Synthesis of 1-Amino-1,2,5-trideoxy-2,5-imino-l-iditol
J4,5 = 7.9, J3,4 = 6.6 Hz, 1 H, 4-H), 3.80 (d, J2,3 = 4.4 Hz, 1 H, 2-
(5S,6R,7R,7aS)-5-Aminomethyl-6,7-dihydroxytetrahydropyrrolo-
H), 3.64 (dd, J3,4 = 6.6 Hz, J2,3 = 4.4 Hz, 1 H, 3-H), 1.68 (br. s, 2 [1,2-c]oxazol-3-one Hydrochloride (12): Carbamate 11 (100 mg,
H, NH2) ppm. 13C NMR (125 MHz, CDCl3, 20 °C): δ = 138.0 (C-
i 4-O-Bn), 137.9 (C-i 3-O-Bn), 133.9 (C-5), 128.6 (C-Ar), 128.6 (C-
Ar), 128.3 (C-Ar), 128.1 (C-Ar), 127.9 (C-Ar), 121.3 (C-1), 120.4
0.27 mmol) was dissolved in CHCl3 (4.5 mL) and transferred into
a Fischer-Porter bottle, EtOH (7.5 mL), HCl in diethyl ether
(1.4 mL, 2 m), and Pd(OH2)/C (230 mg) were then added, and the
(C-6), 82.1 (C-3 and C-4), 75.5 (CH2 3-O-Bn), 71.0 (CH2 4-O-Bn), vessel was charged with H2 (7 bar). The reaction mixture was
45.3 (C-2) ppm. HRMS (ESI): calcd. for [C20H22N2O2 + Na]+
345.1573; found 345.1573.
stirred vigorously at room temperature for 3 d. After releasing the
H2 pressure, the reaction mixture was filtered through a plug of
Celite, washing with EtOH and H2O, and concentrated in vacuo to
provide amine 12 as the HCl salt (50.1 mg, 0.26 mmol, 98%). Rf =
0.25 (DCM/MeOH/EtOH/30% aq. NH3, 5:2:2:1). [α]1D9 = –50.0 (c
(2S,3R,4R,5R)-3,4-Bisbenzyloxy-5-iodomethylpyrrolidine-2-carbo-
nitrile (10a): α-Aminonitrile syn-9a (30.0 mg, 0.09 mmol) was co-
evaporated with toluene and dissolved in DCM (450 μL) under a
nitrogen atmosphere. N-Iodosuccinimide (25.1 mg, 0.11 mmol) was
added, and the pink solution was stirred at room temperature for
5 h, over which time the solution became dark red in color. The
solution was quenched with sat. aq. Na2S2O3 and extracted with
EtOAc, and the organic layer was washed with H2O and brine,
dried (MgSO4), filtered, and concentrated in vacuo. The residue
was purified using silica gel gradient flash chromatography (PE/
EtOAc, 20:1 Ǟ 3:1) to give iodoiminosugar 10a as a pale orange
oil (31.3 mg, 0.07 mmol, 75%). Rf = 0.52 (PE/EtOAc, 2:1). [α]2D0.6
= 0.1, H O). IR (film): ν = 3928, 2925, 2854, 1727, 1642, 1404,
˜
2
1243, 1083, 1014, 783 cm–1. 1H NMR (500 MHz, D2O, HCl salt,
20 °C): δ = 4.64 (t, 2J6a,6b = 9.2 Hz, J5,6a = 8.9 Hz, 1 H, 6a-H), 4.52
2
(dd, J6a,6b = 9.2 Hz, J5,6b = 3.3 Hz, 1 H, 6b-H), 4.49 (dd, J2,3
4.4 Hz, J3,4 = 0.5 Hz, 1 H, 3-H), 4.36 (dt, J5,6a = 8.9 Hz, J5,6b
3.3, J4,5 Ͻ 1 Hz, 1 H, 5-H), 4.09 (br. s, 1 H, 4-H), 4.04 (dt, J1b,2
=
=
=
8.5 Hz, J2,3 = J1a,2 = 4.4 Hz, 1 H, 2-H), 3.30 (dd, 2J1a,1b = 13.4 Hz,
J1a,2 = 4.4 Hz, 1 H, 1a-H), 3.21 (dd, J1a,1b = 13.4 Hz, J1b,2
2
=
8.5 Hz, 1 H, 1b-H) ppm. 13C NMR (150 MHz, D2O, HCl salt,
20 °C): δ = 164.9 (C-7), 77.7 (C-3), 75.1 (C-4), 64.4 (C-6), 61.8 (C-
5), 58.8 (C-2), 39.3 (C-1) ppm. HRMS (ESI): calcd. for
[C7H12N2O4 + Na]+ 211.0689; found 211.0684.
