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R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
1
N,N%-dicyclohexyl urea remains undissolved. The
filtrate was concentrated. The TLC (2:1 heptane–
EtOAc) of the residue showed four spots. Compounds
2 (Rf 0.11), 3 (Rf 0.40) and 4 (Rf 0.28) were isolated
from the mixture by column chromatography. The
syrupy product 2 (1.32 g, 25%) crystallized from hep-
tane colorless needles: mp 124–124.5 °C, [h]2D9 −12.9°
(c 1.34, CHCl3). The formyl derivative 3 (0.90 g, 16%)
crystallized from 2:1 light petroleum ether–Et2O: mp
142–143 °C (143–144 °C; DSC measurement); [h]D29
−7.7° (c 1.37, CHCl3); 1.1 g (15%) of compound 4 was
isolated [h]2D2 +7.4° (c 1.07, CHCl3). The latter is easily
soluble in light petroleum ether and numerous other
organic solvents like acetone, EtOAc, and CHCl3.
However, 4 did not crystallize. Only a porous-amor-
phous solid (melting range 85–90 °C) was obtained by
concentration of its light petroleum solution under
reduced pressure.
4: H NMR (300.13 MHz, CDCl3, 55 °C): l 7.39–
7.22 (m, 5 H, Ph), 5.30 (dd, 1 H, J3,4:8.2 Hz, H-3),
5.45 (s, 1 H, CHꢀCCl3), 5.14 (dd, 1 H, J5,6:6.7,
J4,5:9.8 Hz, H-5), 4.80 (d, 1 H, JAB:12.0 Hz,
CH2ꢀPh), 4.79 (dd, 1 H, J1,6:5.5 Hz, H-6), 4.71 (d, 1
H, JAB:12.0 Hz, CH2ꢀPh), 4.89 (br, 1 H, H-4), 4.54
(d, 1 H, J:7.5 Hz, NH), 4.41 (d, 1 H, J:7.5 Hz,
NH), 3.79 (dd, 1 H, J2,3:3.5 Hz, H-2), 3.70 (dd, 1 H,
J1,2:2.0 Hz, H-1), 3.67 (m, 1 H, cyclohexyl-CH), 3.48
(m, 1 H, cyclohexyl-CH), 3.44 (s, 3 H, OMe), 3.24 (br,
1 H, cyclohexyl-CH), 2.04–0.99 (m, 30 H, cyclohexyl-
CH2); 13C NMR (75.5 MHz, CDCl3):
l 156.7
(NHC(O)N), 154.4 (NHC(O)O), 137.9 (i-Ph), 128.3
(m-Ph), 127.7 (o-Ph), 127.6 (p-Ph), 107.2 (CHꢀCCl3),
99.7 (CCl3), 80.3 (C-6), 78.8 (C-1), 77.6 (C-2), 76.9
(C-5), 72.1 (CH2ꢀPh), 70.7 (C-3), 58.0 (OMe), 56.3
(C-4), 55.9 (cyclohexyl-CH), 49.9, 49.4 (cyclohexyl-
CH), 33.8, 33.7, 33.3, 33.2, 32.7, 32.1, 26.6, 26.5, 25.6,
25.6, 25.4, 25.0, 25.0, 24.71, 24.66 (cyclohexyl-CH2); IR
(Nujol): 1631 cm−1 (CꢁO, urea moiety), 1722 cm−1
(CꢁO, carbamoyl moiety), 3330, 3381 cm−1 (NH).
Anal. Calcd for C36H52Cl3N3O7 (745.2): C, 58.03; H,
7.03; N, 5.64. Found: C, 57.69; H, 7.03; N, 5.51.
Moreover, N-acetyl-N,N%-dicyclohexyl-urea (Rf 0.20)
was isolated as crystalline byproduct, mp 126–127 °C
(heptane). It was characterized by X-ray, NMR and
MS analyses.
2: 1H NMR (300.13 MHz, CDCl3): l 7.40–7.22 (m, 5
H, Ph), 5.52 (dd, 1 H, J1,6:3.7, J5,6:2.0 Hz, H-6),
5.39 (s, 1 H, CHꢀCCl3), 4.79 (d, 1 H, JAB:12.0 Hz,
CH2ꢀPh), 4.67 (d, 1 H, JNH,CH:8.0 Hz, NH), 4.59 (d,
1 H, JAB:12.0 Hz, CH2ꢀPh), 4.58 (dd overlapped to
CH2, 1 H, H-5), 4.54 (dd, 1 H, J4,5:6.3 Hz, H-4), 4.16
(dd, 1 H, J3,4:6.3 Hz, H-3), 3.93 (ddd, 1 H, J1,2:2.6,
4J1,5:1.0 Hz, H-1), 3.47 (m, 1 H, cyclohexyl-CH), 3.30
(s, 3 H, OMe), 3.22 (dd, 1 H, J2,3:9.8 Hz, H-2), 2.88
(br, 1 H, OH), 2.00–1.05 (m, 10 H, cyclohexyl-CH2);
13C NMR (75.5 MHz, CDCl3): l 153.5 (C(O)NH),
137.7 (i-Ph), 128.3 (m-Ph), 127.9 (o-Ph), 127.6 (p-Ph),
105.9 (CHꢀCCl3), 99.2 (CCl3), 81.7 (C-4), 78.9 (C-2),
77.8 (C-5), 72.4 (C-1), 71.8 (CH2ꢀPh), 68.6 (C-3), 67.0
(C-6), 57.5 (OMe), 50.2 (cyclohexyl-CH), 33.2, 25.3,
24.7 (cyclohexyl-CH2). Anal. Calcd for C23H30Cl3NO7
(538.8): C, 51.27; H, 5.61; N, 2.60. Found: C, 51.32; H,
5.63; N, 2.74.
