Hemeon and Bennet
245
ring hemiaminal 11 upon chromatography. 1H NMR
(CDCl3, 500 MHz) δ: 0.86 (t, 3H, J = 7.3 Hz, CH2CH3),
1.29–1.41 (m, 16H, CMe2 × 2, OCH2CH3, CHaHbCH3),
1.51–1.58 (m, 1H, CHaCHbCH3), 1.95 (s, 3H, COCH3),
2.82–2.88 (m, 1H, H-4), 3.78–3.83 (m, 3H, H-6, H-7, H-9a),
3.89–3.95 (m, 1H, H-8), 4.06–4.09 (m, 1H, H-9b), 4.23–
4.28 (m, 3H, OCH2CH3, H-5), 5.50 (d, 1H, J3,4 = 10.2 Hz,
H-3), 5.73 (d, 1H, J5,NH = 9.4 Hz, NH), 6.54 (s, 1H, OH).
13C NMR (CDCl3, 125 MHz) δ: 12.0 (CH2CH3), 14.1
(OCH2CH3), 23.4 (COCH3), 24.6 (CH2CH3), 25.3, 26.5,
27.2, 27.5 (C(CH3)2 × 2), 39.1 (C-4), 54.1 (OCH2CH3/C-5),
61.8 (OCH2CH3/C-5), 67.8 (C-9), 77.0 (C-8), 80.5 (C-6/C-
7), 80.7 (C-6/C-7), 109.6, 110.3 (C(CH3)2 × 2), 113.1 (C-3),
142.3 (C-2), 164.4, 170.1 (C=O × 2).
(CDCl3, 125 MHz) δ: 14.0 (CH3CH2O), 21.3 (4-CH3), 22.6
(COCH3), 25.1, 26.8 (× 2), 27.0 (C(CH3)2 × 2), 33.0 (C-4),
43.0 (C-3), 61.8 (CH3CH2O), 67.6 (C-5), 68.2 (C-9), 77.5
(C-8), 78.8 (C-7), 83.0 (C-6), 90.8 (C-2), 109.8, 110.1
(C(CH3)2 × 2), 171.4, 171.7 (C=O × 2). Anal. calcd. for
C20H33NO8: C 57.82, H 8.01, N 3.37; found: C 57.52, H
7.90, N 3.59.
Minor anomer
1H NMR (CDCl3, 500 MHz) δ: 1.23 (d, 3H, JCH3,4
=
7.5 Hz, 4-CH3), 1.30 (t, 3H, J = 7.1 Hz, CH3CH2O), 1.34,
1.37, 1.42, 1.44 (s, 12H, C(CH3)2 × 2), 1.97 (d, 1H, J3a,3b
=
12.5 Hz, H-3a), 2.14 (s, 3H, COCH3), 2.50–2.60 (m, 2H, H-
3b, H-4), 3.57 (t, 1H, J6,7 + J7,8 = 17.0 Hz, H-7), 3.95 (s, 1H,
H-5), 3.98 (dd, 1H, J8,9a = 4.9 Hz, J9a,9b = 8.8 Hz, H-9a),
4.04–4.08 (m, 1H, H-8), 4.17–4.30 (m, 4H, H-6, H-9b,
CH3CH2O), 4.47 (s, 1H, OH). 13C NMR (CDCl3, 125 MHz)
δ: 14.0 (CH3CH2O), 21.4 (4-CH3), 22.1 (COCH3), 25.0,
26.8, 26.90, 26.93 (C(CH3)2 × 2), 31.9 (C-4), 45.0 (C-3),
62.0 (CH3CH2O), 67.6 (C-5), 68.1 (C-9), 77.6 (C-8), 78.8
(C-7), 83.1 (C-6), 90.0 (C-2), 109.8, 110.6 (C(CH3)2 × 2),
170.5 (COCH3), 171.8 (C-1).
Ethyl N-acetyl-5-amino-3,4,5-trideoxy-4-ethyl-6,7:8,9-di-
O-isopropylidene-D-glycero-D-talo-non-2-ulofuranosonate
(11)
The crude enol 10 was purified via flash chromatography
(hexanes–EtOAc gradient solvent system from 2:1 to 1:2
v/v) to afford the hemiaminal 11 as a colorless syrup
(134 mg, 0.31 mmol, 53%). IR (cm–1): 1648 (amide C=O),
1
1747 (ester C=O), 3490 (OH). H NMR (CDCl3, 500 MHz)
Ethyl 5-acetamido-2,7-anhydro-3,4,5-trideoxy-4-ethyl-D-
glycero-D-talo-non-2-ulopyranosonate (14)
δ: 0.97 (t, 3H, J = 7.4 Hz, CH2CH3), 1.25 (t, 3H, J = 7.1 Hz
OCH2CH3), 1.34, 1.35, 1.40, 1.41 (s, 12H, C(CH3)2 × 2),
1.65–1.71 (m, 2H, CH2CH3), 1.89 (d, 1H, J3a,3b = 13.2 Hz,
H-3a), 2.14–2.19 (m, 4H, COCH3, H-4), 2.62 (ddd, 1H,
J3a,3b = 13.2 Hz, J3b,4 = 7.6 Hz, J3b,OH = 1.6 Hz, H-3b), 3.47
4-Ethyl hemiaminal 11 (239 mg, 0.557 mmol) was dis-
solved in trifluoroacetic acid (4.0 mL) to which water
(0.4 mL) was added. The resulting solution was stirred at
room temperature for 15 h and was then concentrated under
reduced pressure to give a dark brown syrup (249 mg) that
was used directly in the next reaction. A sample for charac-
terization could be purified by flash chromatography
(EtOAc–MeOH–H2O gradient solvent system from 20:3:1 to
10:3:1 v/v/v), giving the 2,7-anhydro-4-ethylsialoside 14 as a
light brown foamy syrup. IR (cm–1): 1645 (amide C=O),
(t, 1H, J6,7 = J7,8 = 8.5 Hz, H-7), 3.93 (dd, 1H, J8,9a
5.8 Hz, J9a,9b = 8.7 Hz, H-9a), 4.04 (dt, 1H, J7,8 + J8,9a
=
+
J8,9b = 20.8 Hz, H-8), 4.12 (s, 1H, H-5), 4.14–4.26 (m, 4H,
H-9b, H-6, OCH2CH3), 4.87 (d, 1H, J3b.OH = 1.5 Hz, OH).
