P. Díaz Pérez, M. I. García-Moreno, C. Ortiz Mellet, J. M. García Fernández
FULL PAPER
H-8), 4.22 (ddd, J8a,1b = 6.3, J8a,1a = 9.0 Hz, 1 H, H-5), 4.34 (dd, δ = 1.25, 1.42 (2 s, 6 H, CMe2), 2.01 (s, 3 H, MeCO), 4.05 (dd, J3,4
J1a,1b = 9.0 Hz, 1 H, H-1b), 4.47 (t, 1 H, H-1a) ppm. 13C NMR = 3.8, J4,5 = 7.1 Hz, 1 H, H-4), 4.13 (m, 1 H, H-5), 4.15 (dd, J5,6b
(125.7 MHz, D2O): δ = 54.9 (C-8a), 66.7 (C-1), 69.8 (C-6), 71.1 (C- = 5.7, J6a,6b = 6.9 Hz, 1 H, H-6b), 4.49 (m, 1 H, H-6a), 4.68 (d,
8), 71.5 (C-7), 76.9 (C-5), 160.5 (CS) ppm. CIMS: m/z (%) = 206 J2,3 = 5.9 Hz, 1 H, H-2), 4.78 (dd, 1 H, H-3), 5.75 (br. s, 1 H, NH),
(5) [M + H]+. C7H11NO6 (205.27): C 40.98, H 5.40, N 6.83; found
C 40.90, H 5.47, N 6.78.
6.11 (s, 1 H, H-1) ppm. 13C NMR (125.7 MHz, CDCl3): δ = 20.8
(MeCO), 24.3, 25.7 (CMe2), 52.2 (C-5), 66.3 (C-6), 78.8 (C-3), 83.3
(C-4), 85.0 (C-2), 100.2 (C-1), 113.6 (CMe2), 158.9 (CO carba-
mate), 169.1 (CO ester) ppm. FABMS: m/z (%) = 283 (30) [M +
H]+. C12H17O7N (287.28): C 50.17, H 5.96, N 4.87; found C 50.07,
H 5.85, N 4.75.
(5R,6R,7S,8S,8aR)-5,6,7,8-Tetraacetoxy-3-thioxo-2-oxaindolizidine
(37): Conventional acetylation of 8 (46 mg, 0.21 mmol) gave 37.
Yield: 67 mg (82%). Rf = 0.54 (2:1 EtOAc/petroleum ether). [α]2D2
= +74.5 (c = 1.0, CH2Cl2). UV (CH2Cl2): λ = 249.6 nm (ε = 17.3).
IR (NaCl): ν
= 2999, 2920, 1752, 1752, 1553, 1371, 1212,
˜
max
(5R,6S,7S,8R,8aS)-5,6,7,8-Tetrahydroxy-3-thioxo-2-oxaindolizidine
(10): Compound 40 (90 mg, 0.31 mmol) was deacetalated by treat-
ment with 90% TFA/water (5 mL). The reaction mixture was con-
centrated and the residue coevaporated several times with water
to eliminate traces of acid. The resulting residue was subjected to
conventional acetylation with Ac2O/pyridine (1:1, 1.6 mL) and the
peracetylated mixture was purified by column chromatography
using 100:1 CH2Cl2/MeOH as eluent. The resulting crude peracety-
lated mixture of furanose and indolizidine isomers, according to
NMR, was deacetylated with methanolic NaOMe to give 10 as the
only reaction product. Yield: 34 mg (50 %). Rf = 0.45 (45:5:3
1077 cm–1. H NMR (300 MHz, CDCl3): δ = 2.02–2.20 (4 s, 12 H,
4 MeCO), 4.21 (t, J1a,1b = J8a,1b = 8.5 Hz, 1 H, H-1b), 4.50 (td,
J8,8a = 1.8, J8a,1a = 8.5 Hz, 1 H, H-8a), 4.61 (t, 1 H, H-1a), 5.31
(dd, J7,8 = 2.6, J6,7 = 10.7 Hz, 1 H, H-7), 5.39 (dd, J5,6 = 3.8 Hz,
1 H, H-6), 5.53 (dd, 1 H, H-8), 7.23 (d, 1 H, H-5) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 20.2–20.5 (MeCO), 55.1 (C-8a), 65.2 (C-
6), 66.7 (C-8), 67.3 (C-1), 67.7 (C-7), 75.4 (C-5), 168.2–170.0 (CO),
186.6 (CS) ppm. FABMS: m/z (%) = 412 (100) [M + Na]+.
C15H19NO9S (389.39): C 46.27, H 4.92, N 3.60; found C 46.55, H
4.67, N 3.59.
