R.G. Soengas, A.M. Estévez / Ultrasonics Sonochemistry 19 (2012) 916–920
919
with mixtures of ethyl acetate/hexane as eluents to give the pure
compounds 5.
4.6. 3-O-[2-(Benzyloxyamino)pent-4-enoyl]-1,2:5,6-di-O-
isopropylidene- -glucofuranose (11)
a-D
To a suspension of indium powder (40.3 mg, 0.35 mmol) in THF
(1 mL) was added allyl bromide (0.05 mL, 0.52 mmol) and the mix-
ture was sonicated for 10 min. The oxime 10 (0.15 g, 0.35 mmol) was
added and sonication was continued for a further 4 h. The reaction
mixture was neutralized with saturated aqueous sodium hydrogen
carbonate, diluted with water (10 mL) and extracted with ether
(3 ꢀ 25 mL). The combined organic layers were dried over magne-
sium sulfate, filtered and the solvent was evaporated in vacuo. The
residue was purified by flash column chromatography (ethyl ace-
tate/hexane 2:9) to give 3-O-[2(R)-(benzyloxyamino)pent-4-
4.3. Diethyl 2-(benzyloxyamino)-3-methylsuccinate (5a)
Purification by flash column chromatography (EtOAc/Hex 1:9
1:8) to yield 5a (125.3 mg, 81%). Data for the syn isomer:
Rf = 0.28 (ethyl acetate/hexane 1:9). mmax (neat)/cmꢁ1 3251 (NH),
1742 (CO), 1739 (CO). 1HNMR (300 MHz, CDCl3): 1.20–1.29 (m,
9H, 3ꢀ –CH3), 3.34–3.36 (m, 1H, H-3), 4.07–4.28 (m, 5H), 4.59
(ABq, 2H, –OCH2Ph), 5.72 (bs, 1H, –NH–), 7.19–7.32 (m, 5H, Ar–
H). 13CNMR (75 MHz, CDCl3): 11.5 (–CH3), 14.1 (–CH3), 34.2
(–CH–), 61.5 (–CH2–), 61.7 (–CH2–), 65.7 (–CH–), 76.7 (–CH2–),
128.1, 128.5, 129.1 (5ꢀ –CH–), 135.5 (–C–), 171.1, 172.5 (2ꢀ C@O).
Data for the anti isomer: Rf = 0.29 (ethyl acetate/hexane 1:8). mmax
(neat)/cmꢁ1 3248 (NH), 1740 (CO), 1738 (CO). 1HNMR (300 MHz,
CDCl3): 1.22–1.29 (m, 9H, 3ꢀ –CH3), 3.34–3.38 (m, 1H, H-3),
4.06–4.29 (m, 5H), 4.57 (ABq, 2H, –OCH2Ph), 5.72 (bs, 1H, –NH–),
7.17–7.32 (m, 5H, Ar–H). 13CNMR (75 MHz, CDCl3): 11.2 (–CH3),
14.1 (–CH3), 34.3 (–CH–), 61.3 (–CH2–), 61.6 (–CH2–), 65.8
(–CH–), 77.0 (–CH2–), 127.8, 128.5, 129.0 (5ꢀ –CH–), 135.7 (–C–),
171.5, 173.0 (2ꢀ C@O). m/z (CI) 310 [(MH)+, (66%)]; HRMS calcu-
lated for C16H24NO5: 310,1654. Found 310.1660.
