H. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 381–386
385
dropwise at 0 °C. The reaction mixture was stirred and heated at
reflux for 8 h, after which 50 ml of ethyl acetate were added, fol-
lowed by 50 ml of 1 M HCl. The organic layer was separated,
washed with water, and dried over Na2SO4. After evaporation,
the residue was recrystallised from either ethyl acetate or acetone
and the reduction product triol 4 or 5 was obtained as colourless
needles.
(t, J = 9.5 Hz, 1H, Hb-21, 3.10–3.16 (m, 2H, H-24), 3.21–3.41 (m,
10H, H-23, OCH2CH2O), 3.45–3.73 (m, 4H, OCH2CH2O), 4.00–4.22
(m, 4H, OCH2CH2O), 5.36 (s, 1H, H-14), 7.14 (d, J = 8.5 Hz, 2H),
7.21 (t, J = 6.5 Hz, 2H), 7.32 (dd, J = 9.0 Hz, 2H), 7.43 (d, J = 9.0 Hz,
1H), 7.47 (d, J = 10.0 Hz, 1H), 7.85 (t, J = 8.0 Hz, 2H), 7.90 (d,
J = 9.0 Hz, 1H), 7.94 (d, J = 9.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz)
d: 16.1 (C-22), 17.4 (C-2), 17.8 (C-20), 19.5 (C-6), 20.4, 21.1 (C-
18, C-19), 29.5 (C-11), 33.5 (C-17), 35.4 (C-3), 36.0 (C-12), 36.2
(C-7), 37.4 (C-4), 38.1 (C-10), 38.9 (C-1), 40.0 (C-8), 42.4 (C-16),
48.4 (C-5), 50.6 (C-15), 56.0 (C-9), 69.7, 69.7, 69.8, 70.0, 70.3,
70.4, 70.6, 70.8, 71.0, 71.6 (C-23 and C-24), 72.4 (C-21), 115.3,
117.8 (C-60 and C-600), 120.3, 121.5, 123.7, 123.9, 125.2 (C-11),
125.5, 125.6, 126.2, 126.4, 127.9, 128.0, 129.2, 129.4, 129.5,
129.8, 134.1, 134.2, 147.6 (C-14), 154.4, 155.0 (C-50 and C-500); IR
4.4. 15b-Hydroxymethyl-13-(1-methylethyl)-16aH-atis-13-ene-
17,19-diol 4
Yield: 92.2%; mp 172.9–173.6 °C (ref: mp 170 °C15); ½a D25
¼ þ5:2
ꢃ
(c 1.50, CH3OH); 1H NMR (CD3OD, 500 MHz) d: 0.59 (s, 3H, CH3-22),
0.73 (s, 3H, CH3-20), 0.783–0.86 (m, 1H, H -1), 0.99, 1.00 (2d,
a
J = 6.8 Hz, 6H, CH3-18, CH3-19), 1.07–1.17 (m, 1H, H -11), 1.16–
(KBr, m
, cmꢀ1): 3446, 2925, 2868, 1622, 1090; MS (APCI) m/z: 405
a
1.24 (m, 2H, H -3, H-5), 1.31–1.34 (m, 1H, H-9), 1.37–1.52 (m,
(M+H+); MS (APCI) m/z: 804 [M]+. HRMS (ESI) 825.4684
[Mꢀ2H+Na]+, calcd for C53H66O8Na: 825.4701.
a
7H, Hb-1, H-2, Hb-3, H-6, H -7), 1.65 (ddd, J = 13.1, 11.4, 2.6 Hz,
a
1H, Hb-11), 1.83 (dt, J = 9.9, 2.3 Hz, 1H, H-15), 2.02–2.03 (m, 1H,
Hb-7), 2.18–2.22 (m, 2H, H-16, H-17), 2.35 (br s, 1H, H-12), 3.07
Compound 6b: Yield 12.3%; ½a D20
ꢃ
¼ þ65:7 (c 0.1, acetone); 1H
NMR (CDCl3, 500 MHz) d: 0.60 (s, 3H, CH3-22), 0.76 (s, 3H, CH3-
(d, J = 10.9 Hz, 1H, H -21), 3.41 (d, J = 10.6 Hz, 1H, Hb-21), 3.45
20), 0.85–0.90 (m, 1H, H -1), 1.01 (t, J = 6.2 Hz, 6H, CH3-18 and
a
a
(d, J = 10.9 Hz, 1H, H -23), 3.51 (dd, J = 11.4, 3.7 Hz, 1H, H -24)
CH3-19), 1.10–1.13 (m, 2H, H-5 and H -11), 1.22–1.55 (m, 10H,
a
a
a
3.58 (t, J = 10.1 Hz, 1H, Hb-24), 3.76 (dd, J = 11.3, 1.9 Hz, 1H, Hb-
Hb-1, H-2, H -3, H-6, H-7, H-9 and Hb-11), 1.81 (t, J = 10.6 Hz, 1H,
a
23), 5.35 (s, 1H, H-14).