= –21.0 (c = 1.0, CHCl ). IR (film): ν = 3336, 3062, 3030, 2922,
˜
3
2867, 2245, 1496, 1454, 1354, 1207, 1091, 1027, 913, 736, 697 cm–1.
1H NMR (500 MHz, CDCl3, 20 °C): δ = 7.39–7.28 (m, 10 H, H-
2
2
Ar), 4.66 (d, Ja,b = 11.8 Hz, 1 H, CHa 3-O-Bn), 4.59 (d, Ja,b
=
1-Amino-1,2,5-trideoxy-2,5-imino-L-iditol (3): A solution of NaOH
2
11.8 Hz, 1 H, CHb 3-O-Bn), 4.54 (d, Ja,b = 11.6 Hz, 1 H, CHa 4-
O-Bn), 4.51 (d, Ja,b = 11.6 Hz, 1 H, CHb 4-O-Bn), 4.27 (d, J4,5
in EtOH (0.5 mL, 2 m) was added to amino carbamate 12 (16.0 mg,
0.09 mmol) and stirred at reflux for 2 h. The resulting reaction mix-
ture was loaded directly onto a Dowex H+ ion-exchange resin col-
umn and washed with H2O to remove the excess amount of salt.
The hydrolyzed amine was then eluted with 30% aq. NH3 and con-
centrated in vacuo to provide amino hexitol 3 (13.5 mg, 0.08 mmol,
98%). Rf = 0.01 (DCM/MeOH/EtOH/30% aq. NH3, 5:2:2:1); (HCl
2
=
5.4 Hz, 1 H, 2-H), 4.09 (dd, J2,3 = 5.4 Hz, J3,4 = 2.7 Hz, 1 H, 3-
H), 4.03 (dd, J4,5 = 5.4 Hz, J3,4 = 2.7 Hz, 1 H, 4-H) 3.84 (dd, J5,6a,6b
2
= 7.3 Hz, J4,5 = 5.4 Hz 1 H, 5-H), 3.27 (dd, J6a,6b = 9.6 Hz, J5,6a
2
= 7.3 Hz, 1 H, 6a-H), 3.15 (dd, J6a,6b = 9.6 Hz, J5,6b = 7.3 Hz, 1
H, 6b-H), 2.32 (br. s, 1 H, NH) ppm. 13C NMR (125 MHz, CDCl3,
20 °C): δ = 137.3 (C-i 4-O-Bn), 136.8 (C-i 3-O-Bn), 128.8 (C-Ar),
128.7 (C-Ar), 128.5 (C-Ar), 128.3 (C-Ar), 128.3 (C-Ar), 128.1 (C-
Ar), 117.9 (C-1), 82.4 (C-3), 81.8 (C-4), 73.1 (CH2 3,4-O-Bn), 61.5
(C-5), 51.4 (C-2), 4.1 (C-6) ppm. HRMS (ESI): calcd. for
[C20H21IN2O2 + Na]+ 449.0720; found 449.0726.
salt) [α]2D6 = +6.0 (c = 1.0, H O). IR (film, free base): ν = 3376,
˜
2
2881, 2854, 1651, 1549, 1393, 1218, 1115, 1059, 946, 836 cm–1. H
1
NMR (500 MHz, 2% NaOD in D2O, 20 °C): δ = 4.14 (d, J2,3
=
4 Hz, J3,4 Ͻ 1 Hz, 1 H, 3-H), 4.09 (d, J4,5 = 4 Hz, J3,4 Ͻ 1 Hz, 1
2
H, 4-H), 3.73 (dd, J6a,6b = 11.2 Hz, J5,6a = 6.5 Hz, 1 H, 6a-H),
2
(5S,6R,7R,7aS)-6,7-Dibenzyloxy-3-oxotetrahydropyrrolo[1,2-c]oxaz-
ole-5-carbonitrile (11): To a solution of α-aminonitrile syn-9a
(34.0 mg, 0.11 mmol) in THF (0.4 mL) was added I2 (66.9 mg,
0.26 mmol), H2O (0.4 mL), and NaHCO3 (177 mg, 2.11 mmol).
The reaction mixture was stirred at room temperature for 20 h,
quenched by the addition of sat. aq. Na2S2O3, and extracted with
EtOAc. The organic layer was washed with H2O and brine, dried
(MgSO4), filtered, and concentrated in vacuo. Purification of the
residue using silica gel gradient flash chromatography (PE/EtOAc,
10:1 Ǟ 1:1) provided carbamate 11 as a colorless viscous oil
3.64 (dd, J6a,6b = 11.2 Hz, J5,6b = 6.5 Hz, 1 H, 6b-H), 3.35 (td,
J5,6a = J5,6b = 6.5 Hz, J4,5 = 4 Hz, 1 H, 5-H), 3.28 (td, J1a,2 = J1b,2
2
= 6.9 Hz, J2,3 = 4 Hz, 1 H, 2-H), 2.77 (dd, J1a,1b = 12.7 Hz, J1a,2
2
= 6.9 Hz, 1 H, 1a-H), 2.66 (dd, J1a,1b = 12.7 Hz, J1b,2 = 6.9 Hz, 1
H, 1b-H) ppm. 13C NMR (125 MHz, 2% NaOD in D2O, 20 °C):
δ = 77.3 (C-3), 77.0 (C-4), 61.1 (C-5), 59.9 (C-6), 40.1 (C-1) ppm.