enoyl]-1,2:5,6-di-O-isopropylidene-
41%) and 3-O-[2(S)-(benzyloxyamino)pent-4-enoyl]-1,2:5,6-di-O-
isopropylidene- -glucofuranose 11b (50 mg, 31%). Data for 11a:
a-D-glucofuranose 11a (65 mg,
a-D
Rf = 0.29 (ethyl acetate/hexane 2:9). mmax (neat)/cmꢁ1 3230 (NH),
3030 (CH), 2950 (CH), 1740 (CO). 1HNMR (300 MHz, CDCl3): 1.25
(s, 3H, –CH3), 1.26 (s, 3H, –CH3), 1.41 (s, 3H, –CH3), 1.51 (s, 3H,
–CH3), 2.25–2.49 (m, 2H), 3.65–3.73 (m, 1H), 3.98–4.02 (m, 1H),
4.12–4.21 (m, 3H), 4.44 (d, 1H, J = 6.4 Hz), 4.71 (s, 2H, –OCH2Ph),
5.02–5.18 (m, 2H), 5.27 (d, 1H, J = 2.2 Hz), 5.69–5.78 (m, 2H), 5.89
(bs, 1H), 7.29–7.41 (m, 5H, Ar–H). 13CNMR (75 MHz, CDCl3): 25.4,
26.4, 26.6, 27.1 (4ꢀ –CH3), 33.0 (–CH2–), 51.1 (–CH–), 61.5
(–CH2–), 65.7 (–CH–), 73.3 (–CH–), 76.8 (–CH2–), 77.5 (–CH–), 79.4
(–CH–), 82.7 (–CH–), 105.8 (–CH–), 108.9, 112.8 (2ꢀ –C–), 116.5
(–CH2), 125.2, 128.2, 128.5, 129.0 (5ꢀ –CH–), 134.4 (–CH–), 135.7
(–C–), 171.6 (C@O). Data for 11b: Rf = 0.25 (ethyl acetate/hexane
2:9). 1HNMR (300 MHz, CDCl3): 1.24 (s, 3H, –CH3), 1.26 (s, 3H,
–CH3), 1.43 (s, 3H, –CH3), 1.50 (s, 3H, –CH3), 2.27–2.48 (m, 2H),
3.65–3.74 (m, 1H), 3.89–4.24 (m, 4H), 4.32 (d, 1H, J = 6.4 Hz), 4.72
(s, 2H, –OCH2Ph), 5.04–5.12 (m, 2H), 5.28 (s, 1H), 5.69–5.79 (m,
2H), 5.85 (bs, 1H), 7.31–7.42 (m, 5H, Ar–H). 13CNMR (75 MHz,
CDCl3): 25.5, 26.4, 26.8, 27.3 (4ꢀ –CH3), 33.0 (–CH2–), 53.0 (–CH–),
61.5 (–CH2–), 65.6 (–CH–), 73.5 (–CH–), 76.2 (–CH–), 77.0 (–CH2–),
78.5 (–CH–), 81.5 (–CH–), 105.3 (–CH–), 109.3, 112.8 (2ꢀ –C–),
117.0 (–CH2), 127.2, 128.0, 128.4, 129.0 (5ꢀ –CH–), 134.4 (–CH–),
135.2 (–C–), 172.1 (C@O). m/z (CI) 464 [(MH)+, (58%)]; HRMS calcu-
lated for C24H33NO8: 464.2284. Found: 464.2288.
4.4. Diethyl 2-(benzyloxyamino)-3-phenylsuccinate (5b)
Purification by flash column chromatography (EtOAc/Hex 1:9
1:8) to yield the syn isomer (59%) and the anti isomer (29%). Data
for the syn isomer: Rf = 0.30 (ethyl acetate/hexane 1:9). mmax
(neat)/cmꢁ1 3220 (NH), 1739 (CO), 1688 (CO). 1HNMR (300 MHz,
CDCl3): 1.25–1.30 (m, 6H, 2ꢀ –OCH2CH3), 4.05–4.29 (m, 6H), 4.53
(ABq, 2H, –OCH2Ph), 5.81 (bs, 1H, –NH–), 7.17–7.42 (m, 10H,
Ar–H). 13CNMR (75 MHz, CDCl3): 13.5, 13.8 (2ꢀ –CH3), 43.8
(–CH–), 60.8, 61.0 (2ꢀ –CH2–), 66.2 (–CH–), 75.8 (–CH2–), 127.2,
128.1, 128.2, 128.4, 128.5, 128.8, 129.0, 129.1 (10ꢀ –CH–), 133.6,
137.4 (2ꢀ –C–), 171.9, 174.0 (2ꢀ C@O). Data for the anti isomer:
Rf = 0.29 (ethyl acetate/hexane 1:8). mmax (neat)/cmꢁ1 3225 (NH),
1740 (CO), 1687 (CO). 1HNMR (300 MHz, CDCl3): 1.21 (t, 3H,
–OCH2CH3), 1.28 (t, 3H, –OCH2CH3), 4.02–4.29 (m, 6H), 4.51
(ABq, 2H, –OCH2Ph), 5.76 (bs, 1H, –NH–), 7.18–7.42 (m, 10H,
Ar–H). 13CNMR (75 MHz, CDCl3): 13.8, 14.0 (2ꢀ –CH3), 41.9
(–CH–), 61.3 (–CH2–), 65.6 (–CH–), 77.1 (–CH2–), 127.5, 128.1,
128.3, 128.4, 128.5, 128.8, 129.1, 129.5 (10ꢀ –CH–), 134.8, 136.7
(2ꢀ –C–), 171.3, 173.7 (2ꢀ C@O). m/z (CI) 372 [(MH)+, (47%)];
HRMS calculated for C21H26NO5: 372.1811. Found: 372.1815.
