2. Results and Discussion
Felixin A (
1) was isolated as a white powder and the molecular formula for this compound was determined to be C
27H
42O
4 (seven unsaturations) using HRESIMS at
m/
z 453.29773 [M + Na]
+ (calcd for C
27H
42O
4 + Na, 453.29753). Comparison of the
13C NMR and DEPT data with the molecular formula indicated there must be an exchangeable proton, which required the presence of a hydroxy group. The IR spectrum of
1 showed strong bands at 3480, 1731 and 1662 cm
−1, consistent with the presence of hydroxy, ester and α,β-unsaturated ketone groups. The
13C NMR and DEPT spectral data showed that this compound has 27 carbons (
Table 1), including six methyls, nine sp
3 methylenes (including an oxymethylene), four sp
3 methines (including an oxymethine), four sp
3 quaternary carbons, an sp
2 methine and three sp
2 quaternary carbons (including two carbonyls). Based on the
1H and
13C NMR spectra (
Table 1),
1 was found to possess an acetoxy group (δ
H 2.08, 3H × s; δ
C 170.2, C; 21.5, CH
3) and a ketonic carbonyl (δ
C 199.1, C-24). An additional unsaturated functionality was indicated by
13C resonances at δ
C 139.4 (CH-16) and 137.7 (C-17), suggesting the presence of a trisubstituted olefin. Thus, from the above data, three degrees of unsaturation were accounted for and
1 was identified as a tetracyclic sesterterpenoid analogue.
Table 1.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 1.
Table 1.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 1.
Position | δH (J in Hz) | δC, Multiple | 1H–1H COSY | HMBC |
---|
1 | 2.09 m; 0.52 ddd (12.8, 12.8, 3.2) | 34.4, CH2 | H2-2 | C-3, -10, -22 |
2 | 1.51 m; 1.39 m | 17.8, CH2 | H2-1, H2-3 | n. o. a |
3 | 1.43 ddd (12.8, 4.0, 4.0) | 41.7, CH2 | H2-2 | C-1, -4, -5, -19, -20 |
| 1.17 ddd (12.8, 12.8, 4.8) | | | |
4 | | 33.0, C | | |
5 | 0.97 dd (12.0, 2.0) | 56.9, CH | H2-6 | C-3, -4, -6, -7, -9, -10, -20, -22 |
6 | 1.58 m; 1.45 m | 18.3, CH2 | H-5, H2-7 | C-5, -8 |
7 | 1.81 ddd (12, 8, 3.2, 3.2); 1.05 m | 41.9, CH2 | H2-6 | C-21 |
8 | | 37.4, C | | |
9 | 1.35 br d (13.2) | 53.1, CH | H2-11 | C-5, -7, -8, -10, -11, -12, -14, -21, -22 |
10 | | 41.8, C | | |
11 | 2.17 m; 1.96 m | 25.2, CH2 | H-9, H-12 | C-9, -13 |
12 | 4.72 dd (3.6, 2.0) | 77.1, CH | H2-11 | C-9, -14 |
13 | | 35.8, C | | |
14 | 1.56 m | 48.0, CH | H2-15 | C-7, -8, -13, -15, -21, -23 |
15 | 2.34 m; 2.22 m | 24.0, CH2 | H-14, H-16 | C-16, -17 |
16 | 6.86 m | 139.4, CH | H2-15 | C-14, -24 |
17 | | 137.7, C | | |
18 | 2.22 m; 1.92 m | 35.1, CH2 | | C-13, -14, -16, -17, -23, -24 |
19 | 0.87 s | 33.8, CH3 | | C-3, -4, -5, -20 |
20 | 0.77 s | 21.9, CH3 | | C-3, -4, -5, -19 |
21 | 1.10 s | 15.4, CH3 | | C-7, -8, -9, -14 |
22 | 4.03 d (11.6); 3.89 d (11.6) | 63.0, CH2 | | C-1, -9, -10 |
23 | 0.87 s | 19.6, CH3 | | C-12, -13, -14 |
24 | | 199.1, C | | |
25 | 2.28 s | 25.2, CH3 | | C-17, -24 |
12-OAc | | 170.2, C | | |
| 2.08 s | 21.5, CH3 | | Acetate carbonyl |
From the
1H–
1H COSY spectrum of
1 (
Table 1), it was possible to establish the separate system that map out the proton sequences from H
2-1/H
2-2/H
2-3, H-5/H
2-6/H
2-7, H-9/H
2-11/H-12 and H-14/H
2-15/H-16. These data, together with the key HMBC correlations between protons and quaternary carbons (