1
EtOAc/EtOH/H2O). [α]2D2 = +77 (c = 1.0, H2O). UV (CH2Cl2): λ =
(5R,6R,7S,8S,8aR)-5,6,7,8-Tetraacetoxy-3-oxo-2-oxaindolizidine
(38): Conventional acetylation of 9 (25 mg, 0.12 mmol) gave 38.
Yield: 38 mg (85%). Rf = 0.42 (2:1 EtOAc/petroleum ether). [α]2D2
1
247nm (ε = 10.8). H NMR (500 MHz, D2O): δ = 3.97 (dd, J6,7
=
3.4, J5,6 = 4.4 Hz, 1 H, H-6), 4.06 (dd, J4,5 = 1.9, J7,8 = 3.4 Hz, 1
H, H-8), 4.13 (t, 1 H, H-7), 4.63 (dd, J8a,1b = 6.7, J1a,1b = 9.0 Hz,
1 H, H-1b), 4.70 (ddd, J8a,1a = 9.0 Hz, 1 H, H-8a), 4.79 (t, 1 H, H-
1a), 5.86 (d, 1 H, H-5) ppm. 13C NMR (125.7 MHz, D2O): δ =
55.4 (C-8a), 66.6 (C-6), 70.9 (C-8), 71.4 (C-1), 73.7 (C-7), 81.2 (C-
5), 189.5 (CS) ppm. FABMS: m/z (%) = 222 (60) [M + H]+.
C7H11O5NS (221.24): C 38.00, H 5.01, N 6.33; found C 37.68, H
4.69, N 6.33.
= +59.6 (c = 1.0, CH Cl ). IR (NaCl): ν = 2999, 2928, 1752,
˜
max
2
2
1537, 1371, 1212, 1077 cm–1. 1H NMR (300 MHz, CDCl3): δ =
2.00–2.20 (4 s, 12 H, 4 MeCO), 4.02 (dd, J8a,1b = 5.9, J1a,1b
=
8.5 Hz, 1 H, H-1b), 4.32 (ddd, J8,8a = 1.7, J8a,1a = 8.5 Hz, 1 H, H-
8a), 4.41 (t, 1 H, H-1a), 5.29 (dd, J7,8 = 2.3, J6,7 = 10.9 Hz, 1 H,
H-7), 5.34 (dd, J5,6 = 3.5 Hz, 1 H, H-6), 5.49 (dd, 1 H, H-8), 6.78
(d, 1 H, H-5) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 20.0–20.4
(MeCO), 51.3 (C-8a), 65.5 (C-6), 67.2 (C-8), 67.8 (C-7), 62.7 (C-1),
72.8 (C-5), 154.1 (CO carbamate), 168.4, 169.2, 169.9, 170.1 (CO
ester) ppm. FABMS: m/z (%) = 396 (100) [M + Na]+. C15H19NO10
(373.32): C 48.26, H 5.13, N 3.75; found C 48.15, H 4.95, N 3.74.
(5R,6S,7S,8R,8aS)-5,6,7,8-Tetrahydroxy-3-oxo-2-oxaindolizidine
(11): Compound 41 (90 mg, 0.31 mmol) was deacetalated by treat-
ment with 90% TFA/water (5 mL). The reaction mixture was con-
centrated and the residue coevaporated several times with water
to eliminate traces of acid. The resulting residue was subjected to
conventional acetylation with Ac2O/pyridine (1:1, 2.6 mL) and the
peracetylated mixture was purified by column chromatography
using 100:1 CH2Cl2/MeOH as eluent. The resulting crude peracety-
lated mixture of furanose and indolizidine isomers, according to
NMR, was deacetylated with methanolic NaOMe to give 11 as the
only reaction product. Yield: 32 mg (50 %). Rf = 0.28 (45:5:3
EtOAc/EtOH/H2O). [α]2D2 = +52 (c = 1.0, MeOH). 1H NMR
(300 MHz, D2O): δ = 3.92 (dd, J6,7 = 3.2, J5,6 = 4.5 Hz, 1 H, H-
6), 4.00 (dd, J8,8a = 1.8, J7,8 = 4.2 Hz, 1 H, H-8), 4.09 (t, 1 H, H-
7), 4.40 (dd, J8a,1b = 8.6, J1a,1b = 8.6 Hz, 1 H, H-1b), 4.48 (ddd,
J8a,1a = 7.5 Hz, 1 H, H-8a), 4.57 (t, 1 H, H-6a), 5.34 (d, 1 H, H-
1) ppm. 13C NMR (75.5 MHz, D2O): δ = 48.8 (C-8a), 64.4 (C-1),
64.5 (C-6), 68.2 (C-8), 71.4 (C-7), 75.2 (C-5), 158.6 (CO) ppm.
