Glycosylation of Cyclitols: Synthesis of Neamine-Type Aminoglycosides
FULL PAPER
ν˜ ϭ 3030, 2970, 2922, 2102, 1740, 1541, 1365, 1354, 1229, 1217,
(C6Ј), 49.7, 48.4 (NBn), 29.4 (C5). ESI-MS: m/z ϭ 1195.6 [M ϩ
1
1159, 1072. H NMR (CDCl3, 400 MHz): δ ϭ 8.03Ϫ8.01 (m, 1 H, Na]ϩ.
Harom), 7.66Ϫ6.94 (m, 28 H, Harom), 6.87Ϫ6.83 (m, 2 H, Harom),
1-D-(1,4,6/2,3)-1-(4,6-Diazido-2,3-di-O-benzyl-4,6-dideoxy-α-D-
6.54 (d, J ϭ 7.3 Hz, 1 H, Harom), 6.01 (ddd, J ϭ 2.5, J ϭ 5.1, J ϭ
10.0 Hz, 1 H, CϭCH), 5.57 (d, J ϭ 10.2 Hz, 1 H, CϭCH), 5.09
(d, J ϭ 3.4 Hz, 1 H, H1Ј), 4.97Ϫ4.93 (m, 2 H, 2 ϫ benzylic H),
4.92Ϫ4.84 (m, 2 H, 1 benzylic H, H4), 4.80Ϫ4.74 (m, 2 H, 3 ϫ
benzylic H), 4.62Ϫ4.58 (m, 2 H, 2 ϫ benzylic H), 4.44Ϫ4.38 (m, 2
H, 2 ϫ benzylic H), 4.11Ϫ4.07 (m, 2 H, H1, H6), 3.83 (t, J ϭ
9.3 Hz, 1 H, H3Ј), 3.74, (ddd, J ϭ 2.5, J ϭ 5.1, J ϭ 9.8 Hz, 1 H,
H5Ј), 3.56 (dd, J ϭ 3.3, J ϭ 9.9 Hz, 1 H, H2Ј), 3.48 (t, J ϭ 9.3 Hz,
1 H, H4Ј), 3.33 (dd, J ϭ 2.5, J ϭ 13.0 Hz), 1 H, C6Ј-Ha) 3.25 (dd,
J ϭ 5.2, J ϭ 13.0 Hz, 1 H, C6ЈϪHb), 2.12Ϫ2.04 (m, 1 H, C5ϪHa),
1.96Ϫ1.92 (m, 1 H, C5ϪHb). 13C NMR (CDCl3, 100 MHz): δ ϭ
147.6, 147.0, 138.2, 137.9, 137.6, 136.5, 134.8, 133.8 (Cq arom),
133.4, 132.7, 131.3, 129.0, 127.3, 126.9, 124.2, 123.6 (CHarom, C2,
C3), 99.3 (C1Ј), 81.0, 80.1, 78.6, 77.9 (C1, C2Ј, C3Ј, C4Ј), 75.4,
75.3, 73.6 (CH2 OBn), 70.8 (C5Ј), 56.9, 56.0 (C4, C6), 51.4, 49.9,
49.0 (C6Ј, CH2 NBn), 28.7 (C5). ESI-MS: m/z ϭ 1158.7 [M ϩ
Na]ϩ.
glucopyranosyl)-4,6-bis[benzyl(o-nitrophenylsulfonyl)amino]cyclo-
hexane-1,2,3-triol (25): Yield: 903 mg (88%). Off-white foam.
