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S. P. Nikas et al. / Tetrahedron 63 (2007) 8112–8123
J¼1.5 Hz, 1H, 4-H, 24 and d, J¼1.5 Hz, 1H, 4-H, 25, over-
lapping), 6.12 (d, J¼1.5 Hz, 1H, 2-H, 24), 6.10 (d, J¼1.5 Hz,
1H, 2-H, 25), 5.78–5.70 (m, 2H, 8-H, 9-H, 25), 5.66 (dq,
J¼9.5, 3.5 Hz, 1H, 9-H, 24), 4.74 (br s, 2H, OH, 24 and
25), 3.33 (dt, J¼16.5, 2.3 Hz, 1H, 10a-H, 25), 3.25 (br d,
J¼10.8 Hz, 1H, 10a-H, 24), 2.71 (ddd as td, J¼10.6,
4.6 Hz, 1H, 10a-H, 25), 2.44 (t, J¼7.6 Hz, 4H, 10-H, 24
and 25, overlapping), 2.32–2.15 (m, 3H, 8a-H, 8b-H, 24
and 7a-H, 25, overlapping), 1.94–1.84 (m, 4H, 7-H, 24 and
7b-H, 10b-H, 6a-H, 25, overlapping), 1.75 (td, J¼11.2,
1.4 Hz, 1H, 6a-H, 24), 1.56 (qt, J¼7.2 Hz, 4H, 20-H, 24
and 25, overlapping), 1.45–1.39 (m, 4H, 7-H, 6b-Me, 24, es-
pecially 1.41, s, 6b-Me), 1.38 (s, 3H, 6b-Me, 25), 1.35–1.22
(m, 8H, 30-H, 40-H, 24 and 25, overlapping), 1.11 (s, 3H, 6a-
Me, 25), 1.10 (s, 3H, 6a-Me, 24), 0.88 (t, J¼7.1 Hz, 6H, 50-
H, 24 and 25, overlapping). Compound 1h: 1H NMR
(500 MHz, CDCl3) d 8.13 (m as d, J¼1.8 Hz, 1H, 10-H),
6.40 (br s, 1H, OH), 6.25 (d, J¼1.0 Hz, 1H, 4-H), 6.20 (d,
J¼1.0 Hz, 1H, 2-H), 3.39 (br d, J¼11.1 Hz, 1H, 10a-H),
2.60–2.54 (m, 1H, 8-H), 2.50–2.39 (m, 3H, 8-H and 10-H,
overlapping), 2.06–1.99 (m, 1H, 7-H), 1.74 (t, J¼11.7 Hz,
1H, 6a-H), 1.56 (qt, J¼7.6 Hz, 2H, 20-H), 1.48–1.37 (m,
4H, 7-H, 6b-Me, especially 1.44, s, 6b-Me), 1.35–1.23 (m,
4H, 30-H, 40-H), 1.12 (s, 3H, 6a-Me), 0.88 (t, J¼6.9 Hz,
3H, 50-H). Mass spectrum m/z (relative intensity) 344 (M+,
100), 329 (78), 299 (92), 288 (54). Exact mass calculated
for C21H28O4, 344.1988; found, 344.1983.
hexane/TMEDA (64 mL, 1:1 ratio) and gave a mixture of
18c and 19c as a pale yellow semisolid material (320 g,
49% yield, eluted by 45% ethyl acetate in hexane, 18c/19c
(85:15) on the basis of 1H NMR analysis). Recrystallization
of this mixture from chloroform gave pure 18c (137 mg,
21% yield from 16c) as a white solid. Mp¼216–218 ꢁC;
1H NMR (500 MHz, CDCl3+CD3COCD3) d 8.11 (br s,
1H, 10-H), 6.60 (br s, 1H, OH), 6.25 (d, J¼1.0 Hz, 1H, 4-
H), 6.21 (d, J¼1.0 Hz, 1H, 2-H), 3.39 (br d, J¼11.0 Hz,
1H, 10a-H), 2.62–2.52 (m, 1H, 8-H), 2.50–2.38 (m, 3H, 8-
H and 10-H, overlapping), 2.06–1.98 (m, 1H, 7-H), 1.74 (t,
J¼11.5 Hz, 1H, 6a-H), 1.56 (qt, J¼7.5 Hz, 2H, 20-H),
1.48–1.37 (m, 4H, 7-H, 6b-Me, especially 1.44, s, 6b-Me),
1.34–1.20 (m, 4H, 30-H, 40-H), 1.12 (s, 3H, 6a-Me). Mass
spectrum m/z (relative intensity) 347 (M+, 100), 332 (71),
302 (95), 288 (25), 279 (21), 220 (14), 196 (17), 174 (11).
Exact mass calculated for C21H25D3O4, 347.2179; found,
347.2176. The deuterium incorporation on the molecular
ion cluster using FI was 2H3: 96.4%, 2H2: 2.2%, 2H1:
1.0%, and 2H0: 0.4%.