Table 1), such as H
2-3, H-5, H
3-19, H
3-20/C-4; H
2-6, H-9, H-14, H
3-21/C-8; H
2-1, H-5, H-9, H
2-22/C-10; H
2-11, H-14, H
2-18, H
3-23/C-13; H
2-15, H
2-18, H
3-25/C-17; and H-16, H
2-18, H
3-25/C-24, established the carbon skeleton of
1 as a 24-homo-25-norscalarane derivative [
13]. The oxymethylene unit at δ
C 63.0 was correlated to the methylene protons at δ
H 4.03 and 3.89 in the HMQC spectrum. The methylene signals were
2J-correlated with C-10 (δ
C 41.8) and
3J-correlated with both C-1 (δ
C 34.4) and C-9 (δ
C 53.1), proving the attachment to a hydroxymethyl group at C-10 (
Table 1). Thus, the remaining acetoxy group was positioned at C-12, an oxymethine (δ
H 4.72, δ
C 77.1) as indicated by analysis of the
1H–
1H COSY correlations and characteristic NMR signals, although no HMBC correlation was observed between H-12 and the acetate carbonyl.
The relative stereochemistry of
1 was elucidated from the NOE interactions observed in an NOESY experiment (
Figure 2). As per convention, when analyzing the stereochemistry of scalarane sesterterpenoids, H-5 and hydroxymethyl at C-10 were assigned to the α and β face, anchoring the stereochemical analysis because no correlation was found between H-5 and H
2-22. In the NOESY experiment of
1, H-9 showed correlations with H-5 and H-14 but not with H
3-21 and H
2-22. Thus, both H-9 and H-14 must also be on α face whilst Me-21 and the hydroxymethyl at C-10 must be located on the β face. Moreover, the correlations of H
3-23/H
3-21 and H
3-23/H-12, indicated the β-orientation of Me-23 and H-12 attaching at C-13 and C-12, respectively. The NOESY spectrum showed a correlation of H-16 with H
3-25, revealing the
E geometry of the C-16/17 double bond. Based on the above findings, the structure, including the relative configuration of
1 was established unambiguously.
Figure 2.
Selective NOESY correlations of 1.
Figure 2.
Selective NOESY correlations of 1.
The HRESIMS of
2 (felixin B) exhibited a pseudomolecular ion peak at
m/
z 467.27707 [M + Na]
+, with the molecular formula C
27H
40O
5 (calcd C
27H
40O
5 + Na, 467.27680), implying eight degrees of unsaturation. The IR absorptions of
2 showed the presence of hydroxy (3501 cm
−1), ester carbonyl (1733 cm
−1) and α,β-unsaturated ketone (1679 cm
−1) functionalities. The
13C NMR and DEPT spectrum of
2 exhibited for all 27 carbons: two ketones (δ
C 197.9, C-24; 197.7, C-16), an ester carbonyl (δ
C 170.2, acetate carbonyl), a trisubstituted olefin (δ
C 163.9, CH-18; 136.6, C-17), an oxymethylene (δ
C 62.7, CH
2-22), an oxymethine (δ
C 76.3, CH-12), six methyls, seven methylenes, three methines and four quaternary carbons. Both the
13C and
1H NMR data for the rings A–C portions were essentially same as those of
1. It also contained an acetoxy (δ
H 2.05), an acetyl (methyl ketone, δ
H 2.42) and a hydroxymethyl (δ
H 4.04 and 3.87) groups as in
1. Analysis of
1H–
1H COSY and HMBC data (
Table 2) revealed the planar structure. The same stereochemistry was shown by coupling constant and NOE data (
Figure 3). The NOESY spectrum showed correlations of H-18 with H-12 and H
3-23, revealing the
Z geometry of the C-17/18 double bond.