[α]2D0 ϭ Ϫ4.4 (c ϭ 0.5, CHCl3). IR (neat): ν˜ ϭ 3026, 2970, 2104,
1738, 1541, 1365, 1352, 1161, 1088, 1013. 1H NMR (CDCl3,
400 MHz): δ ϭ 8.14Ϫ8.12 (m, 1 H, Harom), 7.74Ϫ6.98 (m, 25 H,
Harom), 6.78 (d, J ϭ 7.3 Hz, 2 H, Harom), 4.97 (d, J ϭ 10.7 Hz, 1
H, benzylic H), 4.91 (d, J ϭ 3.1 Hz, 1 H, H1Ј), 4.87Ϫ4.81 (m, 3
H, benzylic H), 4.75 (d, J ϭ 11.8 Hz, 1 H, benzylic H), 4.54Ϫ4.44
(m, 4 H, H6, 3 benzylic H), 4.19Ϫ4.17 (m, 1 H, H4), 4.06 (br. s, 1
H, H2), 3.82 (br. s, 1 H, H1), 3.61Ϫ3.53 (m, 3 H, H2Ј, H3, H3Ј),
3.42Ϫ3.37 (m, 2 H, H4Ј, C6ЈϪHa), 3.32Ϫ3.26 (m, 2 H, H5Ј,
C6ЈϪHb), 2.92 (br. s, 1 H, OH) 2.69 (d, J ϭ 5.2 Hz, 1 H, OH),
1.74Ϫ1.68 (m, 2 H, H5). 13C NMR (CDCl3, 100 MHz): δ ϭ 147.5,
147.1, 137.4, 137.23, 137.18, 137.0 (CHarom), 133.9, 133.0 (CHarom),
132.6 (CHarom), 132.2, 131.6, 131.4, 131.2, 128.9, 128.0, 127.1,
124.4, 123.8 (CHarom), 100.0 (C1Ј), 85.8 (C1), 79.4 (C2Ј), 78.8
(C3Ј), 75.4, 73.7 (CH2 OBn), 70.8 (C5Ј), 70.3 (C2), 67.6 (C3), 62.4
(C4Ј), 56.9 (C4), 53.4 (C6), 51.7 (C6Ј), 49.7, 48.5 (CH2 NBn), 29.8
(C5). ESI-MS: m/z ϭ 1128.6 [M ϩ Na]ϩ.
(1R,4R,6S)-1-(4,6-Diazido-2,3-di-O-benzyl-4,6-dideoxy-α-D-
glucopyranosyl)-4,6-bis[benzyl(o-nitrophenylsulfonyl)amino]cyclo-
hex-2-enol (23): Yield: 1.65 g (77%), α/β ϭ 5.0:1. Off-white foam.
Spectroscopic data for α-anomer: [α]2D0 ϭ ϩ8.4 (c ϭ 0.5, CHCl3).
IR (neat): ν˜ ϭ 3030, 2970, 2924, 2876, 2104, 1740, 1541, 1366,
1350, 1157. 1H NMR (CDCl3, 400 MHz): δ ϭ 8.04 (d, J ϭ 8.6 Hz,
1 H, Harom), 7.68Ϫ7.10 (m, 24 H, Harom), 6.98 (t, J ϭ 7.3 Hz, 1 H,
1-O-(6-Amino-6-deoxy-α-D-glucopyranosyl)-(1S,2S,3R)-cyclohex-4-
ene-1,2,3-triol (26): Yield: 26 mg (52%). 1H NMR (D2O, 400 MHz):
δ ϭ 5.87Ϫ5.82 (m, 1 H, CϭCH), 5.64 (br. d, J ϭ 10.1 Hz, 1 H,
CϭCH), 5.17 (d, J ϭ 3.8 Hz, 1 H, H1Ј), 4.43 (br. s, 1 H, H3),
4.20Ϫ4.19 (m, 1 H, H2), 4.10Ϫ4.02 (m, 2 H, H1, H5Ј), 3.82 (t, J ϭ
9.5 Hz, 1 H, H3Ј), 3.63 (dd, J ϭ 3.9, J ϭ 9.8 Hz, 1 H, H2Ј), 3.49
(dd, J ϭ 2.9, J ϭ 13.3 Hz, 1 H, C6ЈϪHa), 3.40 (t, J ϭ 9.5 Hz, 1
H, H4Ј), 3.22 (dd, J ϭ 8.5, J ϭ 13.3 Hz, 1 H, C6ЈϪHb), 1054Ϫ2.47