L
-1-O-Benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-
4,5-O-trichloroethylidene-muco-inositol (2).—A solu-
tion of muco-inositol 3 (300 mg, 0.5 mmol) in dry
MeOH (10 mL) and Et3N (0.5 mL) was refluxed for 15
min and concentrated under reduced pressure yielding
285 mg (100%) of 2; mp 124 °C (heptane).
L
-1-O-Benzyl-2-O-methyl-4,5-O-trichloroethylidene-
muco-inositol (5).—Compound 2 (446 mg, 1.0 mmol)
was dissolved in 2% methanolic NaOMe (20 mL) and
was refluxed for about 16 h (TLC control). Subse-
quently, the reaction mixture was cooled and neutral-
ized with an acidic ion-exchanger resin (Amberlite
IR-120). After evaporation of the solvent under re-
duced pressure and column chromatographic purifica-
tion (Rf 0.13, 1:2 toluene–EtOAc) 300 mg (85%) of
syrupy 5 was isolated. The product is easily soluble in
Et2O and less soluble in light petroleum, however, it did
not crystallize. Concentration of the ethereal solution of
5 under reduced pressure yielded an amorphous solid
(melting range 52–60 °C); [h]2D9 −25.8° (c 0.9, CHCl3).
1H NMR (250.13 MHz, CDCl3): l 7.41–7.26 (m, 5
H, Ph), 5.40 (s, 1 H, CHꢀCCl3), 4.67 (s, 2 H, CH2ꢀPh),
4.59 (m, 2 H, H-4, H-5), 4.32 (ddd, 1 H, J1,6:6.5,
1
3: H NMR (300.13 MHz, CDCl3): l 8.14 (d, 1 H,
J:1.0 Hz, CHꢁO), 7.40–7.24 (m, 5 H, Ph), 5.54–5.45
(m, 2 H, H-3, H-6), 5.46 (s, 1 H, CHꢀCCl3), 4.76 (d, 1
H, JAB:12.0 Hz, CH2ꢀPh), 4.64 (d, 1 H, JAB:12.0
Hz, CH2ꢀPh), 4.65–4.59 (m, 2 H, H-4, H-5), 4.61 (br, 1
4
H, NH), 3.91 (ddd, 1 H, J1,6:4.8, J1,2:2.5, J:1.0
Hz, H-1), 3.48 (m, 1 H, cyclohexyl-CH), 3.42 (dd, 1 H,
J2,3:9.1 Hz, H-2), 3.34 (s, 3 H, OMe), 2.00–1.05 (m,
10 H, cyclohexyl-CH2); 13C NMR (75.5 MHz, CDCl3):
l 160.2 (CHꢁO), 153.6 (C(O)NH), 137.6 (i-Ph), 128.3
(m-Ph), 127.9 (o-Ph), 127.8 (p-Ph), 106.0 (CHꢀCCl3),
98.9 (CCl3), 79.4, 78.4 (C-4, C-5), 76.9 (C-2), 73.7 (C-1),
72.3 (CH2ꢀPh), 70.2 (C-3), 67.3 (C-6), 58.2 (OMe), 50.3
(cyclohexyl-CH), 33.3, 25.4, 24.7 (cyclohexyl-CH2).
Anal. Calcd for C24H30Cl3NO8 (566.9): C, 50.85; H,
5.33; N, 2.47. Found: C, 50.68; H, 5.19; N, 2.47.
4
J5,6:3.2, J:1.0 Hz, H-6), 4.28 (ddd, 1 H, J3,4:3.3,
4J:1.3 Hz, H-3), 3.77 (dd, 1 H, J1,2:2.8 Hz, H-1),
3.48 (dd, 1 H, J2,3:7.0 Hz, H-2), 3.42 (s, 3 H, OMe),
2.53 (br, 2 H, 2OH); 13C NMR (62.9 MHz, CDCl3): l
137.9 (i-Ph), 128.5 (m-Ph), 127.9 (p-Ph), 127.8 (o-Ph),
106.3 (CHꢀCCl3), 99.6 (CCl3), 81.1, 80.9 (C-4, 5), 78.7
(C-2), 75.9 (C-1), 68.2 (C-3), 68.0 (C-6), 72.4 (CH2ꢀPh),
58.2 (OMe). Anal. Calcd for C16H19Cl3O6 (413.6): C,
46.46; H, 4.63. Found: C, 46.55; H, 4.60.