Table 2.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 2.
Table 2.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 2.
Position | δH (J in Hz) | δC, Multiple | 1H–1H COSY | HMBC |
---|
1 | 2.11, m; 0.53 ddd (13.2, 13.2, 4.0) | 34.2, CH2 | H2-2 | C-2, -3, -10, -22 |
2 | 1.58–1.42 m | 18.3, CH2 | H2-1, H2-3 | n. o. a |
3 | 1.42 m; 1.19 m | 41.6, CH2 | H2-2 | C-4, -20 |
4 | | 33.0, C | | |
5 | 0.96 m | 57.0, CH | H2-6 | C-3, -4, -6, -7, -9, -10, -20, -22 |
6 | 1.54 m; 1.42 m | 17.7, CH2 | H-5, H2-7 | n. o. |
7 | 1.78 ddd (12.8, 3.2, 3.2); 1.05 m | 41.0, CH2 | H2-6 | C-21 |
8 | | 37.2, C | | |
9 | 1.31 br d (13.2) | 53.1, CH | H2-11 | C-5, -7, -8, -10, -11, -21, -22 |
10 | | 41.7, C | | |
11 | 2.29 ddd (13.6, 13.6, 2.4); 2.05 m | 24.9, CH2 | H-9, H-12 | n. o. |
12 | 4.97 dd (2.8, 2.8) | 76.3, CH | H2-11 | n. o. |
13 | | 41.4, C | | |
14 | 2.11 m | 48.9, CH | H2-15 | C-8, -13, -21, -23 |
15 | 2.57–2.40 m | 35.0, CH2 | H-14 | C-13, -14, -16 |
16 | | 197.7, C | | |
17 | | 136.6, C | | |
18 | 7.30 s | 163.9, CH | | C-12, -14, -17, -24 |
19 | 0.87 s | 33.8, CH3 | | C-3, -4, -5, -20 |
20 | 0.76 s | 21.8, CH3 | | C-3, -4, -5, -19 |
21 | 1.12 s | 15.7, CH3 | | C-7, -8, -9, -14 |
22 | 4.04 d (12.0); 3.87 d (12.0) | 62.7, CH2 | | C-1, -9, -10 |
23 | 1.17 s | 18.4, CH3 | | C-12, -13, -14, -18 |
24 | | 197.9, C | | |
25 | 2.42 s | 30.6, CH3 | | C-17, -24 |
12-OAc | | 170.2, C | | |
| 2.05 s | 21.2, CH3 | | Acetate carbonyl |
Figure 3.
Selective NOESY correlations of 2.
Figure 3.
Selective NOESY correlations of 2.
Felixin C (
3) was isolated as a white solid. Its HRESIMS (
m/
z 469.29290 [M + Na]
+) and NMR data (
Table 3) established a molecular formula of C
27H
42O
5 (calcd C
27H
42O
5 + Na, 469.29245). The IR spectrum of
3 revealed the presence of hydroxy (
νmax 3480 cm
−1) ester (
νmax 1731 cm
−1) and α,β-unsaturated ketone (
νmax 1662 cm
−1) groups. By comparison of NMR data of
3 with those of
2 (
Table 2 and
Table 3), it was found that the ketone at C-16 in
2 (δ
C 197.7) was replaced by a hydroxy group (δ
C 63.3, δ
H 4.55, 1H,
J = 3.6 Hz) in
3. Analyses of
1H–
1H COSY and HMBC correlations established the planar structure of
3 (
Table 3) as shown in
Figure 1, which showed the C-16 positioning of the hydroxy group. Careful analysis of the NOESY spectrum of
3, in comparison with that of
2, allowed determination of the relative stereochemistry of A–C rings of felixin C (
3) as shown in
Figure 4. Moreover, the splitting pattern and
J-value of proton at C-16 in
3, combined with the interactions observed between H-16 and both of the C-15 methylene protons revealed the α-orientation of the 16-OH. Furthermore, the correlations between the olefinic proton H-18/H
3-23 and H-18/H-12 assigned the
E-configuration of the double bond between C-17 and C-18.