(m, 1 H, C6ϪHa), 2.32Ϫ2.24 (m, 1 H, C6ϪHb). 13C NMR (CDCl3,
100 MHz): δ ϭ 127.8, 127.0 (C4, C5), 97.0 (C1Ј), 75.2, 73.4, 72.2,
71.9, 71.2, 68.7, 68.6 (C2Ј, C3Ј, C4Ј, C5Ј, C1, C2, C3), 41.3 (C6Ј),
Harom), 6.87 (t, J ϭ 7.6 Hz, 1 H, Harom), 6.57 (d, J ϭ 7.4 Hz, 1 H,
Harom), 5.98 (ddd, J ϭ 2.4, J ϭ 5.0, J ϭ 10.0 Hz, 1 H, CϭCH),
5.61 (d, J ϭ 10.2 Hz, 1 H, CϭCH), 5.11 (d, J ϭ 3.2 Hz, 1 H, H1Ј),
4.96Ϫ4.84 (m, 3 H, 2 ϫ benzylic H, H4), 4.81Ϫ4.74 (m, 3 H, 3 ϫ
benzylic H), 4.59 (d, J ϭ 16.3 Hz, 1 H, 1 benzylic H NBn),
4.44Ϫ4.35 (m, 2 H, 2 ϫ benzylic H NBn), 4.12Ϫ4.09 (m, 2 H, H1,
H6), 3.73 (t, J ϭ 9.3 Hz, 1 H, H3Ј), 3.60Ϫ3.46 (m, 3 H, H2Ј, H4Ј,
H5Ј), 3.39 (dd, J ϭ 2.2, J ϭ 13.1 Hz, 1 H, C6ЈϪHa), 3.33 (dd, J ϭ
4.9, J ϭ 13.1 Hz, 1 H, C6ЈϪHb), 2.35Ϫ1.98 (m, 2 H, H5). 13C
NMR (CDCl3, 100 MHz): δ ϭ 147.6, 147.0, 137.63, 137.56, 137.4,
126.4, 134.8 (Cq arom), 133.7, 133.5, 132.7, 131.7, 131.2, 131.1,
130.7, 127.6, 127.0, 124.3, 123.7 (CHarom, C2, C3), 99.4 (C1Ј), 80.0
(C2Ј), 78.8 (C3Ј), 78.2 (C1), 75.4, 73.6 (CH2 OBn), 69.9 (C5Ј), 62.7
(C4Ј), 57.0 (C4), 56.0 (C6), 51.8 (C6Ј), 49.9, 49.1 (CH2 NBn),
28.8 (C5).
ϩ
26.6 (C6). HRMS: found [M ϩ H]ϩ 292.1367 ppm; C12H22NO7
requires 292.1390.
1-O-(4,6-Diamino-4,6-dideoxy-α-D-glucopyranosyl)-(1S,2S,3R)-
cyclohex-4-ene-1,2,3-triol (27): Yield: 44 mg (67%). 1H NMR (D2O,
400 MHz): δ ϭ 5.88Ϫ5.83 (m, 1 H, CϭCH), 5.69Ϫ5.65 (m, 1 H,
CϭCH), 5.27 (d, J ϭ 3.7 Hz, 1 H, H1Ј), 4.49Ϫ4.41 (m, 2 H, H3,
H5Ј), 4.20Ϫ4.19 (m, 1 H, H2), 4.15Ϫ4.11 (m, 1 H, H1), 4.03 (t,
J ϭ 9.9 Hz, 1 H, H3Ј), 3.74 (dd, J ϭ 3.7, J ϭ 9.8 Hz), 1 H, H2Ј3.56
(dd, J ϭ 2.9, J ϭ 13.4 Hz, 1 H, C6ЈϪHa), 3.34Ϫ3.26 (m, 2 H,
H4Ј, C6ЈϪHb), 2.56Ϫ2.48 (m, 1 H, C6ϪHa), 2.35Ϫ2.28 (m, 1 H,
C6ϪHb). 13C NMR (CDCl3, 100 MHz): δ ϭ 127.7, 127.0 (C4, C5),
96.9 (C1Ј), 74.5, 71.9, 71.0, 69.2, 68.3, 65.6 (C2Ј, C3Ј, C5Ј, C1, C2,
C3), 54.3 (C4Ј), 40.9 (C6Ј), 26.9 (C6). HRMS: found [M ϩ H]ϩ
1-D-(1,4,6/2,3)-1-(6-Azido-2,3,4-tri-O-benzyl-6-deoxy-α-D-gluco-
pyranosyl)-4,6-bis[benzyl(o-nitrophenylsulfonyl)amino]cyclo-
hexane-1,2,3-triol (24):[20] Yield: 1.15 g (99%). Off-white foam.