4.22. (6aR,10aR)-6a,7,8,10a-Tetrahydro-1-hydroxy-6,6-
dimethyl-3-(20,20,30,30,30-2H5-propyl)-6H-dibenzo[b,d]-
pyran-9-carboxylic acid (18d)
The synthesis was carried out as described for 1h starting
from 17d (2.1 g, 3.66 mmol) and n-BuLi (6.73 mL,
16.83 mmol, using a 2.5 M solution in hexane) in dry hex-
ane/TMEDA (122 mL, 1:1) and gave a mixture of 18d and
19d as a pale yellow semisolid material [600 mg, 51% yield,
eluted by 45% ethyl acetate in hexane, 18d/19d (87:13) on
the basis of 1H NMR analysis]. Recrystallization of this mix-
ture from chloroform/hexane gave pure 18d (270 mg, 23%
yield from 16d) as a white solid. Mp¼161–163 ꢁC; 1H
NMR (500 MHz, CDCl3+CD3COCD3) d 8.14 (m as d,
J¼2.0 Hz, 1H, 10-H), 6.62 (br s, 1H, OH), 6.24 (d,
J¼1.5 Hz, 1H, 4-H), 6.21 (d, J¼1.5 Hz, 1H, 2-H), 3.39 (br
d, J¼11.5 Hz, 1H, 10a-H), 2.61–2.52 (m, 1H, 8-H), 2.48–
2.36 (m, 3H, 8-H, 10-H especially 2.40, s, 10-H), 2.06–1.98
(m, 1H, 7-H), 1.74 (td, J¼12.0, 2.0 Hz, 1H, 6a-H), 1.47–
1.37 (m, 4H, 7-H, 6b-Me, especially 1.42, s, 6b-Me), 1.12
(s, 3H, 6a-Me). Mass spectrum m/z (relative intensity) 321
(M+, 100), 306 (74), 276 (98), 260 (26), 208 (27), 170
(27), 115 (11), 69 (13). Exact mass calculated for
C19H19D5O4, 321.1985; found, 321.1988. The deuterium in-
4.20. (6aR,10aR)-6a,7,8,10a-Tetrahydro-1-hydroxy-6,6-
dimethyl-3-(40,40,50,50,50-2H5-pentyl)-6H-dibenzo[b,d]-
pyran-9-carboxylic acid (18b)
The synthesis was carried out as described for 1h starting
from 17b (1.730 g, 2.88 mmol) and n-BuLi (5.3 mL,
13.24 mmol, using a 2.5 M solution in hexane) in dry hex-
ane/TMEDA (96 mL, 1:1 ratio) and gave a mixture of 18b
and 19b as a pale yellow semisolid material [510 mg, 51%
yield, eluted by 45% ethyl acetate in hexane, ratio of 18b/
19b (87:13) on the basis of 1H NMR analysis]. Recrystalli-
zation of this mixture from chloroform gave pure 18b
(235 mg, 23% yield from 16b) as a white solid. Mp¼215–
1
217 ꢁC; H NMR (500 MHz, CDCl3+CD3COCD3) d 8.11
(m as d, J¼1.8 Hz, 1H, 10-H), 6.26 (d, J¼1.0 Hz, 1H, 4-H),
6.19 (d, J¼1.0 Hz, 1H, 2-H), 6.08 (br s, 1H, OH), 3.39 (br d,
J¼11.2 Hz, 1H, 10a-H), 2.60–2.54 (m, 1H, 8-H), 2.50–2.39
(m, 3H, 8-H and 10-H, overlapping), 2.06–1.99 (m, 1H, 7-
H), 1.74 (t, J¼11.8 Hz, 1H, 6a-H), 1.55 (qt, J¼7.7 Hz, 2H,
20-H), 1.47–1.37 (m, 4H, 7-H, 6b-Me, especially 1.44, s, 6b-
Me), 1.27 (t, J¼7.6 Hz, 2H, 30-H), 1.12 (s, 3H, 6a-Me).
Mass spectrum m/z (relative intensity) 349 (M+, 82), 334
(56), 304 (81), 288 (31), 260 (21), 236 (16), 223 (45), 205
(100), 168 (47), 141 (49), 115 (56), 91 (39), 77 (91). Exact
mass calculated for C21H23D5O4, 349.2301; found,
349.2300. The deuterium incorporation on the molecular ion
cluster using FI was 2H5: 97.1%, 2H4: 2.2%, and 2H3: 0.7%.
2
corporation on the molecular ion cluster using FI was H5:
96.8%, 2H4: 1.9%, 2H3: 0.7%, and 2H1: 0.6%.
4.23. (6aR,10aR)-6a,7,8,10a-Tetrahydro-1-hydroxy-6,6-
dimethyl-3-(30,30,30-2H3-propyl)-6H-dibenzo[b,d]pyran-
9-carboxylic acid (18e)
The synthesis was carried out as described for 1h starting
from 17e (1.668 g, 2.92 mmol) and n-BuLi (5.38 mL,
13.44 mmol, using a 2.5 M solution in hexane) in dry hex-
ane/TMEDA (97 mL, 1:1 ratio) and gave a mixture of 18e
and 19e as a pale yellow semisolid material [468 mg, 50%
yield, eluted by 45% ethyl acetate in hexane, 18e/19e
(86:14) on the basis of 1H NMR analysis]. Recrystallization
of this mixture from chloroform/hexane gave pure 18e
(209 mg, 22% yield from 16e) as a white solid. Mp¼161–
4.21. (6aR,10aR)-6a,7,8,10a-Tetrahydro-1-hydroxy-6,6-
dimethyl-3-(50,50,50-2H3-pentyl)-6H-dibenzo[b,d]pyran-
9-carboxylic acid (18c)
The synthesis was carried out as described for 1h starting
from 17c (1.127 g, 1.88 mmol) and n-BuLi (3.46 mL,
8.64 mmol, using a 2.5 M solution in hexane) in dry
1
163 ꢁC; H NMR (500 MHz, CDCl3+CD3COCD3) d 8.13
(m as d, J¼1.7 Hz, 1H, 10-H), 6.42 (br s, 1H, OH), 6.25