Table 3.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 3.
Table 3.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 3.
Position | δH (J in Hz) | δC, Multiple | 1H–1H COSY | HMBC |
---|
1 | 2.08 m; 0.57 ddd (12.8, 12.8, 3.2) | 34.1, CH2 | H2-2 | n. o. a |
2 | 1.54 m; 1.39 m | 17.8, CH2 | H2-1, H2-3 | n. o. |
3 | 1.42 m; 1.16 m | 41.7, CH2 | H2-2 | C-20 |
4 | | 33.0, C | | |
5 | 1.02 dd (12.8, 2.4) | 56.8, CH | H2-6 | C-4, -20, -22 |
6 | 1.54 m; 1.47 m | 18.4, CH2 | H-5, H2-7 | n. o. |
7 | 1.88 m; 1.11 m | 41.3, CH2 | H2-6 | C-8, -21 |
8 | | 36.8, C | | |
9 | 1.45 m | 53.5, CH | H2-11 | C-10, -11, -21, -22 |
10 | | 41.8, C | | |
11 | 1.96–1.81 m | 25.3, CH2 | H-9, H-12 | C-8, -10, -13 |
12 | 4.97 dd (2.8, 2.8) | 76.5, CH | H2-11 | n. o. |
13 | | 41.4, C | | |
14 | 1.88 m | 44.0, CH | H2-15 | C-8, -13, -15, -16, -21, -23 |
15 | 1.88 m; 1.64 dd (14.0, 4.8) | 25.3, CH2 | H-14, H-16 | C-8, -13, -16, -17 |
16 | 4.55 d (3.6) | 63.3, CH | H2-15 | C-14, -17, -18 |
17 | | 138.2, C | | |
18 | 6.59 s | 152.2, CH | | C-12, -13, -14, -16, -24 |
19 | 0.85 s | 33.8, CH3 | | C-3, -4, -5, -20 |
20 | 0.76 s | 21.8, CH3 | | C-3, -4, -5, -19 |
21 | 1.06 s | 16.4, CH3 | | C-7, -8, -9, -14 |
22 | 4.04 d (12.0); 3.90 d (12.0) | 62.8, CH2 | | C-1, -9, -10 |
23 | 1.06 s | 19.5, CH3 | | C-12, -13, -14, -18 |
24 | | 201.4, C | | |
25 | 2.24 s | 25.4, CH3 | | C-17, -24 |
12-OAc | | 170.9, C | | |
| 2.04 s | 21.4, CH3 | | Acetate carbonyl |
Figure 4.
Selective NOESY correlations of 3.
Figure 4.
Selective NOESY correlations of 3.
