Carbasugar Analogues of Galactofuranosides
J3,4 = 8.6 Hz, 1 H, 3-H), 3.90–3.96 (m, 2 H, 1-H, 5-H), 4.01 (ddd, 2.19 (m, 2 H, 4I-H, 4II-H), 3.44–4.02 (m, 12 H, 1I-H, 2I-H, 3I-H,
J2,3 = 5.2, J1,2 = 3.7, J2,4a = 1.0 Hz, 1 H, 2-H), 4.48, 4.58 (2ϫ d, J
= 11.8 Hz, 2 H, PhCH2), 4.51, 4.55 (2ϫ d, J = 12.0 Hz, 2 H,
PhCH2), 4.54, 4.69 (2ϫ d, J = 11.7 Hz, 2 H, PhCH2), 4.58, 4.67
5I-H, 6I-H, 6ЈI-H, 1II-H, 2II-H, 3II-H, 5II-H, 6II-H, 6ЈII-H), 4.35 (d,
J = 11.6 Hz, 1 H, PhCHHЈ), 4.41–4.69 (m, 12 H, 5 ϫ PhCH2,
PhCHHЈ, PhCHHЈ), 4.76 (d, J = 11.7 Hz, 1 H, PhCHHЈ), 7.25–
(2ϫ d, J = 11.7 Hz, 2 H, PhCH2), 7.27–7.38 (m, 20 H, Ar-H) ppm. 7.37 (m, 35 H, Ar-H) ppm. 13C NMR (125 MHz, CDCl3): δC
=
13C NMR (100 MHz, CDCl3): δC = 28.2 (t, C-4a), 43.5 (d, C-4), 27.2, 27.9 (2ϫ t, C-4aI, C-4aII), 41.5, 44.0 (2ϫ d, C-4I, C-4II), 70.9,
70.3 (d, C-5), 70.8, 72.0, 72.3, 73.4 (4ϫ t, 4ϫ PhCH2), 73.5 (t, C-
6), 81.2 (d, C-1), 84.5 (d, C-3), 89.5 (d, C-2), 127.6, 127.6, 127.7,
127.7, 127.8, 127.8, 127.9, 127.9, 128.4, 128.4, 128.5 (11ϫ d, Ar-
CH), 138.0, 138.3, 138.4 (3ϫ s, Ar-C) ppm. HRMS calcd. for
C35H38O5Na [MNa+] 561.2611; found 561.2595.
72.0, 72.1, 72.4, 72.6, 73.0, 73.4, 73.8, 74.0 (9ϫ d, C-6I, C-6II, 7ϫ
PhCH2), 77.3, 78.0, 81.2, 82.2, 83.9, 84.4, 86.2, 89.8 (8ϫ d, C-1I,
C-2I, C-3I, C-5I, C-1II, C-2II, C-3II, C-5II), 127.5, 127.6, 127.6,
127.7, 127.7, 127.8, 127.8, 127.9, 128.0, 128.1, 128.2, 128.2, 128.3,
128.4, 128.4, 128.5, 128.5, 128.7 (18ϫ d, Ar-CH), 137.2, 128.4,
138.4, 138.5, 138.5, 139.0, 139.1 (7ϫ s, 7 ϫ Ar-C) ppm. HRMS
calcd. for C63H68O9Na [MNa+] 991.4756; found 991.4718.
The regioisomeric alcohol 9 was also isolated (7 mg, 2%) as an oil.
3,5,6-Tri-O-benzyl-4a-carba-β-
D-galactofuranosyl-(1Ǟ6)-1,2,3,5-
The descriptor “x” refers to an unspecified one of the carbasugars
“I” or “II”; “y” refers to the other one.
