Research Article
MedChemComm
containing Et3N (0.90 mL), kept at 23 °C for 12 h. Then the
mixture was treated with acidic resin (Dowex 50WX8, H+)
until acidic pH and the resin was filtered and washed with
MeOH (2 mL × 3). Finally, the solvent was removed under
reduced pressure and the residue was recovered with
aqueous methanol and lyophilized, to afford, after
preparative HPLC, the desired free glycal 7b.
Preparation of 2,6-anhydro-5-(2,2,3,3,3-pentafluoropropionamido)-
3,5-dideoxy-D-glycero-D-galacto-non-2-enoic acid (2c). Starting
from protected glycal 8c12c (80 mg, 0.14 mmol), according to
the general two step procedure Zemplén reaction followed by
selective hydrolytic method A, glycal 2c was obtained (48 mg,
86%), as a white solid, showing: [α]2D3, +26.7 (c 1 in MeOH);
δH (CD3OD) 5.96 (1H, d, J3,4 2.2 Hz, 3-H), 4.50 (1H, dd, J4,3
2.2, J4,5 9.0 Hz, 4-H), 4.41 (1H, d app, J6,5 11.0 Hz, 6-H), 4.24
(1H, dd, J5,4 9.0, J5,6 11.0 Hz, 5-H), 3.86 (1H, ddd, J8,9a 2.9,
J8,9b 5.6, J8,7 9.2 Hz, 8-H), 3.80 (1H, dd, J9a,8 2.9, J9a,9b 11.4 Hz,
9a-H), 3.62 (1H, dd, J9b,8 5.6, J9b,9a 11.4 Hz, 9b-H), 3.51 (1H, d
app, J7,8 9.2 Hz, 7-H); δC (CD3OD) 165.6 (C-1), 160.0 (t, JC,F 26
Hz, COCF2), 145.3 (C-2), 125.0–110.0 (2C, CF2CF3), 113.6
(C-3), 77.2 (C-6), 71.5 (C-8), 70.1 (C-7), 68.0 (C-4), 65.0 (C-9),
52.2 (C-5); HRMS (ESI-TOF, m/z): calcd for C12H13F5NO8
[M − H]− 394.0567, found 394.0559.
Preparation of 2,6-anhydro-5-(2,2,3,3,4,4,4-heptafluorobutanamido)-
3,5-dideoxy-D-glycero-D-galacto-non-2-enoic acid (2d). Starting
from protected glycal 8d12c (88 mg, 0.14 mmol), according to
the general two step procedure Zemplén reaction followed by
selective hydrolytic method A, glycal 2d was obtained (52 mg,
84%), as a white solid, showing: [α]2D3, +19.9 (c 1 in MeOH);
δH (CD3OD) 5.96 (1H, d, J3,4 2.3 Hz, 3-H), 4.50 (1H, dd, J4,3
2.3, J4,5 8.9 Hz, 4-H), 4.41 (1H, dd, J6,7 < 1.0, J6,5 11.0 Hz,
6-H), 4.24 (1H, dd, J5,4 8.9, J5,6 11.0 Hz, 5-H), 3.89 (1H, ddd,
J8,9a 2.8, J8,9b 5.6, J8,7 9.2 Hz, 8-H), 3.82 (1H, dd, J9a,8 2.8, J9a,9b
11.4 Hz, 9a-H), 3.56 (1H, dd, J9b,8 5.6, J9b,9a 11.4 Hz, 9b-H),
3.52 (1H, dd, J6,7 < 1.0, J7,8 9.2 Hz, 7-H); δC (CD3OD) 165.6
(C-1), 159.8 (t, JC–F 26 Hz, COCF2), 145.3 (C-2), 122.0–110.0
(3C, CF2CF2CF3), 113.6 (C-3), 77.2 (C-6), 71.5 (C-8), 70.2 (C-7),
67.9 (C-4), 65.0 (C-9), 52.3 (C-5); HRMS (ESI-TOF, m/z): calcd
for C13H13F7NO8 [M − H]− 444.0535, found 444.0551.
Preparation of 2,6-anhydro-5-acetamido-3,5-dideoxy-D-glycero-
D-talo-non-2-enoic acid (7a). Starting from protected glycal
9a13,14 (66 mg, 0.14 mmol), according to the general two step
procedure Zemplén reaction followed by selective hydrolytic
method A, glycal 7a was obtained (31 mg, 75%), as a white
solid, showing: [α]2D3, −98.9 (c 1 in MeOH); δH (CD3OD) 6.02
(1H, d, J3,4 5.0 Hz, 3-H), 4.27–4.14 (3H, overlapping, 4-H, 6-H
and 5-H), 3.92 (1H, ddd, J8,9a 2.3, J8,9b 5.3, J8,7 9.2 Hz, 8-H),
3.83 (1H, dd, J9a,8 2.3, J9a,9b 11.4 Hz, 9a-H), 3.67 (1H, dd, J9b,8
5.3, J9b,9a 11.4 Hz, 9b-H), 3.58 (1H, d app, J7,8 9.2 Hz, 7-H),
2.05 (1H, s, NHCOCH3); δC (CD3OD) 174.2 (C-1), 167.5
(NHCOCH3), 148.2 (C-2), 108.6 (C-3), 73.3 (C-6), 71.5 (C-8),
70.1 (C-7), 65.0 (C-9), 62.1 (C-5), 49.4 (C-4), 22.8 (NHCOCH3);
HRMS (ESI-TOF, m/z): calcd for C11H16NO8 [M − H]− 290.0881,
found 290.0855.
