M
G. Varró et al.
Paper
Synthesis
Anal. Calcd for C24H29NO9: C, 60.62; H, 6.15; N, 2.95. Found: C, 60.61;
H, 6.16; N, 2.94.
combined organic layer was washed with brine, dried over Na2SO4
and concentrated in vacuo to afford diacetate (–)-25a, (–)-25b or (–)-
25c.
(+)-5-(3,4-Diethoxy-5-methoxyphenyl)-2,3-dihydroxy-4-(meth-
oxycarbonylamino)cyclohexyl Benzoate [(+)-24b]
Yield: 0.64 g (99%); white solid (fluffy); mp 76–83 °C; [α]D22 +66.1 (c
(–)-2,3-Diacetoxy-4-(methoxycarbonylamino)-5-(3,4,5-trimeth-
oxyphenyl)cyclohexyl Benzoate [(–)-25a]
Yield: 0.72 g (99%); white solid (fluffy); mp 81–89 °C; [α]D22 –12.9 (c
1, CHCl3); Rf = 0.46 (CH2Cl2–MeOH, 10:1).
1, CHCl3); Rf = 0.76 (CH2Cl2–MeOH, 10:1).
IR (KBr): 3481, 3411, 3302, 2978, 1708, 1587, 1556, 1508, 1456, 1363,
1274, 1118, 1074, 719 cm–1
.
IR (KBr): 3380, 2945, 2842, 1751, 1725, 1592, 1538, 1510, 1457, 1369,
1274, 1244, 1127, 1054, 715 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 8.06 (d, J = 7.2 Hz, 2 H, 2-HBz and 6-
H
H
Bz), 7.61 (t, J = 7.2 Hz, 1 H, 4-HBz), 7.49 (t, J = 7.5 Hz, 2 H, 3-HBz and 5-
Bz), 6.40 (s, 2 H, 2-HAr and 6-HAr), 5.44 (q, J = 3.0 Hz, 1 H, 1-H), 4.62
1H NMR (300 MHz, CDCl3): δ = 8.10 (d, J = 7.5 Hz, 2 H, 2-HBz and 6-
H
H
Bz), 7.63 (t, J = 7.5 Hz, 1 H, 4-HBz), 7.51 (t, J = 7.5 Hz, 2 H, 3-HBz and 5-
Bz), 6.44 (s, 2 H, 2-HAr and 6-HAr), 5.50 (t, J = 3.0 Hz, 1 H, 1-H/2-H),
(d, J = 6.3 Hz, 1 H, NH), 4.44 (br s, 1 H, OH), 4.22–4.19 (m, 1 H, 2-H),
4.05 (q, J = 6.9 Hz, 2 H, OCH2CH3), 4.04 (q, J = 6.9 Hz, 2 H, OCH2CH3),
4.02–3.99 (m, 1 H, 4-H), 3.98–3.95 (m, 1 H, 3-H), 3.82 (s, 3 H, OCH3),
3.56 (s, 3 H, NHCOOCH3), 3.32 (br s, 1 H, OH), 2.83 (ddd, J = 12.9, 10.8,
3.0 Hz, 1 H, 5-H), 2.33 (ddd, J = 14.7, 12.9, 2.4 Hz, 1 H, 6-Hβ), 2.07 (dt,
J = 14.7, 2.7 Hz, 1 H, 6-Hα), 1.41 (t, J = 6.9 Hz, 3 H, OCH2CH3), 1.34 (t,
J = 6.9 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 165.1 (Ph–CO), 158.9 (NHCOOCH3),
153.9 (3-CAr), 153.1 (5-CAr), 136.6 (1-CAr), 135.8 (4-CAr), 133.3 (4-CBz),
130.0 (1-CBz), 129.7 (2-CBz and 6-CBz), 128.6 (3-CBz and 5-CBz), 106.1
(2-CAr), 104.6 (6-CAr), 74.0 (3-C), 71.3 (1-C), 70.2 (2-C), 68.8
(OCH2CH3), 64.7 (OCH2CH3), 56.3 (OCH3), 55.6 (4-C), 52.6
(NHCOOCH3), 43.0 (5-C), 32.8 (6-C), 15.5 (OCH2CH3), 14.9 (OCH2CH3).
