R. S. Ward, D. D. Hughes / Tetrahedron 57 (2001) 2057±2064
2061
as a white foam (0.089 g, 57%), mp 119±1218C (Lit.7 123±
1248C); Rf [EtOAc] 0.18; IR (®lm): 3400 cm21 (OH); dH
(400 MHz CDCl3) 6.68 (2H, d, J8.1 Hz, H-50,500), 6.60
(2H, d, J1.7 Hz, H-20,200), 6.58 (2H, m, H-60,600), 3.76
(6H, s, OMe), 3.74 (6H, s, OMe), 3.70 (2H, m, H-1a,4a),
3.44 (2H, dd, J3.9, 11.3 Hz, H-1b,4b), 2.57±2.72 (4H, m,
H-5a,5b,6a,6b), 1.96 (2H, br s, H-2,3),; dC (100.6 MHz,
CDCl3) 148.8 (C-30,300), 147.3 (C-40,400), 133.2 (C-10,100),
121.0 (C-60,600), 112.2 (C-50,500), 111.2 (C-20,200), 60.4 (C-
1,4), 55.9 (2£OMe), 55.8 (2£OMe), 43.9 (C-2,3), 35.8 (C-
5,6); m/z: (e.i.) 391 (21), 390 (M1, 88), 372 (33), 281 (29),
151 (32%); (c.i.) 408 (M1NH41, 100), 390 (18), 170 (71),
156 (57), 151 (43%) [Found: M1 390.2040; C22H30O6
requires: 390.2042].
(28), 156 (27%) [Found: M1 376.1891; C21H28O6 requires:
376.1886].
3.1.4. Preparation of 2-(4-hydroxybenzyl)-3-(3,4-dimeth-
oxybenzyl)-1,4-butanediol (12). The above experimental
procedure was employed using as starting material the
butyrolactone (6).13 Puri®cation via ¯ash chromatography
on silica and elution with CH2Cl2/EtOAc (10:90) afforded
12 as a gum (0.117 g, 65%); Rf [EtOAc] 0.17; IR (®lm):
3281 cm21 (OH); dH (400 MHz CDCl3) 6.91 (2H, d,
J8.4 Hz, H-200,600), 6.70 (1H, d, J8.2 Hz, H-50), 6.65
(2H, d, J8.4 Hz, H-300,500), 6.62 (1H, dd, J1.8, 8.2 Hz,
H-60), 6.56 (1H, d, J1.8 Hz, H-20), 3.79 (3H, s, OMe), 3.75
(3H, s, OMe), 3.72 (2H, m, H-1a,4a), 3.46 (2H, m, H-1b,4b),
2.54±2.72 (4H, m, H-5a,5b,6a,6b), 1.98 (2H, br s, H-2,3);
dC (100.6 MHz, CDCl3) 154.4 (C-400), 148.8 (C-30), 147.2
(C-40), 133.2 (C-10), 132.0 (C-100), 130.0 (C-200,600), 121.1
(C-60), 115.3 (C-300,500), 112.2 (C-50), 111.2 (C-20), 60.4 (C-
1), 60.2 (C-4), 55.9 (OMe), 55.8 (OMe), 44.1 (C-2,3), 35.7
(C-5), 35.2 (C-6); m/z: (e.i.) 346 (M1, 11), 151 (100), 107
(59), 121 (17%); (c.i.) 364 (M1NH41, 100), 346 (52), 326
(21), 154 (16), 124 (19%) [Found: M1 346.1781; C21H28O6
requires: 346.1780].
3.1.2. Preparation of 2-(4-hydroxy-3-methoxybenzyl)-3-
(3,4-dimethoxybenzyl)-1,4-butanediol (10). The above
experimental procedure was employed using as starting
material the butyrolactone (4).13 Puri®cation via ¯ash
chromatography on silica and elution with CH2Cl2/EtOAc
(10:90), followed by crystallisation from EtOAc/hexane,
afforded 10 as a white solid (0.129 g, 62%), mp 115±
1168C (Lit.16 109.5±111.58C); Rf [EtOAc] 0.16; IR (®lm):
3525 (OH), 3400 cm21 (OH); dH (400 MHz CDCl3) 6.72
(1H, d, J8.1 Hz, H-50), 6.68 (1H, d, J7.9 Hz, H-500),
6.60 (1H, dd, J1.7, 8.1 Hz, H-60), 6.56 (1H, m, H-600),
6.56 (1H, m, H-200), 6.53 (1H, d, J1.7 Hz, H-20), 3.77
(2H, m, H-1a,4a), 3.77 (3H, s, OMe), 3.74 (3H, s, OMe),
3.73 (3H, s, OMe), 3.46 (2H, dd, J4.2, 11.3 Hz, H-1b,4b),
2.55±2.72 (4H, m, H-5a,5b,6a,6b), 1.97 (2H, br s, H-2,3);
dC (100.6 MHz, CDCl3) 148.8 (C-30), 147.2 (C-300), 146.5
(C-40), 143.8 (C-400), 133.2 (C-10), 132.4 (C-100), 121.6 (C-
60), 121.0 (C-600), 114.2 (C-50), 112.1 (C-500), 111.4 (C-20),
111.1 (C-200), 60.6 (C-1), 60.4 (C-4), 55.9 (OMe), 55.8
(2£OMe), 43.9 (C-2), 43.8 (C-3), 35.9 (C-5), 35.8 (C-6);
m/z: (e.i.) 377 (21), 376 (M1, 100), 358 (18), 151 (32), 137
(28%); (c.i.) 394 (M1NH41, 100), 376 (33), 170 (24), 156
(23), 151 (21%) [Found: M1 376.1882; C21H28O6 requires:
376.1886].
