Molecules 2019, 24, 3758
5 of 8
vacuo to give a residue that was dissolved into cyclohexane (20 mL). The solution was washed with
distilled water (3 10 mL), dried (MgSO ) and solvent was removed in vacuo to yield a mixture of
×
8
4
and 11 (680 mg in total, 36%) as a NMR ratio of 1:1 (some impurities were also detected).
Method 3 (from Seqlene with Recrystallization)
A solution of Seqlene (10 mL, ~7.2 g solid) was diluted with water (60 mL) and passed through
+
a column containing Amberlite IR-120 (H ) cation-exchange resin column (~40 mL). The eluent
◦
was stirred at 100 C for 5 h with cadmium carbonate (2.7 g). Then, cadmium chloride (2.9 g) was
added. After filtration by active carbon, the solution was concentrated in vacuo to half of the volume.
Ethanol (~40 mL) was added until the solution became muddy. The solution was left to recrystallize at
rt overnight to obtain a cadmium salt (1.5 g) of lactones that was subjected to the protection conditions
1
as shown above to form a mixture of triacetonide
8
and 11 (2.0 g) as a ratio of 3:10 according to H NMR.
+
+
20
HRMS m/z (ESI + ve): found 383.1673 [M + Na] , C H O Na requires 383.1676; [
α
]D + 18.9
c 1.25, MeOH); νmax (thin film): 1764 (s, C=O); δ (CD OD, 400MHz): 1.22 (3H, s, CH ), 1.28 (3H, s, CH3),
H
17
28
8
(
3
3
1
3
.29 (6H, s, 2 x CH3), 1.35 (3H, s, CH ), 1.36 (3H, s, CH ), 3.69 (3H, s, OCH ), 3.82–3.85 (1H, m, H7),
3
3
3
0
.92–3.94 (1H, m, H5), 4.00 (1H, dd, H4, J4,3 2.1, J4,5 7.5), 4.01–4.04 (2H, m, H6, H7 ), 4.17 (1H, dd, H3,
(CD OD, 100MHz) 24.1 (CH ), 24.8 (CH ), 25.5 (CH ), 25.7
J3,4 = 2.1, J3,2 7.8), 4.53 (1H, d, H2, J2,3 7.8),
δ
C
3
3
3
3
(
1
CH ), 26.2 (CH ), 26.6 (CH ), 51.5 (OCH ), 67.1 (C7), 75.3 (C2), 77.0 (C5), 77.2 (C6), 77.9 (C4), 78.6 (C3),
3 3 3 3
+
09.5 (C(CH ) ), 109.6 (C(CH ) ), 111.5 (C(CH ) ), 171.3 (C1); m/z (ESI + ve): 383 ([M + Na] , 100%).
3 2 3 2 3 2
3
.3. Methyl 2,3:4,5-Di-O-Isopropylidene-d-glycero-d-ido-Heptonate 12
A solution of triacetonide 11 (4.10 g, 11.4 mmol) in acetic acid:water:methanol (15 mL, 2:1:3) was
◦
stirred at 40 C for 5.5 h until TLC (ethyl acetate) showed the formation of one major product (R 0.60).
f
The reaction mixture was concentrate in vacuo to ~2 mL and then stirred with NaHCO (sat. aq, 40 mL).
3
Cyclohexane (3
×
40 mL) was used to extract the unreacted starting material 11 (~2.2 g) on which
40 mL),
the process was repeated. The aqueous layer was then washed with dichloromethane (3
the combined extracts dried (MgSO ), and the solvent removed in vacuo to obtain 12 (1.20 g, 32%) as
×
4
a clear oil. The unreacted 11 from cyclohexane was recycled by the hydrolysis protocol to obtain more
1
2 (2.21 g, 61% based on recovered 12).
HRMS m/z (ESI + ve): found 343.1360 [M + Na] , C H O Na requires 343.1363; [
+
+
]D20 + 63
α
14
24
8
(c 0.46, MeOH); νmax (thin film): 3469 (br, OH), 1760 (s, C=O);
δ
H
(CDCl , 400MHz) 1.44 (3H, s, CH ),
3
3
1
.45 (3H, s, CH ), 1.47 (3H, s, CH ), 1.51 (3H, s, CH ), 2.42 (1H, t, OH7, J
= JOH,H7
0
5.5), 2.98 (1H, d,
3
3
3
OH,H7
0
OH6, JOH, H6 5.3), 3.72–3.79 (2H, m, H6, H7), 3.83 (3H, s, OCH ), 3.84–3.87 (1H, m, H7 ), 4.12 (1H, t,
3
H5, J5,6 = J5,4 7.3), 4.26 (1H, dd, H4, J4,3 3.1, J4,5 7.3), 4.33 (1H, dd, H3, J3,4 3.1, J3,2 7.6), 4.70 (1H, d, H2,
J2,3 7.6);
δ (CDCl , 100MHz) 26.0 (CH ), 26.6 (CH ), 26.7 (CH ), 27.4 (CH ), 52.6 (OCH ), 63.9 (C7),
C 3 3 3 3 3 3
7
4.7 (C4), 73.0 (C6), 75.5 (C2), 76.8 (C5), 78.4, 78.6 (C3 and C4), 110.0 (C(CH ) ), 111.6 (C(CH ) ), 171.4
3 2 3 2
+
(C1); m/z (ESI + ve): 343 ([M + Na] , 100%).
3
.4. 2,3:4,5-Di-O-Isopropylidene-d-glycero-d-ido-Heptitol 13
Sodium borohydride (334 mg, 8.80 mmol) was added into a solution of 12 (1.41 g, 4.40 mmol)
◦
in methanol (20 mL) at 0 C, and the solution was stirred for 3 h at rt until TLC (ethyl acetate)
showed the consumption of starting material (R 0.57) and the formation of a new product (R 0.37).
f
f
Acetic acid (~0.5 mL) was added into the solution to adjust the pH to 7, and the solvent was removed
in vacuo to obtain a crude product which was further purified by flash column chromatography (ethyl
acetate/methanol, 50:1) to obtain the triol 13 as a white solid (1.20 g, 95%).
+
+
HRMS m/z (ESI + ve): found 315.1415 [M + Na] , C H O Na requires 315.1414;
13
24
7
◦
◦
20
m.p. 92 C–94 C;
[
α
]D + 64 (c, 0.68 in MeOH); νmax (thin film): 3389 (broad, OH);
δ (CD OD,
H 3
4
00MHz) 1.38 (3H, s, CH ), 1.40 (9H, s, 3 x CH ), 3.55 (1H, dd, H7, J 6.3, Jgem 11.0), 3.60–3.53
3
3
7,6
0
(1H, m, H6), 3.65 (1H, dd, H1, J1 5.2, Jgem 11.9), 3.71 (1H, dd, H1 , J
0
4.0, Jgem 11.9), 3.73 (1H, dd,
,2
1 ,2
0
H7 , J7
0
2.9, Jgem 11.0), 3.99 (1H, dd, H3, J3,4 1.5, J3,2 8.5), 4.03–4.05 (2H, m, H4, H5), 4.18 (1H, ddd, H2,
,6