Y. Sadahiro et al. / Tetrahedron Letters 61 (2020) 151852
3
(
1
C-13), and 124.9 (C-3), nine heteroatom substituted carbons at d
C
0
0
0
07.3 (C-1 ), 89.8 (C-19), 76.4 (C-5 ), 75.1 (C-3 ), 74.1 (C-22), 73.1
0
0
0
(
C-2 ), 72.3 (C-5), 70.2 (C-4 ), and 62.4 (C-6 ), two methine carbons
at d 57.1 (C-17) and 54.4 (C-6), two quaternary carbons at d 47.1
C-1) and 41.9 (C-18), eight methylene carbons at d 44.3 (C-15),
2.4 (C-8), 41.6 (C-21), 29.2 (C-11), 29.2 (C-12), 28.9 (C-20), 26.2
28.7 (C-
C
C
(
4
(
C
C-16), and 26.1 (C-7), and eight methyl carbons at d
C
2
1
8), 25.4 (C-23), 23.3 (C-25), 23.0 (C-30), 22.0 (C-24), 16.4 (C-26),
6.3 (C-27), and 16.3 (C-29) (Table 1). The presence of a sugar unit
1
13
H
was indicated by characteristic H and C signals d 3.43–4.27 and
0
0
0
0
d
5
C
0
62.4–107.3. Two proton spin systems H-1 /H-2 /H-3 /H-4 and H-
0
0
0
2
/H -6 shown by COSY and HMBC correlations from H-5 to C-1
0
0
2
and from H -6 to C-4 showed a pyranose unit (Fig. 2a). The struc-
ture of the aglycone moiety of 1 was determined by a detailed
analysis of 2D NMR data. The COSY spectrum revealed five spin
Fig. 3. ECD spectra (MeCN) of pentabenzoates prepared from a commercially
available D-galactose and galactose liberated from 1 and 2.
systems (H-3/H-4, H-6/H
2
-7/H
-16/H-17, and H-19/H -20/H
-23 and H -24 to C-1, C-2, and C-6, from H-4 to C-2, and from
-25 to C-4, C-5, and C-6 showed the structure of a 5-substituted
2
-8, H-10/H
2 2
-11/H -12/H-13, H-15/
H
2
H
3
H
3
2
2
-21). HMBC correlations from
3
The relative configuration of the cyclohexenone unit was estab-
lished to be 5S*,6S*, which was determined by the NOE correlations
4
(
-hydroxy-4,6,6-trimethylcyclohex-2-en-1-one (C-1–C-8) moiety
Fig. 2a). Meanwhile, HMBC correlations from H -28 and H -29
-30 to C-17, C-21, and C-22, and
3 3 3 3
H-7b/H -24, H-7a/H -25, and H -24/H -25 on one side and H-6/
3
3
3
H -23 on the opposite site (Fig. 2d). The absolute configuration of
to C-17, C-18, and C-19, from H
from H-1 to C-19 indicated the structure of a 2-substituted
3
the cyclohexenone moiety was determined by the experimental
ECD spectrum compared with the calculated spectrum of a simpli-
fied model 5S,6S-3b [14]. The positive cotton effect at 236 nm of 1
matched with that of 5S,6S-3. Thus, the absolute configuration of
the cyclohexenone moiety of 1 was established (Fig. 4).
0
1
,3,3-trimethylcyclohexan-1-ol (C-15–C-22) moiety with a b-
galactose unit at C-19 (Fig. 2a). HMBC correlations from H -26 to
C-8, C-9, and C-10, and from H -27 to C-13, C-14, and C-15 con-
D-
3
3
nected the cyclohexane and cyclohexenone moieties through a
methylene unit (C-11–C-12) to complete the planar structure of
68
The molecular formula of compound 2, C44H O15, was deter-
1
13
mined by the HRESIMS. The H and C NMR spectra of 2 were sim-
1
(Fig. 2a). E geometries of the double bonds at C-9 and C-13 were
determined by the NOE correlations of H -8/H-10 and H-13/H -15.