Moreover, two deoxoscalarin-like metabolites [
13], felixins D (
4) and E (
5) were isolated from
I. felix in this study. Felixin D (
4) was isolated as white powder and its molecular formula was established as C
30H
46O
6 from the HRESIMS at
m/
z 525.31849 (calcd C
30H
46O
6 + Na, 525.31866). Eight degrees of unsaturation implied by the molecular formula were ascribed to five rings, a trisubstituted double bond (δ
C 141.2, C-17; 114.4, CH-16) and two ester carbonyl groups (δ
C 171.0, 170.9, 2 × C). The
1H NMR spectrum showed seven methyls (δ
H 2.10, 2.05, 2 × 3H, s, acetate methyls; 1.26, 3H, d,
J = 6.0 Hz, H
3-26; 0.98, 3H, s, H
3-23; 0.89, 3H, s, H
3-21; 0.83, 3H, s, H
3-22; 0.78, 3H, s, H
3-25); an acetoxymethylene (δ
H 4.59, 1H, d,
J = 12.0 Hz; 4.16, 1H, d,
J = 12.0 Hz, H
2-24); three oxymethines (δ
H 5.21, 1H, d,
J = 3.2 Hz, H-19; 4.91, 1H, dd,
J = 3.2, 2.4 Hz, H-12; 4.62, 1H, br s, H-20); and an olefinic proton (δ
H 5.35, 1H, br s, H-16). The
13C NMR and DEPT spectra exhibited 30 signals, including seven methyls, eight sp
3 methylenes (including an oxymethylene), seven sp
3 methines (including three oxymethines), an sp
2 methine, four sp
3 quaternary carbons and three sp
2 quaternary carbons (including two ester carbonyls). A typical sesterterpenoid carbons system bearing an acetoxymethylene and four methyl groups along rings A–D could be established by the HMBC correlations from the acetoxymethylene (CH
2-24) and four methyl groups (Me-21, 22, 23 and 25) to the associated carbons and a deoxoscalarin skeleton could be obtained on the basis of further HMBC and
1H–
1H COSY correlations (
Table 4). The
1H–
1H COSY correlations between H-18/H-19 and H-20/H
3-26 and the HMBC correlations from H-19/C-20 and H
3-26/C-17, -20, allowed the establishment of the hemiacetal ring E.
The relative stereochemistry of
4 was elucidated from the interactions observed in an NOESY experiment (
Figure 5). In the NOESY experiment of
1, H-9 showed correlations with H-5 and H-14, but not with H
3-23 and H
2-24 at C-10. Thus, both H-5 and H-14 must be on α face whilst Me-23 and the acetoxymethylene at C-10 must be located on the β face. The correlations of H
3-25 with H
3-23 and H-12 indicated the β-orientation of Me-25 and H-12. H-18 correlated with H-14, but not with H-19, and H-19 correlated with H-12 and H
3-25, assuming that H-18 and H-19 were α- and β-oriented, respectively. H-16 showed correlations with H-20 and H
3-26, but not with H-18, revealing the
E geometry of the C-16/17 double bond. It was found that the structure of
4 was similar with that of a known scalarane, 12-deacetyl-23-acetoxy-20-methyl-12-
epi-deoxo- scalarin (
6) [
14], excepting the β-hydroxy group at C-12 in
6 was replaced by an α-acetoxy group in
4. The relative configuration of C-20 chiral carbon in
4 was elucidated by comparison the NMR data of CH-20 (δ
H 4.62, 1H, m; δ
C 74.0) of
4 with those of
6 (δ
H 4.67, 1H, m; δ
C 74.5), indicating H-20 in
4 was α-oriented.
Table 4.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 4.
Table 4.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 4.