3.1.5. Preparation of 2,3-bis(4-hydroxy-3-methoxy-
benzyl)-1,4-butanediol (13) (secoisolariciresinol). The
above experimental procedure was employed using as start-
ing material the butyrolactone (7).20 Puri®cation via ¯ash
chromatography on silica and elution with CH2Cl2/EtOAc
(10:90), followed by crystallisation from EtOAc/hexane,
afforded 13 as a white solid (0.129 g, 62%), mp 114±
1158C (Lit.7 113.58C); Rf [EtOAc] 0.15; IR (®lm):
3436 cm21 (OH); dH (400 MHz CDCl3) 6.72 (2H, d, J
8.0 Hz, H-50,500), 6.54 (2H, dd, J1.8, 8.0 Hz, H-60,600),
6.51 (2H, d, J1.8 Hz, H-20,200), 3.72 (6H, s, OMe), 3.75
(2H, m, H-1a,4a), 3.47 (2H, dd, J4.4, 11.4 Hz, H-1b,4b),
2.54±2.69 (4H, m, H-5a,5b,6a,6b), 1.78 (2H, br s, H-2,3);
dC (100.6 MHz, CDCl3) 146.5 (C-30,300), 143.8 (C-40,400),
132.4 (C-10,100), 121.6 (C-60,600), 114.1 (C-50,500), 111.4
(C-20,200), 60.7 (C-1,4), 55.8 (OMe), 55.7 (OMe), 43.8 (C-
3.1.3. Preparation of 2-(3-hydroxy-4-methoxybenzyl)-3-
(3,4-dimethoxybenzyl)-1,4-butanediol (11). The above
experimental procedure was employed using as starting
material the butyrolactone (5).13 Puri®cation via ¯ash
chromatography on silica and elution with CH2Cl2/EtOAc
(10:90), followed by crystallisation from MeOH, afforded
11 as a white foam (0.389 g, 68%), mp 92±948C [Found: C,
67.03; H, 7.50. C21H28O6 requires: C, 67.00; H, 7.50%]; Rf
[EtOAc] 0.15; IR (®lm): 3525 (OH), 3400 cm21 (OH); dH
(400 MHz CDCl3) 6.68 (1H, d, J8.1 Hz, H-500), 6.66 (1H,
d, J8.2 Hz, H-50), 6.66 (1H, d, J2.0 Hz, H-20), 6.62 (1H,
dd, J1.8, 8.1 Hz, H-600), 6.59 (1H, d, J1.8 Hz, H-200),
6.53 (1H, dd, J2.0, 8.2 Hz, H-60), 3.77 (3H, s, OMe),
3.75 (3H, s, OMe), 3.74 (3H, s, OMe), 3.71 (2H, m, H-
1a,4a), 3.43 (2H, dd, J2.9, 11.3 Hz, H-1b,4b), 2.51±2.72
(4H, m, H-5a,5b,6a,6b), 1.97 (2H, br s, H-2,3); dC
(100.6 MHz, CDCl3) 148.8 (C-30), 145.5 (C-300), 147.2 (C-
40), 145.0 (C-400), 133.8 (C-10), 133.2 (C-100), 121.0 (C-60),
120.4 (C-600), 115.3 (C-50), 112.1 (C-500), 111.1 (C-20),
110.8 (C-200), 60.4 (C-1), 60.2 (C-4), 56.0 (OMe), 55.9
(OMe), 55.8 (OMe), 44.1 (C-2,3), 35.7 (C-5), 35.5 (C-6);
m/z: (e.i.) 377 (14), 376 (M1, 50), 224 (83), 188 (90), 177
(100); (c.i.) 394 (M1NH41, 100), 376 (23), 358 (32), 170
2,3), 35.9 (C-5,6); m/z: (e.i.) 363 (16), 362 (M1, 83), 360
1
(59), 344 (30), 177 (83), 137 (35%); (c.i.) 380 (M1NH4
,
100), 362 (29), 360 (27), 156 (36%) [Found: M1 362.1738;
C20H26O6 requires: 362.1729].
3.1.6. Preparation of 2,3-bis(3-hydroxybenzyl)-1,4-
butanediol (14) (enterodiol). The above experimental
procedure was employed using as starting material the
butyrolactone (8).14 Puri®cation via ¯ash chromatography
on silica and elution with EtOAc/hexane (50:50), followed
by crystallisation from EtOAc, and a little CH2Cl2, afforded
14 as a white solid (0.129 g, 62%), mp 165±1678C (Lit.21
171±1738C); Rf [(EtOAc/hexane (50:50)] 0.10; IR (®lm):
3410 (OH), 3400 cm21 (OH); dH (400 MHz CDCl3) 6.48±
6.97 (8H, m, H-20,200,40,400,50,500,60,600), 3.52 (2H, dd, J3.8,
11.2 Hz, H-1a,4a), 3.42 (2H, dd, J5.2, 11.2 Hz, H-1b,4b),
2.53±2.56 (4H, m, H-5a,5b,6a,6b), 1.91 (2H, br s, H-2,3);
dC (100.6 MHz, CDCl3) 157.1 (C-30,300), 142.7 (C-10,100),
129.0 (C-50,500), 120.2 (C-60,600), 115.8 (C-20,200), 112.5
(C-40,400), 60.3 (C-1,4), 43.3 (C-2,3), 35.0 (C-5,6); m/z:
(e.i.) 302 (M1, 11), 284 (13), 121 (100), 105 (41%); (c.i.)
320 (M1NH41, 81), 302 (27), 107 (83), 98 (100%) [Found:
(M1NH4)1 320.1863; C18H22O4 requires: 320.1862].