protected glycal 9b13,14 (74 mg, 0.14 mmol), according to the
general two step procedure Zemplén reaction followed by
selective hydrolytic method B, glycal 7b was obtained (42 mg,
87%), as a white solid, showing: m.p. 112–114 °C (from
MeOH–diisopropylether); [α]2D3, −98.8 (c 1 in MeOH); δH
(CD3OD) 6.14 (1H, d, J3,4 5.6 Hz, 3-H), 4.45 (1H, d app, J6,5
11.3 Hz, 6-H), 4.32 (1H, dd, J5,4 3.4, J5,6 11.3 Hz, 5-H),
4.28–4.23 (1H, m, 4-H), 4.00 (1H, ddd, J8,9a 2.1, J8,9b 5.4, J8,7
9.2 Hz, 8-H), 3.84 (1H, dd, J9a,8 2.1, J9a,9b 11.4 Hz, 9a-H),
3.67 (1H, dd, J9b,8 5.4, J9b,9a 11.4 Hz, 9b-H), 3.67 (1H, d
app, J7,8 9.2 Hz, 7-H); δC (CD3OD) 165.8 (C-1), 158.9 (1C, q,
JC,F 37 Hz, COCF3), 146.4 (C-2), 121.0–114.0 (1C, q, JC,F 287
Hz, CF3), 110.4 (C-3), 72.9 (C-6), 71.8 (C-8), 69.9 (C-7), 64.9
(C-9), 61.3 (C-5), 50.1 (C-4); HRMS (ESI-TOF, m/z): calcd for
C11H13F3NO8 [M − H]− 344.0599, found 344.0583.
Preparation of 2,6-anhydro-5-(2,2,3,3,3-pentafluoropropionamido)-
3,5-dideoxy-D-glycero-D-talo-non-2-enoic acid (7c). Starting from
protected glycal 9c13,14 (81 mg, 0.14 mmol), according to the
general two step procedure Zemplén reaction followed by
selective hydrolytic method A, glycal 7c was obtained (40 mg,
72%), as a white solid, showing: m.p. 107–109 °C (from
MeOH–diisopropylether); [α]2D3, −119.2 (c 1 in MeOH); δH
(CD3OD) 6.14 (1H, d, J3,4 5.7 Hz, 3-H), 4.46 (1H, d app, J6,5 11.4
Hz, 6-H), 4.36 (1H, dd, J5,4 3.6, J5,6 11.4 Hz, 5-H), 4.27–4.23 (1H,
m, 4-H), 3.91 (1H, ddd, J8,9a 2.7, J8,9b 5.6, J8,7 9.2 Hz, 8-H), 3.84
(1H, dd, J9a,8 2.7, J9a,9b 11.4 Hz, 9a-H), 3.65 (1H, dd, J9b,8 5.6,
J9b,9a 11.4 Hz, 9b-H), 3.57 (1H, d app, J7,8 9.2 Hz, 7-H); δC (CD3-
OD) 165.8 (C-1), 159.4 (1C, t, JC,F 26 Hz, COCF2), 146.4 (C-2),
123.0–106.0 (2C, CF2CF3), 110.5 (C-3), 72.9 (C-6), 71.8 (C-8),
70.0 (C-7), 65.0 (C-9), 61.3 (C-5), 50.1 (C-4); HRMS (ESI-TOF, m/
z): calcd for C12H13F5NO8 [M − H]− 394.0567, found 394.0560.
Preparation of 2,6-anhydro-5-(2,2,3,3,4,4,4-heptafluorobutanamido)-
3,5-dideoxy-D-glycero-D-talo-non-2-enoic acid (7d). Starting from
protected glycal 9d (88 mg, 0.14 mmol), according to the general
two step procedure Zemplén reaction followed by selective
hydrolytic method A, glycal 7d was obtained (44 mg, 71%), as a
white solid, showing: [α]2D3, −103.6 (c 1 in MeOH); δH (CD3OD)
6.13 (1H, d, J3,4 5.6 Hz, 3-H), 4.47 (1H, d app, J6,5 11.3 Hz, 6-H),
4.36 (1H, dd, J5,4 3.2, J5,6 11.3 Hz, 5-H), 4.24 (1H, dd, J4,5 3.2, J4,3
5.6 Hz, 4-H), 3.91 (1H, ddd, J8,9a 2.1, J8,9b 5.6, J8,7 9.1 Hz, 8-H),
3.85 (1H, dd, J9a,8 2.1, J9a,9b 11.4 Hz, 9a-H), 3.65 (1H, dd, J9b,8
5.6, J9b,9a 11.4 Hz, 9b-H), 3.58 (1H, d app, J7,8 9.1 Hz, 7-H); δC
(CD3OD) 166.0 (C-1), 159.2 (1C, t, JC,F 26 Hz, COCF2), 146.5 (C-
2), 121.0–106.0 (3C, CF2CF2CF3), 110.3 (C-3), 72.9 (C-6), 71.9 (C-
8), 70.1 (C-7), 65.0 (C-9), 61.3 (C-5), 50.2 (C-4); HRMS (ESI-TOF,
m/z): calcd for C13H13F7NO8 [M − H]− 444.0535, found 444.0535.
Synthesis of N-unfluoracyl glycals 2e–f
General procedure. The peracetylated glycal 8b12c (260 mg,
0.5 mmol) were treated with a methanolic solution of
NaOMe, freshly prepared by dissolving sodium metal (0.22
mmol, 5 mg) in anhydrous MeOH (2 mL). The reaction mix-
ture was stirred at 23 °C for 1 h, and then quenched with
acidic resin (Dowex 50WX8, H+). The resin was filtered off
and washed with MeOH (2 mL) and the combined filtrates
Preparation of 2,6-anhydro-5-(2,2,2-trifluoroacetamido)-3,5-
dideoxy-D-glycero-D-talo-non-2-enoic acid (7b). Starting from
Med. Chem. Commun.
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