J. Deguchi et al. / Tetrahedron Letters 55 (2014) 1362–1365
1363
Table 1
166.8. The presence of 5-(2-hydroxypropyl)benzene-1,3-diol was
supported by 1H and 13C NMR data (dH 3.58, 6.26, and 6.34; dC
68.6, 101.6, 109.4, 122.0, 138.3, 156.7, and 159.0) and HMBC corre-
lations of H-110a (dH 2.21) to C-50 (dC 138.3), C-60 (dC 109.4), and
C-100 (dC 122.0) indicating the connection of partial structure c
and C-50. The connectivity of C-40 and C-100 was assigned by a
HMBC correlation of H-30 (dH 7.08) to C-100.
The diastereotopic methylene protons (H2-11) at dH 2.82 and
3.01 were vicinally coupled with H-12 with respective J values of
H-11a (dd, J = 16.3, 16.3 Hz) and H-11b (d, J = 16.3 Hz), which indi-
cated that the former proton was pseudoaxial and the latter was
assignable to pseudoequatorial position. The relative configuration
of 1 was deduced through inspection of a molecular model as well
as the ROESY spectrum (Fig. 2), with ROESY correlations between
H-30/H-110b, H-110a/H3-130, and H3-130/H3-13 indicating a biphenyl
bond at C-40 and C-100 was S⁄-configuration and a secondary hy-
droxyl group at C-120 was R⁄-configuration, and a methyl group
at C-12 was S⁄-configuration as shown in Figure 2. Therefore, Cas-
sibiphenol A (1) was concluded to be a novel tetracycle connecting
5-(2-hydroxypropyl)benzene-1,3-diol.
Cassibiphenol B (2) was obtained as yellowish amorphous solid.
2 showed the similar CD curve and the same molecular formula as
1, C26H24O6, which was determined by HRESIMS [m/z 433.1653
(M+H)+, +0.2 mmu]. 1H and 13C NMR spectra are presented in Ta-
ble 1. The gross structure of 2 was deduced from extensive analysis
of the HMBC spectrum in CD3OD and revealed 2 had the same pla-
nar structure as 1 (Fig. 1). According to the similar CD data of 1 and
2, they were deduced to have the same absolute configuration at
C-12 and/or biphenyl configuration. The two possible relative con-
figurations of 2 were deduced through the difference of the 1H
NMR chemical shifts from H-110 to H-130 of 2 and 1 and ROESY cor-
relations between H-30/H-110a, and H-110a/H3-130 indicating 2 was
a steroisomer at C-120 or a rotational isomer of 1 (Fig. 3). The ste-
reochemistry of the secondary hydroxyl group of 1 and 2 could be
assigned by applying the Mosher method.13 However, the limited
amount of 1 and 2 prohibited the further investigation by the
chemical means.
1H NMR data [dH (J, Hz)] and 13C NMR Data [dC] of cassibiphenols A (1) and B (2) in
CD3OD at 300 K
Cassibiphenol A (1)
Cassibiphenol B (2)
Position dH
dC
dH
dC
2
3
4
5
6
7
158.1
113.5
166.8
137.5
123.1 6.41 (1H, s)
186.0
103.3 6.32 (1H, d, 1.4)
161.5
103.3
34.3 2.79 (1H, dd, 16.6, 13.4)
3.01 (1H, dd, 16.6, 2.9)
79.0 4.45 (1H, m)
20.2 1.16 (3H, d, 6.3)
117.7 7.44 (1H, s)
148.5
131.9 7.06 (1H, s)
139.0
138.3
157.7
113.3
166.8
137.7
123.2
185.9
103.3
161.7
103.3
34.5
6.41 (1H, s)
6.32 (1H, s)
8
9
10
11a
11b
12
13
14
20
2.82 (1H, dd, 16.3, 16.3)
3.01 (1H, d, 16.3)
4.41 (1H, m)
1.16 (3H, d, 6.1)
7.44 (1H, s)
79.5
20.2
117.7
148.2
132.4
139.2
139.3
109.1
158.9
101.3
156.5
121.8
44.1
30
7.08 (1H, s)
40
50
60
6.34 (1H, s)
6.26 (1H, s)
109.4 6.34 (1H, d, 2.0)
159.0
101.6 6.28 (1H, d, 2.0)
156.7
70
80
90
100
110a
110b
120
130
140
122.0
2.21 (1H, dd, 13.0, 5.4)
2.71 (1H, dd, 13.0, 5.4)
3.58 (1H, m)
1.01 (3H, d, 5.9)
2.55 (3H, s)
44.3 2.30 (1H, dd, 13.6, 6.2)
2.49 (1H, dd, 13.6, 6.2)
68.6 3.76 (1H, m)
22.9 0.95 (3H, d, 6.1)
22.0 2.54 (3H, s)
68.9
22.9
22.0
The gross structure of 1 was classified into two units, 3-methyl-
3H-isochromen-6(4H)-one (C-4 to C-13) and a biphenyl unit (C-2,
C-3, C-14, and C-20 to C-140), which were deduced from extensive
analysis of HMBC spectrum in CD3OD (Fig. 1).
Three partial structures, a (C-11 to C-13), b (C-14, C-20, C-30, and
C-140), and c (C-110 to C-130) were deduced from analysis of the
1H–1H COSY spectrum. Connection between partial structure a
and the dienone ring, which form 3-methyl-3H-isochromen-
6(4H)-one, could be assigned by HMBC correlations of H-6 (dH
6.41) to C-8 (dC 103.3), C-10 (dC 103.3), and C-11 (dC 34.3) and
H-8 (dH 6.32) to C-7 (dC 186.0), C-9 (dC 161.5), and C-10, and a four
bond HMBC correlation to C-4 (dC 166.8), and H-11a (dH 3.01) to
C-5 (dC 137.5) and C-10 (dC 103.3). Partial structure b in the
benzene ring, which connected with C-2 and C-3 through C-40
was indicated by HMBC correlations of H-14 (dH 7.44) to C-2 (dC
158.1) and C-3 (dC 113.5) and H-30 (dH 7.08) to C-3 and C-40 (dC
139.0). The ether linkage between C-2 and C-9 could be assigned
by the both down-field shifts of 13C NMR data; dC 161.5 and dC
158.1. The connection of C-3 and C-4 was deduced by the 13C
NMR chemical data of quaternary sp2 carbons; dC 113.5 and dC
Plausible biogenetic pathways for 1 and 2 were proposed as
shown in Scheme 1. 1 and 2 might be derived through a Michael
addition of 5-acetonyl-7-hydroxy-2-methylchromone14 producing
chrobisiamone A,15 followed by cleavage of an ether bond, cycliza-
tion with the
a,b-unsaturated ketone, and finally acid-promoted
ring disclosure16 to produce an isochromen part as shown in
Scheme 1.
Figure 1. Selected 2D NMR correlations for cassibiphenol A (1) and B (2).
Figure 2. Selected ROESY correlations for cassibiphenol A (1).