tetra-O-benzyl-4a-carba-β- -galactofuranose (14): Epoxide 6
D
(31 mg, 0.072 mmol) and alcohol 9 (150 mg, 0.279 mmol) were dis-
solved in CH2Cl2 (0.75 mL) under N2 at room temp. BF3·Et2O
(18 μL, 0.14 mmol) was dissolved in dry CH2Cl2 (2.5 mL) and
125 μL (7 μmol BF3·Et2O) of this solution was transferred to the
colourless reaction mixture, which instantly turned pale yellow. Af-
ter 10 min, TLC (toluene/EtOAc, 5:1) showed complete consump-
tion of epoxide (Rf = 0.8) and formation of a major product (Rf =
0.5) as well as remaining alcohol (Rf = 0.4). The reaction was
quenched by addition of Et3N (0.5 mL) and the mixture was con-
centrated in vacuo. The crude product was purified by flash column
chromatography (toluene/EtOAc, 4:1) to give the pseudodisaccha-
ride 14 (48 mg, 69%) as a colourless oil. [α]2D5 = –55.2 (c = 1.0,
CHCl3). 1H NMR (400 MHz, CDCl3): δH = 1.58, 1.79 (2ϫ m, 2
H, 4aI-H, 4aII-H), 1.90–2.03 (m, 2 H, 4aЈI-H, 4aЈII-H), 2.24, 2.36
(2ϫ m, 2 H, 4I-H, 4II-H), 3.41–4.07 (m, 12 H, 1I-H, 2I-H, 3I-H, 5I-
H, 6I-H, 6ЈI-H 1II-H, 2II-H, 3II-H, 5II-H, 6II-H, 6ЈII-H), 4.36–4.73
(m, 14 H, 7ϫ PhCH2), 7.25–7.34 (m, 35 H, Ar-H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 26.8, 27.6 (2ϫ t, C-4aI, C-4aII), 42.7, 43.0
(2ϫ d, C-4I, C-4II), 71.0, 71.5, 72.1, 72.2, 72.5, 73.0, 73.0, 73.5 (8ϫ
t, C-6I, C-6II, 7ϫ PhCH2), 77.4, 81.3, 82.5, 83.8, 83.9, 84.0, 90.1
(7 ϫ d, C-1I, C-2I, C-3I, C-5I, C-1II, C-2II, C-3II, C-5II), 127.6,
127.7, 127.7, 127.7, 127.9, 127.9, 128.0, 128.1, 128.1, 128.2, 128.3,
128.4, 128.4, 128.5, 128.5, 128.5 (16ϫ d, Ar-CH), 138.4, 138.5,
138.5, 138.6, 138.9, 138.9, 138.9 (7ϫ s, 7 ϫ Ar-C) ppm. HRMS
calcd. for C63H68O9Na [MNa+] 991.4756; found 991.4745.
General Procedure for Acetylation: The alcohol was dissolved in a
mixture of Ac2O and pyridine, and stirred at room temp. After
TLC (toluene/EtOAc, 8:1) showed complete consumption of start-
ing material and formation of a single product (typically up to 3 h),
the reaction mixture was concentrated by co-evaporating all solvent
with toluene (2ϫ 10 mL). The residue was purified by flash column
chromatography to give the acetate.
2-O-Acetyl-3,5,6-tri-O-benzyl-4a-carba-β-
D-galactofuranosyl-
(1Ǟ6)-1,2,3,5-tetra-O-benzyl-4a-carba-β- -galactofuranose (16):
D
Pseudodisaccharide 14 (49 mg, 0.050 mmol) was converted with
Ac2O/pyridine [1:1] (2 mL) and DMAP (1 mg, 0.008 mmol) into its
acetate 16 (42 mg, 84%), an oil (Rf = 0.3, pentane/EtOAc, 3:1),
according to the general procedure. [α]2D5 = –38.1 (c = 1.0, CHCl3).
1
IR (film): ν = 1733 (C=O) cm–1. H NMR (400 MHz, CDCl ): δ
˜
3
H
= 1.79 (m, 2 H, 4aI-H, 4aII-H), 1.90 (ddd, J1,4aЈ = 5.8, J4,4a = 11.1,
J4a,4aЈ = 13.5 Hz, 1 H, 4aЈII-H), 2.01 (s, 3 H, CH3), 2.04 (m, 1 H,
4aЈI-H), 2.30 (ddat, J = 3.1, J = 9.5, Jat = 8.8 Hz, 1 H, 4I-H), 2.44
(ddat, J = 3.4, Jat = 8.0, J4,4a = 11.2 Hz, 1 H, 4II-H), 3.49 (dd, J =
3.7, J = 10.0 Hz, 1 H, 6-H), 3.52 (dd, J = 4.5, J = 10.0 Hz, 1 H,
6-H), 3.59 (dd, J = 6.5, J = 10.0 Hz, 1 H, 6Ј-H), 3.65 (m, 1 H, 1II-
H), 3.67 (dd, J = 6.9, J = 10.0 Hz, 1 H, 6Ј-H), 3.74 (m, 2 H, 5I-H,
5II-H), 3.81 (dd, J = 4.0, J = 8.1 Hz, 1 H, 3II-H), 3.86 (dd, J2,3
=