5.38 (dd, J = 10.5, 3.0 Hz, 1 H, 3-H), 5.31–5.28 (m, 1 H, 1-H/2-H), 4.46
(d, J = 9.5 Hz, 1 H, NH), 4.34–4.30 (m, 1 H, 4-H), 3.85 (s, 6 H, 2 × OCH3),
3.82 (s, 3 H, OCH3), 3.51 (s, 3 H, NHCOOCH3), 3.00 (td, J = 11.0, 3.0 Hz,
1 H, 5-H), 2.25 (s, 3 H, CH3CO), 2.21–2.16 (m, 2 H, 6-Hα and 6-Hβ), 2.03
(s, 3 H, CH3CO).
13C NMR (75 MHz, CDCl3): δ = 170.1 (CH3CO), 169.5 (CH3CO), 164.9
(Ph–CO), 156.6 (NHCOOCH3), 153.3 (3-CAr and 5-CAr), 136.6 (1-CAr),
135.9 (4-CAr), 133.6 (4-CBz), 129.9 (2-CBz and 6-CBz), 129.4 (1-CBz),
128.7 (3-CBz and 5-CBz), 104.9 (2-CAr and 6-CAr), 71.4 (3-C), 69.5 (1-C),
69.3 (2-C), 60.8 (OCH3), 56.3 (2 × OCH3), 54.1 (4-C), 52.1 (NHCOOCH3),
43.9 (5-C), 33.0 (6-C), 21.0 (CH3CO), 20.7 (CH3CO).
Anal. Calcd for C28H33NO11: C, 60.10; H, 5.94; N, 2.50. Found: C, 60.09;
H, 5.93; N, 2.50.
Anal. Calcd for C26H33NO9: C, 62.02; H, 6.61; N, 2.78. Found: C, 62.01;
H, 6.61; N, 2.77.
(–)-2,3-Diacetoxy-5-(3,4-diethoxy-5-methoxyphenyl)-4-(meth-
oxycarbonylamino)cyclohexyl Benzoate [(–)-25b]
Yield: 0.76 g (100%); white solid (fluffy); mp 71–78 °C; [α]D22 –13.2 (c
(+)-2,3-Dihydroxy-4-(methoxycarbonylamino)-5-(3,4,5-triethoxy-
phenyl)cyclohexyl Benzoate [(+)-24c]
Yield: 0.39 g (59%); white solid (fluffy); mp 76–80 °C; [α]D22 +62.4 (c
1, CHCl3); Rf = 0.80 (CH2Cl2–MeOH, 10:1).
1, CHCl3); Rf = 0.46 (CH2Cl2–MeOH, 10:1).
IR (KBr): 3376, 2979, 1752, 1726, 1589, 1540, 1508, 1455, 1370, 1273,
IR (KBr): 3483, 3422, 2984, 2929, 2878, 1710, 1587, 1551, 1507, 1440,
1244, 1124, 1053, 715 cm–1
.
1388, 1273, 1232, 1124, 1072, 810, 669 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 8.10 (d, J = 7.2 Hz, 2 H, 2-HBz and 6-
1H NMR (300 MHz, CDCl3): δ = 8.06 (d, J = 7.2 Hz, 2 H, 2-HBz and 6-
H
H
Bz), 7.64 (t, J = 7.5 Hz, 1 H, 4-HBz), 7.52 (t, J = 7.2 Hz, 2 H, 3-HBz and 5-
Bz), 6.43 (s, 2 H, 2-HAr and 6-HAr), 5.51 (t, J = 3.0 Hz, 1 H, 1-H/2-H),
H
H
Bz), 7.62 (t, J = 7.2 Hz, 1 H, 4-HBz), 7.49 (t, J = 7.5 Hz, 2 H, 3-HBz and 5-
Bz), 6.39 (s, 2 H, 2-HAr and 6-HAr), 5.44 (q, J = 3.0 Hz, 1 H, 1-H), 4.60
5.38 (dd, J = 10.5, 3.0 Hz, 1 H, 3-H), 5.32–5.29 (m, 1 H, 1-H/2-H), 4.43
(d, J = 9.9 Hz, 1 H, NH), 4.34–4.31 (m, 1 H, 4-H), 4.06 (q, J = 7.2 Hz, 2 H,
OCH2CH3), 4.04 (q, J = 7.2 Hz, 2 H, OCH2CH3), 3.84 (s, 3 H, OCH3), 3.49
(s, 3 H, NHCOOCH3), 2.97 (td, J = 11.1, 5.1 Hz, 1 H, 5-H), 2.25 (s, 3 H,
CH3CO), 2.21–2.17 (m, 2 H, 6-Hα and 6-Hβ), 2.04 (s, 3 H, CH3CO), 1.42
(t, J = 6.9 Hz, 3 H, OCH2CH3), 1.34 (t, J = 7.2 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 170.7 (CH3CO), 169.4 (CH3CO), 164.9
(Ph–CO), 156.5 (NHCOOCH3), 153.6 (3-CAr), 152.8 (5-CAr), 136.6 (1-
CAr), 135.5 (4-CAr), 133.6 (4-CBz), 129.8 (2-CBz and 6-CBz), 129.4 (1-CBz),
128.6 (3-CBz and 5-CBz), 106.5 (2-CAr), 105.0 (6-CAr), 71.3 (3-C), 69.5
(1-C), 69.3 (2-C), 68.7 (OCH2CH3), 64.8 (OCH2CH3), 56.3 (OCH3), 52.9
(4-C), 52.1 (NHCOOCH3), 43.8 (5-C), 33.9 (6-C), 21.1 (CH3CO), 20.7
(CH3CO), 15.5 (OCH2CH3), 14.9 (OCH2CH3).