CIMS: m/z (%) = 206 (30) [M + H]+. C7H11O6N (205.17): C 40.98,
H 5.40, N 6.83; found C 41.03, H 5.40, N 6.65.
1-O-Acetyl-5-amino-5-deoxy-2,3-O-isopropylidene-β-L-gulofuranose
5,6-Cyclic Thiocarbamate (40): Thiocarbonylation of 1-O-acetyl-5-
amino-5-deoxy-2,3-O-isopropylidene-β-l-gulofuranose 39 (201 mg,
0.87 mmol) by treatment with CS2/DCC for 8 h, as above described
for the preparation of 14, followed by purification by column
chromatography (1:2 Ǟ 2:1 EtOAc/petroleum ether) gave 40. Yield:
185 mg (70%). Rf = 0.33 (1:1 EtOAc/petroleum ether). [α]2D2 = +73
(c = 1.0, CH2Cl2). UV (CH2Cl2): λ = 249 nm (ε = 22.4). IR (KBr):
ν
= 3330, 2988, 1742, 1505, 1466, 1379, 1265, 1094 cm–1. 1H
˜
max
NMR (500 MHz, CDCl3): δ = 1.26, 1.45 (2 s, 6 H, CMe2), 2.04 (s,
3 H, MeCO), 4.13 (dd, J3,4 = 4.0, J4,5 = 7.3 Hz, 1 H, H-4), 4.32
(ddd, J5,6b = 6.5, J5,6a = 9.5 Hz, 1 H, H-5), 4.45 (dd, J6a,6b = 9.5 Hz,
1 H, H-6b), 4.71 (d, J2,3 = 5.9 Hz, 1 H, H-2), 4.76 (t, 1 H, H-6a),
4.82 (dd, 1 H, H-3), 6.13 (s, 1 H, H-1), 7.51 (br. s, 1 H, NH) ppm.
13C NMR (125.7 MHz, CDCl3): δ = 20.9 (MeCO), 24.3, 25.7
(CMe2), 56.2 (C-5), 71.8 (C-6), 78.8 (C-3), 82.4 (C-4), 84.9 (C-2),
100.0 (C-1), 113.8 (CMe2), 169.2 (CO), 189.6 (CS) ppm. FABMS:
m/z (%) = 326 (100) [M + Na]+. C12H17O6NS (303.34): C 47.51, H
5.65, N 4.62; found C 47.60, H 5.53, N 4.67.
(5R,6S,7S,8R,8aS)-5,6,7,8-Tetraacetoxy-3-thioxo-2-oxaindolizidine
(42): Conventional acetylation of 10 (35 mg, 0.16 mmol) gave 42.
Yield: 54 mg (87%). Rf = 0.53 (70:1 CH2Cl2/MeOH). [α]2D2 = –50.4
1-O-Acetyl-5-amino-5-deoxy-2,3-O-isopropylidene-β-
L
-gulofuranose
(c = 1.0, CH Cl ). IR (KBr): ν
= 2988, 1750, 1371, 1227,
˜
2
2
max
1
5,6-Cyclic Carbamate (41): Carbonylation of 39 (211 mg,
0.81 mmol) by treatment with triphosgene/diisopropyl ethylamine
for 45 min, as described for the preparation of 15, and purification
by column chromatography (1:1 EtOAc/petroleum ether Ǟ EtOAc)
yielded 41. Yield: 100 mg (43%). Rf = 0.24 (3:1 EtOAc/petroleum
1094 cm–1. H NMR (500 MHz, CDCl3): δ = 2.00–2.17 (4 s, 12 H,
4 MeCO), 4.23 (m, 1 H, H-1b), 4.64 (m, 2 H, H-8a, H-1a), 5.14
(dd, J8,8a = 2.0, J7,8 = 4.0 Hz, 1 H, H-8), 5.29 (t, J6,7 = 4.0 Hz, 1
H, H-7), 5.36 (t, J5,6 = 4.0 Hz, 1 H, H-6), 7.14 (d, 1 H, H-5) ppm.
13C NMR (125.7 MHz, CDCl3): δ = 20.4–20.7 (MeCO), 52.8 (C-
8a), 64.4 (C-1), 66.0 (C-6), 66.8 (C-7), 67.6 (C-8), 74.8 (C-5), 168.3–
169.6 (CO ester), 187.2 (CS) ppm. FABMS: m/z (%) = 412 (100)
ether). [α]2D2 = +78 (c = 1.0, CH Cl ). IR (KBr): νmax = 3405, 2955,
˜
2
2
1753, 1537, 1414, 1238, 1094 cm–1. 1H NMR (500 MHz, CDCl3):
2912
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 2903–2913