4.7. 3-O-[3-(Ethoxycarbonyl)-2-(benzyloxyamino)-3-
phenylpropanoyl]-1,2:5,6-di-O-isopropylidene-a-D-glucofuranose
(12)
To a suspension of indium powder (46.0 mg, 0.39 mmol) in THF
(1 mL) was added ethyl 2-phenylacetate (0.1 mL, 0.59 mmol) and
the mixture was sonicated for 10 min. The oxime 10 (0.16 g,
0.39 mmol) was added and sonication was continued for a further
7 h. The reaction mixture was neutralized with saturated aqueous
sodium hydrogen carbonate, diluted with water (10 mL) and ex-
tracted with ether (3 ꢀ 25 mL). The combined organic layers were
dried over magnesium sulfate, filtered and the solvent was
evaporated in vacuo. The residue was purified by flash column
chromatography (ethyl acetate/hexane 1:5) to give 3-O-[3-(ethoxy-
carbonyl)-2-(benzyloxyamino)-3-phenylpropanoyl]-1,2:5,6-di-O-
4.5. (2S,3R)/(2R,3S)-3-Methylaspartic acid 7
To a degassed solution of diester 5a (50 mg, 0.16 mmol) in
methanol and two drops of 1 M aqueous solution of hydrochloric
acid, palladium black was added and the mixture was stirred at
r.t. under hydrogen atmosphere for 14 h. After filtering over a celite
pad, the filtrate was evaporated in vacuo to give the crude amine 6,
which was used in the next step without any further purification.
To a solution of the amine in dioxane/water 1:1 (mL), barium
hydroxide was added (83.34 mg, 0.48 mmol) and the mixture
was heated at 50 °C for 12 h. After cooling to r.t., a DOWEX 50 W
resin was added to pH 4 and the mixture was stirred for 1 h. Then,
the resin was filtered, washed with water until no reaction with
silver nitrate was observed and stirred with 1 M aqueous solution
of ammonium hydroxide. After 2 h., the resin was filtered off and
isopropylid ene-a-D-glucofuranose 12 (78 mg, 34%). Rf = 0.30
(ethyl acetate/hexane 1:5). mmax (neat)/cmꢁ1 3345 (NH), 1728
(CO), 1739 (CO); 1HNMR (300 MHz, CDCl3): 1.22–1.51 (m, 15H,
5ꢀ –CH3), 3.82–4.75 (m, 9H), 4.49–4.52 (m, 3H) 5.78 (d, 1H,
J = 3.7 Hz), 7.15–7.48 (m, 10H, Ar–H). 13CNMR (75 MHz, CDCl3)
(major isomer): 14.1 (–CH3), 25.4, 26.4, 26.6, 27.1 (4ꢀ –CH3), 50.8
(–CH–), 61.5 (–CH2–), 65.7 (–CH–), 67.7 (–CH2–), 72.3 (–CH–),
76.8 (–CH2–), 77.0 (–CH–), 79.9 (–CH–), 83.2 (–CH–), 105.3
(–CH–), 109.5, 112.5 (2ꢀ –C–), 125.2, 128.1, 128.2, 128.4, 128.5,
128.8, 129.0, 129.1 (10ꢀ –CH–), 135.4, 137.3 (2ꢀ –C–), 170.7,
the filtrate evaporated under reduced pressure to give
7
(30.69 mg, 62%). 1HNMR (300 MHz, D2O): 1.01 (d, 3H, J = 7.6 Hz),
2.90–2.99 (m, 1H), 3.88 (d, 1H, J = 3.3 Hz); 13C NMR (75 MHz,
D2O): 11.2 (–CH3), 51.7 (–CH–), 61.0 (–CH–), 172.9 (–C@O).