[α]2D0 ϭ Ϫ33 (c ϭ 0.5, CHCl3). IR (neat): ν˜ ϭ 3020, 2901, 2102,
1740, 1541, 1350, 1161, 1070. 1H NMR (CDCl3, 400 MHz): δ ϭ
8.17Ϫ8.14 (m, 1 H, Harom), 7.74Ϫ6.89 (m, 31 H, Harom), 6.78 (d,
J ϭ 7.4 Hz, 1 H, Harom), 5.02 (d, J ϭ 10.9 Hz, 1 H, benzylic H),
4.96 (d, J ϭ 11.0 Hz, 1 H, benzylic H), 4.90Ϫ4.77 (m, 5 H, 4
benzylic H, H1Ј), 4.59 (d, J ϭ 11.0 Hz, 1 H, benzylic H), 4.56Ϫ4.50
(m, 2 H, 2 benzylic H), 4.44Ϫ4.40 (m, 2 H, 1 benzylic H, H6),
4.14Ϫ4.07 (m, 2 H, H2, H4), 3.80 (br. s, 1 H, H1), 3.74Ϫ3.69 (m,
1 H, H3Ј), 3.57 (br. s, 1 H, H3), 3.53 (dd, J ϭ 3.6, J ϭ 10.0 Hz, 1
H, H2Ј), 3.43Ϫ3.37 (m, 2 H, H4Ј, H5Ј), 3.31 (br. d, J ϭ 12.9 Hz,
1 H, H6Јa), 3.21 (dd, J ϭ 5.3, J ϭ 13.0 Hz, 1 H, H6Јb), 2.56 (br. s,
ϩ
291.1539 ppm; C12H23N2O6 requires 291.1556.
1-O-(3,6-Diamino-3,6-dideoxy-α-D-glucopyranosyl)-(1S,2S,3R)-
cyclohex-4-ene-1,2,3-triol (28): Yield: 24 mg (57%). 1H NMR (D2O,
400 MHz): δ ϭ 5.87Ϫ5.82 (m, 1 H, CϭCH), 5.65 (br. d, J ϭ
10.1 Hz, 1 H, CϭCH), 4.45 (br. s, 1 H, H3), 4.23Ϫ4.22 (m, 1 H,
H2), 4.16Ϫ4.10 (m, 2 H, H1, H5Ј), 3.91 (dd, J ϭ 3.7, J ϭ 10.7 Hz,
1 H, H2Ј), 3.67 (t, J ϭ 9.8 Hz, 1 H, H4Ј), 3.59Ϫ3.52 (m, 2 H, H3Ј,
C6ЈϪHa), 3.23 (dd, J ϭ 9.1, J ϭ 13.3 Hz, 1 H, C6ЈϪHb), 2.57Ϫ2.50
(m, 1 H, C6ϪHa), 2.33Ϫ2.26 (m, 1 H, C6ϪHb). 13C NMR (CDCl3,
100 MHz): δ ϭ 127.8, 126.9 (C4, C5), 95.7 (C1Ј), 74.2, 71.1, 68.8,
68.63, 68.59, 68.5 (C2Ј, C4Ј, C5Ј, C1, C2, C3), 55.8 (C3Ј), 41.0
(C6Ј), 26.6 (C6). HRMS: found [M ϩ H]ϩ 291.1561 ppm;
2 H, OH), 1.77Ϫ1.68 (m, 1 H, H5a), 1.63Ϫ1.60 (m, 1 H, H5b). 13
C
NMR (CDCl3, 100 MHz): δ ϭ 147.6, 147.2, 138.0, 137.7, 137.3,
134.4 (Cq arom), 133.8, 133.0 (CHarom), 132.7 (Cq arom), 132.3,
131.9, 131.4, 127.0, 124.4, 123.9 (CHarom), 100.2 (C1Ј), 85.4 (C1),
81.0 (C3Ј), 79.5 (C2Ј), 78.2 (C4Ј), 75.5 (2 CH2 OBn), 73.9 (CH2 1-
OBn), 71.8 (C5Ј), 70.4 (C2), 67.6 (C3), 56.9 (C4), 53.3 (C6), 51.3
ϩ
C12H23N2O6 requires 291.1556.
D
-(1,4,6/2,3)-1-(6-Amino-6-deoxy-α-
D-glucopyranosyl)-4,6-
diaminocyclohexane-1,2,3-triol (29): A solution of compound 24
Eur. J. Org. Chem. 2004, 2404Ϫ2410
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2409