13C NMR (CDCl3, 100 MHz) δ: 12.6 (CH2CH3), 14.0
(OCH2CH3), 22.5 (COCH3), 25.1, 26.6, 26.8, 27.0 (C(CH3)2 ×
2), 27.3 (CH2CH3), 40.5 (C-4), 41.1 (C-3), 61.7 (OCH2CH3),
65.3 (C-5), 68.5 (C-9), 77.5 (C-8), 78.9 (C-7), 83.4 (C-6),
90.6 (C-2), 109.8, 110.2 (C(CH3)2 × 2), 171.4, 171.8 (C=O
× 2).
1
1746 (ester C=O), 3328 (OH). H NMR (D2O, 600 MHz) δ:
0.82 (t, 3H, J = 7.4 Hz, CH2CH3), 1.24–1.33 (m, 5 H,
CH2CH3, OCH2CH3), 1.65 (t, 1H, J3a,3b = J3a,4 = 13.1 Hz, H-
3a), 2.02–2.06 (m, 4H, H-3b, COCH3), 2.12–2.17 (m, 1H,
H-4), 3.52–3.58 (m, 2H, H-8, H-9a), 3.71 (br d, 1H, J9a,9b
=
Ethyl N-acetyl-5-amino-3,4,5-trideoxy-6,7:8,9-di-O-
isopropylidene-4-methyl-D-glycero-D-talo-non-2-
ulofuranosonate (13)
Enone 5 (1.02 g, 2.56 mmol) was reacted with dimethyl-
zinc (2.0 mol/L in toluene, 1.9 mL, 3.8 mmol) to generate
the 4-methyl hemiaminal 13 (1.4:1.0 anomeric ratio,
373 mg, 0.898 mmol, 35%) using the methods reported ear-
lier for the synthesis of the ethyl-addition product 10. The
major anomer of 13 was purified to analytical standards for
complete characterization.
11.5 Hz, H-9b), 4.05 (dd, 1H, J4,5 = 2.0 Hz, J5,6 = 4.7 Hz, H-
5), 4.21 (d, 1H, J7,8 = 7.4 Hz, H-7), 4.29 (q, 2H, J = 7.1 Hz,
OCH2CH3), 4.59 (d, 1H, J5,6 = 1.9 Hz, H-6). 13C NMR
(D2O, 150 MHz) δ: 10.2 (CH2CH3), 13.1 (OCH2CH3), 21.7
(COCH3), 23.5 (CH2CH3), 32.3 (C-4), 34.3 (C-3), 47.9 (C-
5), 61.9 (C-9), 63.5 (OCH2CH3), 71.3 (C-8), 77.9 (C-7),
79.9 (C-6), 105.0 (C-2), 168.2 (C-1), 173.9 (COCH3). HR–
MS (ESI) for C15H25NO7: (MNa+) calcd: 354.1528; found:
354.1532.
Major anomer
Ethyl 5-acetamido-2,7-anhydro-3,4,5-trideoxy-4-methyl-
D-glycero-D-talo-non-2-ulopyranosonate (15)
[α]20 +16.5 (c 1.95, CHCl3). IR (cm–1): 1648 (amide
D
C=O), 1746 (ester C=O), 3482 (OH). 1H NMR (CDCl3,
500 MHz) δ: 1.25 (t, 3H, J = 7.1 Hz, CH3CH2O), 1.32 (d,
3H, JCH3,4 = 7.3 Hz, 4-CH3), 1.33, 1.34, 1.39, 1.42 (s, 12H,
C(CH3)2 × 2), 1.78 (d, 1H, J3a,3b = 13.1 Hz, H-3a), 2.16 (s,
4-Methyl hemiaminal 13 (228 mg, 0.548 mmol) was con-
verted into the 2,7-anhydro-4-methylsialoside 15 (263 mg)
using the method described earlier for synthesis of the ethyl
analogue 14. The light brown foamy syrup was of adequate
purity to be used directly in the next reaction. An analytical
sample was purified via flash chromatography (20:3:1
EtOAc–methanol–water v/v/v) to afford the product as a tan
3H, COCH3), 2.44–2.53 (m, 1H, H-4), 2.66 (dd, 1H, J3a,3b
13.0 Hz, J3b,4 = 7.6 Hz, H-3b), 3.49 (t, 1H, J6,7 + J7,8
17.2 Hz, H-7), 3.99 (dd, 1H, J8,9a = 4.9 Hz, J9a,9b = 8.7 Hz,
H-9a), 4.03 (s, 1H, H-5), 4.03–4.07 (m, 1H, H-8), 4.12–4.28
(m, 4H, H-6, H-9b, CH3CH2O), 4.91 (s, 1H, OH). 13C NMR
=
=
solid; mp 117–120 °C (dec). [α]20 +48 (c 0.13, H2O). IR
D
(cm–1): 1647 (amide C=O), 1741 (ester C=O), 3333 (OH).
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