HRMS (ESI): calcd. for [C6H14N2O3 + H]+ 163.1077; found
163.1077. 1H NMR (500 MHz, D2O, 2HCl salt, 20 °C): δ = 4.41
(dd, J2,3 = 3.4 Hz, J3,4 = 1.7 Hz, 1 H, 3-H), 4.40 (dd, J4,5 = 3.6 Hz,
J3,4 = 1.7 Hz, 1 H, 4-H), 4.17 (td, J1a,2 = J1b,2 = 6.8 Hz, J2,3
=
=
(32.6 mg, 0.09 mmol, 85%). Rf = 0.24 (PE/EtOAc, 2:1). [α]D20
=
3.4 Hz, 1 H, 2-H), 4.07 (ddd, J5,6a = 8.8 Hz, J5,6b = 4.6 Hz, J4,5
2
+23.7 (c = 1.0, CHCl ). IR (film): ν = 3064, 3032, 2925, 2872, 2254,
˜
3
3.6 Hz, 1 H, 5-H), 4.00 (dd, J6a,6b = 12.2 Hz, J5,6a = 4.6 Hz, 1 H,
1755, 1469, 1316, 1216, 1093, 1051, 1001, 814, 736, 698 cm–1. 1H
6a-H), 4.91 (dd, 2J6a,6b = 12.2 Hz, J5,6b = 8.8 Hz, 1 H, 6b-H), 3.58
2
2
NMR (500 MHz, CDCl3, 20 °C): δ = 7.43–7.32 (m, 8 H, H-Ar),
(dd, J1a,1b = 13.7 Hz, J1a,2 = 6.8 Hz, 1 H, 1a-H), 3.49 (dd, J1a,1b
= 13.7, J1b,2 = 6.8 Hz, 1 H, 1b-H) ppm. 13C NMR (125 MHz, D2O,
2HCl salt, 20 °C): δ = 74.5 (C-3), 74.2 (C-4), 63.8 (C-5), 58.2 (C-
2), 57.2 (C-6), 35.8 (C-1) ppm.
2
7.16 (m, 2 H, H-Ar), 4.75 (d, Ja,b = 12 Hz, 1 H, CHa 3-O-Bn),
2
4.76 (d, J2,3 = 5.2 Hz, 1 H, 2-H), 4.56 (d, Ja,b = 12 Hz, 1 H, CHb
3-O-Bn), 4.50 (d, 2Ja,b = 12.6 Hz, 1 H, CHa 4-O-Bn), 4.45 (t, 2J6a,6b
2
= 8.7 Hz, J5,6a = 8.2 Hz, 1 H, 6a-H), 4.38 (t, J6a,6b = 6.2 Hz, J5,6b
2
= 3.0 Hz, 1 H, 6b-H), 4.35 (d, Ja,b = 12.6 Hz, 1 H, CHb 4-O-Bn),
Supporting Information (see footnote on the first page of this arti-
4.27 (dt, J5,6a = 8.2 Hz, J5,6b = J4,5 = 3.0 Hz, 1 H, 5-H), 4.23 (dd,
J2,3 = 5.2 Hz, J3,4 = 1.0 Hz, 1 H, 3-H), 3.77 (dd, J4,5 = 3.0 Hz, J3,4
= 1.0 Hz, 1 H, 4-H) ppm. 13C NMR (125 MHz, CDCl3, 20 °C): δ
= 161.0 (C-7), 136.5 (C-i 4-O-Bn), 136.3 (C-i 3-O-Bn), 128.9 (C-
Ar), 128.9 (C-Ar), 128.7 (C-Ar), 128.6 (C-Ar), 128.3 (C-Ar), 127.9
(C-Ar), 115.4 (C-1), 81.6 (C-3), 79.9 (C-4), 73.8 (CH2 3-O-Bn), 72.0
(CH2 4-O-Bn), 63.2 (C-6), 61.3 (C-5), 53.2 (C-2) ppm. HRMS
(ESI): calcd. for [C21H20N2O2 + Na]+ 387.1315; found 387.1317.
1
cle): Copies of the H and 13C NMR spectra.
Acknowledgments
The authors would like to thank the Lotteries Health Research
Grant (B. L. S., M. S. M. T.) for financial assistance.
Eur. J. Org. Chem. 2011, 4008–4014
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4013