H-15), 1.95 (d, J = 6.8 Hz, 1H, Hb-3), 2.07–2.12 (m, 1H, H-16),
2.20–2.26 (m, 1H, H-17), 2.60 (s, 1H, H-12), 2.91 (t, J = 10.0 Hz,
4.5. 13-(1-Methylethyl)-15b-hydroxymathyl-atis-13-ene-17,18-
1H, H -21), 3.05 (t, J = 9.5 Hz, 1H, Hb-21), 3.12–3.66 (m, 16H, H-
a
diol 5
24, H-23, OCH2CH2O), 3.97–4.16 (m, 4H, OCH2CH2O), 5.34 (s, 1H,
H-14), 7.10, 7.12 (d, J = 8.9 Hz, 2H), 7.19–7.22 (d, J = 8.1 Hz, 2H),
7.29–7.32 (m, 2H), 7.41 (d, J = 9.0 Hz, 1H), 7.46 (d, J = 9.0 Hz, 1H),
7.84, 7.85 (d, J = 8.0 Hz, 2H), 7.91, 7.93 (d, J = 8.9 Hz, 2H); 13C
NMR (CDCl3, 125 MHz) d: 16.2 (C-22), 17.5 (C-2), 17.9 (C-20),
19.7 (C-6), 20.4, 21.2 (C-18 and C-19), 29.8 (C-11), 33.6 (C-17),
35.6 (C-3), 36.2 (C-12), 36.3 (C-7), 37.5 (C-4), 38.2 (C-10), 39.0
(C-1), 40.1 (C-8), 42.4 (C-16), 48.6 (C-5), 51.0 (C-15), 56.1 (C-9),
69.7, 69.89, 69.95, 69.98, 70.1, 70.2, 70.3, 70.7, 71.1, 71.8 (C-23
and C-24), 72.6 (C-21), 116.1, 117.0 (C-60 and C-600), 120.9, 121.1,
123.8, 123.84, 125.0 (C-11), 125.6, 125.7, 126.3, 126.4, 127.96,
128.0, 129.4, 129.5, 129.6, 129.8, 134.3, 134.4, 148.0 (C-14),
Yield: 43.5%; mp 203–204 °C (ref.: mp 205 °C15); ½a D25
¼ ꢀ15:2
ꢃ
(c 1.40, CH3OH); 1H NMR (CDCl3, 500 MHz) d: 0.62 (s, 3H, CH3-
22), 0.74 (s, 3H, CH3-20), 0.76–0.83 (m, 1H, H -1), 0.94–0.98 (m,
a
1H, H -11), 1.02 (d, J = 6.75 Hz, 6H, CH3-18 and CH3-19), 1.14 (d,
a
J = 9.75 Hz, 1H, H -15), 1.23–1.61 (m, 14H, Hb-1, H-2, H-3, H-5,
H-6, H -7, H-9, Hb-11, H -12 and H-16), 1.89–1.94 (m, 1H, Hb-7),
2.30–2.35 (m, 1H, H-17), 2.42 (s, 1H, Hb-12), 2.69 (br s, 2H, OH),
2.96 (t, J = 9.95 Hz, 1H, H -23), 3.11 (d, J = 10.85 Hz, 1H, H -21),
a
a
a
a
a
3.39 (d, J = 10.7 Hz, 1H, Hb-21), 3.53 (t, J = 9.7 Hz, 1H, H -24),
a
3.66 (dd, J = 4.25, 9.45 Hz, 1H, Hb-24), 3.75 (dd, J = 3.75, 9.3 Hz,
1H, Hb-23), 5.32 (s, 1H, H-14); 13C NMR (CDCl3, 125 MHz) d 16.0
(C-22), 17.3 (C-20), 17.7 (C-2), 19.2 (C-6), 20.6, 20.7 (C-18 and C-
19), 23.4 (C-11), 32.7 (C-17), 35.3 (C-12), 35.5 (C-3), 35.6 (C-7),
37.3 (C-4), 37.9 (C-10), 38.7 (C-1), 39.9 (C-8), 44.7 (C-16), 48.2
(C-5), 55.5 (C-15), 55.8 (C-9), 64.5 (C-23), 67.2 (C-24), 72.2 (C-
21), 124.3 (C-14), 150.2 (C-13).
154.6, 154.9 (C-50 and C-500); IR (KBr, , cmꢀ1): 3445, 2924, 1621,
m
1086; MS (APCI) m/z: 803 [MꢀH]+.