The relative and absolute configurations were elucidated as fol-
ilar to those of 1 (Table 1), except for the presence of four acetoxy
2
2
0
groups (d
OAc); d
H
2.02 (8-OAc), 2.01 (11-OAc), 1.97 (22-OAc), and 1.93 (6 -
C
171.9–172.5 (4C)). Analysis of 2D NMR data indicated the
0
0
0
0
lows. Large coupling constants, H-1 /H-2 (J = 7.7 Hz) and H-2 /H-3
same carbon framework as 1. HMBC correlations, d
H
5.41 (H-11)/d
C
0
0
(
J = 9.5 Hz), and small coupling constants, H-3 /H-4 (J = 3.4 Hz),
together with NOE correlations of H-1 /H-3 , H-1 /H-5 , and H-3 /
H-5 indicated b-glycosylated galactose as
0
1
72.1 and d
H
4.14 and 4.34 (H
2
-6 )/d
C
172.5, clearly indicated that
0
0
0
0
0
0
two acetoxy groups were attached to C-11 (d
C
72.4) and C-6 (d
C
0
a pyranose unit
6
4.7). Although no HMBC correlation was observed from H-8 to
an acetoxy carbonyl carbon, the downfield H-8 (d 5.46, dd,
J = 9.3, 4.8 Hz) and C-8 (d 80.0) indicated the presence of an ace-
toxy group at C-8. These characteristic shifts matched well with
those of pouoside G (H-8: d 5.45, dd, J = 9.0, 5.0 Hz; C-8: d
0.0) [8], containing the same 5-substituted 4-hydroxy-4,6,6-
trimethylcyclohex-2-en-1-one (C-1–C-8) moiety. The remaining
acetoxy group was attached to a quaternary carbon C-22 (d
8.1) by the downfield shift, compared to that of 1 (d 74.1).
Pouoside A contains three acetoxy groups at C-8 (d 80.0),
C-11 (d 73.6), and C-22 (d 89.9) [7], and these shifts match with
(Fig. 2b). The absolute configuration of galactose was determined
H
from the ECD spectra. Galactose liberated from 1 by acid hydrolysis
was benzoylated, and the ECD spectrum of the product was identi-
cal to that of penta-O-benzoylgalactopyranoside prepared from a
C
H
C
commercially available
was therefore assigned as
D
-galactose [12] (Fig. 3). Galactose in 1
-series.
8
D
The 17S*,19S*, 22S* configuration of the cyclohexane unit was
determined by the NOE correlations (Fig. 2c). Namely, H-17, H-
C
8
C
1
3 3
9, and H-21b are on b face and H-20a, H -29, and H -30 are on
C
a
face. To determine the absolute configuration of the cyclohexane
C
C
unit, the modified Mosher’s method [13] was used with the acid
hydrolysate of 1, but this attempt failed because of decomposition
of the aglycone moiety by the acid hydrolysis.
(
a)
OH
6
HO
HO
25
8
2
7
2
8
29
3
5
'
O 1
'
1
0
O
9
1
8
14
O
1
3
5
0
13
1
2
2
HO
OH
23 24
2
6
OH
O
(
b)
(c)
(d)
OH
H
OH
H
H
17
H
6
H
H
23Me
Me
OH
5
5
'
O
19
H
O
1
'
O
16
25
Me
HO 3
'
H
H 2 9M e 22
OH
H
7
20
H
OH
H
b
H
a
H
H
H
Me 30
24Me
Fig. 2. COSY (bold lines), key HMBC (red arrows), and key NOESY (blue arrows)
correlations of compound 1 (a) and substructures (b), (c), and (d).
Fig. 4. Experimental ECD spectrum (MeCN) of 1 and calculated ECD spectrum of
5S,6S-3 with B3LYP/TZVP level.
Angkouw, Esther D.