(d, J = 6.0 Hz, 1 H, NH), 4.46 (br s, 1 H, OH), 4.22–4.19 (m, 1 H, 2-H),
4.04 (q, J = 6.9 Hz, 6 H, 3 × OCH2CH3), 4.02–3.99 (m, 1 H, 4-H), 3.98–
3.95 (m, 1 H, 3-H), 3.57 (s, 3 H, NHCOOCH3), 3.32 (br s, 1 H, OH), 2.80
(ddd, J = 12.6, 10.5, 3.0 Hz, 1 H, 5-H), 2.32 (ddd, J = 14.7, 12.9, 2.4 Hz, 1
H, 6-Hβ), 2.07 (dt, J = 14.7, 2.7 Hz, 1 H, 6-Hα), 1.40 (t, J = 6.9 Hz, 6 H,
2 × OCH2CH3), 1.34 (t, J = 6.9 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 165.1 (Ph–CO), 158.9 (NHCOOCH3),
153.2 (3-CAr and 5-CAr), 137.2 (1-CAr), 135.7 (4-CAr), 133.3 (4-CBz),
130.0 (1-CBz), 129.7 (2-CBz and 6-CBz), 128.5 (3-CBz and 5-CBz), 106.3
(2-CAr and 6-CAr), 74.1 (3-C), 71.3 (1-C), 70.2 (2-C), 68.8 (OCH2CH3),
64.8 (2 × OCH2CH3), 55.7 (4-C), 52.6 (NHCOOCH3), 42.9 (5-C), 32.8 (6-
C), 15.6 (OCH2CH3), 15.0 (2 × OCH2CH3).
Anal. Calcd for C27H35NO9: C, 62.66; H, 6.82; N, 2.71. Found: C, 62.65;
H, 6.81; N, 2.72.
Anal. Calcd for C30H37NO11: C, 61.32; H, 6.35; N, 2.38. Found: C, 61.33;
H, 6.34; N, 2.37.
(Trialkyloxyphenyl)cyclohexanediyl Diacetates (–)-25a, (–)-25b
and (–)-25c; General Procedure
(–)-2,3-Diacetoxy-4-(methoxycarbonylamino)-5-(3,4,5-triethoxy-
phenyl)cyclohexyl Benzoate [(–)-25c]
Compound (+)-24a, (+)-24b or (+)-24c (1.30 mmol) was dissolved in
acetyl chloride (4.86 mL, 5.37 g, 0.07 mol) and the solution was
stirred at r.t. for 20–24 h. Then, it was poured into a saturated NaHCO3
solution (424 mL) at 0 °C and extracted with EtOAc (4 × 90 mL). The
Yield: 0.78 g (100%); white solid (fluffy); mp 69–74 °C; [α]D22 –10.3 (c
1, CHCl3); Rf = 0.86 (CH2Cl2–MeOH, 10:1).
IR (KBr): 3399, 2974, 2933, 2886, 1751, 1722, 1587, 1524, 1509, 1480,
1444, 1369, 1270, 1250, 1121, 1030, 722 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–S