, 0.04 (2 s, 6H,
(CH3)3C(CH3)2Si); 13C NMR (125 MHz, CDCl3): d 138.9, 138.7,
138.5, 135.7, 133.6, 133.4 (ArC), 128.7–126.0 (ArCH), 102.1 (C-10),
85.2 (C-30), 82.1 (C-1), 82.0 (C-20), 78.3 (C-3), 77.8 (C-40), 76.9
(C-50), 75.9, 75.4, 75.2, 75.1, 74.9, 74.8 (C-2, C-4, 4 ꢄ PhCH2), 72.3
(C-5), 70.5 (NAPCH2), 63.1 (C-60), 62.8 (C-6), 26.2 ((CH3)3C(CH3)2Si),
25.8 (SCH2CH3), 18.5 ((CH3)3C(CH3)2Si), 15.1 (SCH2CH3), ꢁ4.9
((CH3)3C(CH3)2Si), ꢁ5.0 ((CH3)3C(CH3)2Si); HRMS (ESI): [M+Na]+
Calcd for C59H72O10NaSSi, 1023.4513; found, 1023.4520; Anal.
Calcd for C59H72O10SSi: C, 70.77; H, 7.25; S, 3.20. Found: C, 70.62;
H, 7.33; S, 3.40.
0
0
0
0
0
0
1.8. Ethyl (2,3,4-tri-O-benzyl-6-O-tert-butyldimethylsilyl-b-
D-
glucopyranosyl)-(1 ? 2)-6-O-acetyl-4-O-benzyl-3-O-(2-
naphthalenylmethyl)-1-thio-a-D-mannopyranoside (11)
1.10. Ethyl (2,3,4-tri-O-benzyl-b-
(1 ? 2)-6-O-acetyl-4-O-benzyl-3-O-(2-methylnaphthalenyl)-1-
thio- -mannopyranoside (13)
D-glucopyranosyluronic acid)-
a-D
Ac2O (0.88 mL, 9.27 mmol) was added at 20 °C to a solution of
10 (1.16 g, 1.16 mmol) in dry pyridine (20 mL), and the mixture
was stirred for 3 h (TLC, toluene–EtOAc, 9:1). The reaction mixture
was concentrated, and the residue re-dissolved and co-evaporated
with toluene (3 ꢄ 50 mL). Purification by silica gel flash column
chromatography (toluene–EtOAc, 100:0 ? 85:15) gave 11 (1.19 g,
TEMPO (83 mg, 0.53 mmol) and BAIB (3.43 g, 10.63 mmol) were
added to a vigorously stirred mixture of 12 (1.0 g, 1.06 mmol) in
CH2Cl2/H2O (2:1, 60 mL) and the two-phase reaction mixture was
stirred at 20 °C for 5 h. The progress of the reaction was followed
by TLC (toluene/EtOAc/AcOH, 16:3:1). The reaction was quenched
by the addition of an aqueous solution of Na2S2O3 (10% aq).
The mixture was extracted with EtOAc and the organic layer
was dried over MgSO4 and concentrated. Purification by silica
gel flash column chromatography (toluene ? toluene–EtOAc,
95:5 ? 90:10 ? 85:15 ? toluene–EtOAc–AcOH, 16:3:1) gave 13
96%); Rf 0.53 (toluene/EtOAc 9:1); [
a]
D
+33 (c 1.0, CHCl3); 1H
NMR (500 MHz, CDCl3): d 7.85 (m, 2H, ArH), 7.79 (d, 1H, ArH),
7.73 (m, 1H, ArH), 7.59 (d, 1H, ArH), 7.49–7.45 (m, 4H, ArH),
7.38–7.27 (m, 18H, ArH), 5.51 (s, 1H, H-1), 5.20 (d, 1H, Jgem
=
10.5 Hz, PhCH2), 5.11 (d, 1H, Jgem = 12.0 Hz, NAPCH2), 5.03 (d, 1H,
Jgem = 11.0 Hz, PhCH2), 4.99 (d, 1H, Jgem = 11.0 Hz, PhCH2), 4.90 (d,
1H, Jgem = 11.5 Hz, PhCH2), 4.83 (d, 1H, Jgem = 10.5 Hz, PhCH2),
4.70–4.66 (m, 3H, NAPCH2, PhCH2), 4.57 (m, 2H, H-10, PhCH2),
4.46 (m, 1H, H-2), 4.38 (dd, 1H, J5,6a = 4.5 Hz, J6a,6b = 12.0 Hz, H-
6a), 4.29 (dd ꢃ d, 1H, H-6b), 4.22 (m, 1H, H-5), 4.04–3.95 (m, 3H,
(0.97 g, 97%); Rf 0.39 (toluene–EtOAc–AcOH, 16:3:1); [a] +23 (c
D
1.0, CHCl3); 1H NMR (500 MHz, CDCl3): d 7.79–7.73 (m, 4H, ArH),