Position | δH (J in Hz) | δC, Multiple | 1H–1H COSY | HMBC |
---|
1 | 1.98 dd (13.2, 2.4) | 34.7, CH2 | H2-2 | C-5, -9, -24 |
| 0.57 ddd (13.2, 13.2, 2.4) | | | |
2 | 1.56 m; 1.43 m | 18.2, CH2 | H2-1, H2-3 | C-4 |
3 | 1.46 m; 1.15 m | 41.6, CH2 | H2-2 | C-2, -4, -21, -22 |
4 | | 33.0, C | | |
5 | 1.04 dd (12.8, 2.0) | 56.8, CH | H2-6 | C-3, -4, -6, -7, -9, -10, -21, -22, -24 |
6 | 1.56 m; 1.38 dd (13.6, 3.2) | 17.9, CH2 | H-5, H2-7 | n. o. a |
7 | 1.79 ddd (12.8, 3.2, 3.2); 1.12 m | 41.7, CH2 | H2-6 | C-5, -8, -9, -14, -23 |
8 | | 37.7, C | | |
9 | 1.46 m | 52.9, CH | H2-11 | C-1, -5, -8, -10, -11, -12, -14, -23, -24 |
10 | | 40.1, C | | |
11 | 2.05–1.89 m | 25.1, CH2 | H-9, H-12 | C-8 |
12 | 4.91 dd (3.2, 2.4) | 74.6, CH | H2-11 | C-9, -14, acetate carbonyl |
13 | | 36.9, C | | |
14 | 1.64 dd (11.2, 6.4) | 50.4, CH | H2-15 | C-7, -8, -9, -13, -15, -18, -25 |
15 | 2.16 m; 1.97 m | 22.9, CH2 | H-14, H-16 | C-8 |
16 | 5.35 br s | 114.4, CH | H2-15 | n. o. |
17 | | 141.2, C | | |
18 | 2.82 br s | 54.7, CH | H-19 | n. o. |
19 | 5.21 d (3.2) | 96.7, CH | H-18 | C-20 |
20 | 4.62 m | 74.0, CH | H3-26 | n. o. |
21 | 0.89 s | 33.7, CH3 | | C-3, -4, -5, -22 |
22 | 0.83 s | 21.9, CH3 | | C-3, -5, -21 |
23 | 0.98 s | 15.4, CH3 | | C-7, -9, -14 |
24 | 4.59 d (12.0); 4.16 d (12.0) | 64.9, CH2 | | C-1, -9, -10, acetate carbonyl |
25 | 0.78 s | 14.7, CH3 | | C-12, -14, -18 |
26 | 1.26 d (6.0) | 17.6, CH3 | H-20 | C-17, -20 |
12-OAc | | 170.9, C | | |
| 2.10 s | 21.5, CH3 | | Acetate carbonyl |
23-OAc | | 171.0, C | | |
| 2.05 s | 21.2, CH3 | | Acetate carbonyl |
Figure 5.
Selective NOESY correlations of 4.
Figure 5.
Selective NOESY correlations of 4.
The HRESIMS of
5 (felixin E) exhibited a pseudomolecular ion peak at
m/
z 441.29739 [M + Na]
+, with the molecular formula C
26H
42O
4 (calcd C
26H
42O
4 + Na, 441.29753), implying six degrees of unsaturation. The IR absorptions of
5 showed the presence of hydroxy (3421 cm
−1) and ketone (1701 cm
−1) functionalities. The
13C NMR and DEPT spectrum of
5 exhibited for all 26 carbons: a ketone (δ
C 219.0, C-12), a hemiacetal (δ
C 97.1, CH-19), two oxymethines (δ
C 78.1, CH-20; 72.0, CH-16), six methyls, seven methylenes, five methines, and four quaternary carbons (
Table 5). The NMR data of
5 were similar with those of
4, except for the acetoxymethylene group at C-10 and acetoxy group at C-12 in
4 were replaced by a methyl and a ketone group in
5, respectively. The C-16/17 trisubstituted olefin in
4 was replaced by a hydroxy group at C-16 in
5. The stereochemical configuration was identical to that of other scalarane sesterterpenes based on NOESY cross-peaks at H-5/H-9, H-9/H-14, H-14/H-16, H-14/H-18, H-16/H-18, H-16/H-20, H-19/H
3-25, H
3-22/H
3-24, H
3-23/H
3-24 and H
3-23/H
3-25 (
Figure 6). Furthermore, it was found that the structure of
5 was similar with that of known scalarane
7 [
15], excepting the 12α-acetoxy group in
7 was replaced by a ketone group in
5.
Table 5.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 5.
Table 5.
1H (400 MHz, CDCl3) and 13C (100 MHz, CDCl3) NMR data and 1H–1H COSY and HMBC correlations for scalarane 5.