6.1, J3,4 = 8.8 Hz, 1 H, 3I-H), 3.91 (dat, J = 7.2, Jat = 3.9 Hz, 1 H,
1I-H), 4.00 (at, J = 4.9 Hz, 1 H, 2I-H), 4.33 (d, J = 11.8 Hz, 1 H,
PhCHHЈ), 4.34 (d, J = 11.7 Hz, 1 H, PhCHHЈ), 4.38 (d, J =
11.7 Hz, 1 H, PhCHHЈ), 4.45 (d, J = 11.6 Hz, 1 H, PhCHHЈ), 4.46
(d, J = 11.8 Hz, 1 H, PhCHHЈ), 4.50 (d, J = 12.1 Hz, 1 H,
PhCHHЈ), 4.52–4.56 (m, 2 H, PhCHHЈ, PhCHHЈ), 4.57 (d, J =
11.8 Hz, 1 H, PhCHHЈ), 4.58–4.64 (m, 2 H, 2ϫ PhCHHЈ), 4.68
(d, J = 11.8 Hz, 1 H, PhCHHЈ), 4.75 (d, J = 11.7 Hz, 1 H,
PhCHHЈ), 4.76 (d, J = 11.7 Hz, 1 H, PhCHHЈ), 5.22 (m, 1 H, 2II-
H), 7.25–7.36 (m, 35 H, Ar-H) ppm. 13C NMR (100 MHz, CDCl3):
δC = 21.3 (q, CH3), 27.4 (t, C-4aI), 29.0 (t, C-4aII), 43.4 (d, C-4I),
45.2 (d, C-4II), 71.0, 72.1, 72.3, 73.1, 73.2, 73.5 (6ϫ t, 7ϫ PhCH2,
C-6I, C-6II), 77.0, 77.4 (2ϫ d, C-5I, C-5II), 81.4, 81.8 (2ϫ d, C-1II,
C-2II), 82.7 (C-1I), 83.9, 84.3 (2ϫ d, C-3I, C-3II), 90.0 (d, C-2I),
127.9, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.4, 128.5, 128.5,
128.5 (11ϫ d, Ar-CH), 138.4, 138.4, 138.6, 138.7, 138.8, 139.1,
139.2 (7ϫ s, 7 ϫ Ar-C), 170.0 (s, C=O) ppm. HRMS calcd. for
C65H70O10Na [MNa+] 1033.4861; found 1033.4838.
Also formed was the pseudotrisaccharide resulting from attack of
the pseudodisaccharide alcohol on a second molecule of epoxide
(7 mg, ca. 14%), but this compound could not be obtained com-
pletely pure. HRMS calcd. for C91H98O13Na [MNa+] 1421.7055;
found 1421.6900.
3,5,6-Tri-O-benzyl-4a-carba-β-
D-galactofuranosyl-(1Ǟ5)-1,2,3,6-
tetra-O-benzyl-4a-carba-β- -galactofuranose (15): Epoxide 6
D
(52 mg, 0.121 mmol) and alcohol 13 (261 mg, 0.485 mmol) were
dissolved in CH2Cl2 (0.75 mL) at room temp. under N2. BF3·Et2O
(20 μL, 0.158 mmol) was dissolved in dry CH2Cl2 (4 mL), and
306 μL (12 μmol BF3·Et2O) of this solution was transferred to the
colourless reaction mixture, which instantly turned pale yellow. Af-
ter 10 min, TLC (toluene/EtOAc, 5:1) showed complete consump-
tion of epoxide (Rf = 0.8) and formation of a major product (Rf =
0.3) as well as remaining alcohol (Rf = 0.2). The reaction was
quenched by addition of Et3N (1 mL) and the mixture was concen-
trated in vacuo. The crude product was purified by flash column
chromatography (pentane/EtOAc, 3:1) to give pseudodisaccharide
15 (61 mg, 52%) as an oil. [α]2D5 = –44.8 (c = 1.0, CHCl3). IR (film):
2-O-Acetyl-3,5,6-tri-O-benzyl-4a-carba-β-
D-galactofuranosyl-
(1Ǟ5)-1,2,3,6-tetra-O-benzyl-4a-carba-β- -galactofuranose (17):
D
Pseudodisaccharide 15 (29 mg, 0.030 mmol) was converted with
Ac2O/pyridine (3 mL) and DMAP (1 mg, 0.008 mmol) into its acet-
ate 17 (31 mg, 99%), an oil (Rf = 0.7, toluene/EtOAc, 6:1), accord-
ν = 3436 (OH) cm–1. 1H NMR (400 MHz, CDCl ): δH = 1.58 (ddd,
˜
3
J = 7.7, J = 11.3, J4a,4aЈ = 13.3 Hz, 1 H, 4ay-H), 1.71 (m, 1 H, 4ax-
H), 1.84 (ddd, J = 6.7, J = 10.7, J4a,4aЈ = 13.5 Hz, 1 H, 4aЈx-H),
ing to the general procedure. [α]2D5 = –61.2 (c = 1.0, CHCl3). IR
2.03 (ddd, J = 6.5, J = 8.9, J4a,4aЈ = 13.6 Hz, 1 H, 4aЈy-H), 2.09– (film): ν = 1736 (C=O) cm–1. H NMR (400 MHz, CDCl ): δ
=
1
˜
3
H
Eur. J. Org. Chem. 2011, 1367–1375
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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