7.49–7.44 (m, 3H, ArH), 7.35–7.24 (m, 20H, ArH), 5.36 (br s, 1H,
H-1), 5.01 (d, 1H, Jgem = 10 Hz, PhCH2), 4.94 (d, 1H, Jgem = 10.5 Hz,
PhCH2), 4.87 (m, 2H, PhCH2, NAPCH2), 4.76 (d, 1H, Jgem = 11 Hz,
PhCH2), 4.71 (d, 1H, Jgem = 11.5 Hz, PhCH2), 4.67–4.63 (m, 3H,
H-10, PhCH2), 4.60 (d, 1H, Jgem = 11 Hz, NAPCH2), 4.56 (d, 1H,
Jgem = 11.5 Hz, PhCH2), 4.35–4.26 (m, 3H, H-2, H-6a, H-6b), 4.22–
H-3, H-4, H-6a0), 3.82 (dd, 1H, J5 ,6b = 6.5 Hz, J6a ,6b = 11.5 Hz, H-
6b0), 3.73–3.67 (m, 2H, H-20, H-30), 3.57 (dd ꢃ t, 1H, H-40), 3.43
(m, 1H, H-50), 2.68–2.61 (m, 2H, SCH2CH3), 1.73 (s, 3H, COCH3),
1.29 (t, 3H, SCH2CH3), 0.88 (s, 9H, (CH3)3C(CH3)2Si), 0.05, 0.02 (2
s, 6H, (CH3)3C(CH3)2Si); 13C NMR (125 MHz, CDCl3): d 170.9 (CO),
138.9, 138.5, 138.4, 135.5, 133.5, 133.3 (ArC), 129.2-126.0 (ArCH),
102.5 (C-10), 85.2 (C-30), 82.4 (C-1), 82.1 (C-20), 78.3 (C-3), 77.8
(C-40), 76.9 (C-50), 75.9 (PhCH2), 75.4, 75.3, 75.3, 75.2 (C-2,
3 ꢄ PhCH2), 74.3 (C-4), 70.5 (NAPCH2), 70.1 (C-5), 63.7 (C-6), 63.2
(C-60), 26.2 ((CH3)3C(CH3)2Si), 25.9 (SCH2CH3), 20.7 (COCH3), 18.5
((CH3)3C(CH3)2Si), 15.2 (SCH2CH3), ꢁ4.9 ((CH3)3C(CH3)2Si), ꢁ5.0
((CH3)3C(CH3)2Si); HRMS (ESI): [M+Na]+ m/z Calcd for C61H74O11NaSSi,
1065.4619; found, 1065.4624; Anal. Calcd for C61H74O11SSi: C,
70.22; H, 7.15; S, 3.07. Found: C, 70.18; H, 7.20; S, 3.38.
0
0
0
0
4.19 (m, 1H, H-5), 4.07 (d, 1H, J4 ,5 = 7.5 Hz, H-50), 4.01 (dd ꢃ t,
1H, H-40), 3.95 (m, 2H, H-3, H-4), 3.69 (dd ꢃ t, 1H, H-30), 3.63
(dd ꢃ t, 1H, H-20), 2.63–2.52 (m, 2H, SCH2CH3), 1.75 (s, 3H, COCH3),
1.25 (t, 3H, SCH2CH3); 13C NMR (125 MHz, CDCl3): d 170.6 (CO),
170.0 (COOH), 138.2, 138.1, 137.8, 137.3, 134.6, 133.3, 133.1
(ArC), 128.8–126.1 (ArCH), 103.0 (C-10), 82.9 (C-30), 82.3 (C-1),
80.3 (C-20), 79.4 (C-40), 79.0 (C-3), 77.3 (C-2), 75.3, 75.2, 75.1
(3 ꢄ PhCH2), 74.6 (C-50), 74.3 (PhCH2), 74.1 (C-4), 71.8 (NAPCH2),
70.0 (C-5), 63.2 (C-6), 25.7 (SCH2CH3), 20.5 (COCH3), 14.9 (SCH2-
CH3); HRMS (ESI): [M+Na]+ Calcd for C55H58O12NaS, 965.3547;
found, 965.3520. Anal. Calcd for C55H58O12S: C, 70.04; H, 6.20; S,
3.40. Found: C, 69.49; H, 6.03; S, 3.56.
0
0
1.9. Ethyl (2,3,4-tri-O-benzyl-b-D-glucopyranosyl)-(1 ? 2)-6-O-
acetyl-4-O-benzyl-3-O-(2-naphthalenylmethyl)-1-thio-
mannopyranoside (12)
a-D
-
1.11. Ethyl [benzyl (2,3,4-tri-O-benzyl-b-
glucopyranosyl)uronate]-(1 ? 2)-6-O-acetyl-4-O-benzyl-3-O-(2-
methylnaphthalenyl)-1-thio- -mannopyranoside (14)
D-
a
-D
TBAF trihydrate (0.52 g, 1.65 mmol) was added to a solution of
11 (1.28 g, 1.23 mmol) in dry THF (50 mL) and the mixture was
stirred at 20 °C (TLC, toluene/EtOAc, 10:1). After 3 h, the reaction
Cesium carbonate (95 mg, 1.54 mmol) was added to a solution
of 13 (0.97 g, 1.03 mmol) in dry DMF (35 mL) at 20 °C. After