Position | δH (J in Hz) | δC, Multiple | 1H–1H COSY | HMBC |
---|
1 | 1.56 m; 0.76 m | 39.3 CH2 | H2-2 | C-5 |
2 | 1.64–1.34 m | 18.3, CH2 | H2-1, H2-3 | n. o. a |
3 | 1.80 m; 1.38 m | 41.6, CH2 | H2-2 | n. o. |
4 | | 33.3, C | | |
5 | 0.94 m | 56.5, CH | H2-6 | C-4 |
6 | 1.64–1.34 m | 18.1, CH2 | H-5, H2-7 | n. o. |
7 | 1.81 m; 0.94 dd (13.2, 4.0) | 41.7, CH2 | H2-6 | C-5 |
8 | | 37.8, C | | |
9 | 1.19 m | 61.4, CH | H2-11 | C-8, -12, -14, -23 |
10 | | 38.2, C | | |
11 | 2.70 dd (14.0, 13.2); 2.32 dd (13.2, 2.4) | 35.3, CH2 | H-9 | C-8, -9, -12 |
12 | | 219.0, C | | |
13 | | 51.2, C | | |
14 | 1.21 m | 59.2, CH | H2-15 | C-12, -18 |
15 | 1.95 ddd (12.8, 4.4, 2.4); 1.41 m | 30.8, CH2 | H-14, H-16 | C-13 |
16 | 3.55 ddd (10.4, 10.4, 4.8) | 72.0, CH | H2-15, H-17 | n. o. |
17 | 1.62 m | 53.0, CH | H-16, H-18, H-20 | n. o. |
18 | 1.86 m | 59.2, CH | H-17, H-19 | C-13, -16, -19, -25 |
19 | 5.31 d (6.0) | 97.1, CH | H-18 | C-18, -20 |
20 | 4.10 qd (6.0, 3.2) | 78.1, CH | H-17, H3-26 | n. o. |
21 | 0.85 s | 33.2, CH3 | | C-3, -4, -5, -22 |
22 | 0.82 s | 21.3, CH3 | | C-4, -21 |
23 | 1.06 s | 16.9, CH3 | | C-7, -8, -9, -14 |
24 | 0.87 s | 15.6, CH3 | | C-10 |
25 | 1.24 s | 15.3, CH3 | | C-12, -13, -14, -18 |
26 | 1.38 d (6.0) | 20.5, CH3 | H-20 | C-17, -20 |
Figure 6.
Selective NOESY correlations of 5.
Figure 6.
Selective NOESY correlations of 5.
The cytotoxicity of compounds
1–
5 against MOLT-4 (human acute lymphoblastic leukemia), SUP-T1 (human T-cell lymphoblastic lymphoma), DLD-1 (human colorectal adenocarcinoma), LNCaP (human prostatic carcinoma), T-47D (human ductal carcinoma) and MCF7 (human breast adenocarcinoma) tumor cells are shown in
Table 6. The results showed that compounds
1–
5 were found to exhibit cytotoxicity against DLD-1 tumor cells. By comparison with the structures and cytotoxicity of scalaranes
2 and
3, implying that the presence of 16-ketone would enhance the activity.
Table 6.
Cytotoxic data of scalarane sesterterpenoids 1–5.
Table 6.
Cytotoxic data of scalarane sesterterpenoids 1–5.
Compounds | Cell Lines IC50 (μM) |
---|
MOLT-4 | SUP-T1 | DLD-1 | LNCaP | T-47D | MCF7 |
---|
1 | NA b | NA | 10.9 | 24.3 | NA | NA |
2 | 14.9 | 27.1 | 8.5 | NA | 32.2 | 23.0 |
3 | 18.5 | NA | 15.0 | NA | NA | NA |
4 | 12.8 | 31.6 | 7.9 | 21.5 | 20.2 | NA |
5 | 14.0 | 31.1 | 7.2 | NA | 22.7 | 24.3 |
Doxorubicin a | 0.02 | 0.09 | 0.64 | 0.02 | 0.09 | 0.79 |