Compound 7a: Yield 11.7%; ½a D20
ꢃ
¼ ꢀ39:0 (c 0.1, acetone); 1H
NMR (CDCl3, 500 MHz) d: 0.64 (s, 3H, CH3-22), 0.75 (s, 3H, CH3-
20), 0.78–0.84 (m, 1H, H -1),0.89–1.04 (m, 2H, H -11, H-15),
a
a
1.10 (d, J = 6.5 Hz, 6H, CH3-18 and CH3-19), 1.12–1.17 (m, 2H, H-
5 and H-9), 1.22–1.55 (m, 9H, Hb-1, H-2, H-3, H-6, H -7 and H-
a
4.6. General experimental procedure for the preparation of
chiral 22-crown-6 derivatives 6 and 7
16), 1.77 (sept. d, J = 6.5, 1.2 Hz, 1H, Hb-11), 1.85 (d, J = 12.5 Hz,
1H, Hb-7), 2.34–2.40 (m, 1H, H-17), 2.48 (s, 1H, H-12), 2.86 (t,
J = 9.5 Hz, 1H, H -23), 3.11–3.13 (d, J = 10.5 Hz, 2H, H -21 and
a
a
To a suspension of NaH (0.96 g, 24 mmol 60% in paraffin oil) in
dry THF (80 mL) was slowly added dropwise within 2 h at 45 °C a
mixture of triol 4 or 5 (1.18 g, 3 mmol) and (S)- or (R)-1 (2.4 g,
3 mmol) in dry THF (90 mL). The suspension was stirred for an-
other 72 h at reflux. After cooling to room temperature, 10 mL of
water was added to the mixture in order to deactivate the excess
NaH and the mixture was filtered and concentrated in vacuo.
Water (30 mL) was added to the residue, and then extracted with
dichloromethane (30 mL ꢁ 3). The combined organic layer was
dried over MgSO4 and the dichloromethane was evaporated off.
The residue was purified by chromatography over silica (petroleum
ether/acetone = 9:1) to give 6a, 6b, 7a or 7b as colourless powder.
OCH2CH2O), 3.21–4.22 (m, 19H, Hb-20, H-16, Hb-21, Hb-23, OCH2-
CH2O), 5.31 (s, 1H, H-14), 7.12 (dd, J = 8.5, 4.0 Hz, 2H), 7.20 (m,
2H), 7.32 (dd, J = 7.0 Hz, 2H), 7.45 (t, J = 9.5 Hz, 2H), 7.85 (t,
J = 8.5 Hz, 2H), 7.88 (d, J = 9.0 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H); 13C
NMR (CDCl3, 125 MHz) d: 16.2 (C-22), 17.5 (C-2), 17.9 (C-20),
19.4 (C-6), 20.9 (C-18), 21.0 (C-19), 22.7 (C-11), 33.0 (C-17), 33.8
(C-12), 35.6 (C-3), 35.8 (C-7), 37.4 (C-4), 38.1 (C-10), 38.9 (C-1),
39.9 (C-8), 41.6 (C-16), 48.5 (C-5), 51.0 (C-15), 56.0 (C-9), 69.7,
69.8, 70.0, 70.5, 70.9, 71.0, 71.1, 71.2, 72.5 (C-21), 74.2 (C-24),
74.7 (C-23), 115.4, 117.8 (C-60 and C-600), 120.4, 121.5, 123.7,
123.9, 124.4 (C-14), 125.6, 125.7, 126.3, 126.4, 127. 9, 128.0,
129.3, 129.4, 129.5, 129.7, 134.2, 134.3, 150.2 (C-13), 154.5,
Compound 6a: Yield 11.8%; ½a D20
ꢃ
¼ ꢀ93:3 (c 0.1, acetone); 1H
155.2 (C-50 and C-500); IR (KBr, , cmꢀ1): 3446, 2927, 2862, 1622,
m
NMR (CDCl3, 500 MHz) d: 0.61 (s, 3H, CH3-22), 0.75 (s, 3H, CH3-
1090; MS (APCI) m/z: 804 [M]+; HRMS (ESI) m/z 825.4686
[Mꢀ2H+Na]+, calcd for C53H66O8Na: 825.4701.
20), 0.79–0.89 (m, 1H, H -1), 1.02, 1.04 (2d, J = 7.0 Hz, 6H, CH3-
a
18 and CH3-19), 1.09–1.14 (m, 2H, H-5 and H -11), 1.24–1.61 (m,
Compound 7b: Yield 11.5%; ½a D20
ꢃ
¼ ꢀ35:6 (c 0.1, acetone); 1H
a
10H, Hb-1, H-2, H-3, H-6, H -7, H-9 and Hb-11), 1.75 (t, J = 8.5 Hz,
NMR (CDCl3, 500 MHz) d: 0.64 (s, 3H, CH3-22), 0.76 (s, 3H, CH3-
a
1H, H-15), 1.97 (d, 1H, J = 11 Hz, Hb-7), 2.11–2.23 (m, 2H, H-16
20), 0.79–0.98 (m, 3H, H -1, H-11 and H-15), 1.04, 1.05 (2d,
a
and H-17), 2.65 (s, 1H, H-12), 2.88 (t, J = 9.5 Hz, 1H, H -21), 2.98
J = 7.0 Hz, 6H, CH3-18 and CH3-19), 1.09–1.18 (m, 2H, H -5 and
a
a