Journal of Natural Products
ARTICLE
excess of Zn metal (30 mg). The reaction was stirred for 16 h at room
temperature, then filtered, and the solution dried under reduced
pressure to obtain a synthetic sample of seco-plakortolide K (10)
(0.4 mg) in close to quantitative yield. Plakortolide L (2) (1.8 mg,
4.3 μmol) was subjected to the same experimental procedure to provide
a synthetic sample of seco-plakortolide L (11) (1.5 mg).
H-23), 1.40 (1H, d, J = 15.0 Hz, H-5b), 1.24-1.32 (20H, m, H-7 to
H-16), 0.84 (3H, s, H-24); HRESIMS m/z 589.3520 [M þ Na]þ (calcd
for C35H50NaO6, 589.3500).
Plakortone L (14): colorless oil; 1H NMR (CDCl3, 500 MHz) was
identical to the sponge-derived sample of plakortone ether L; LRESIMS
m/z 423.3 [M þ Na]þ.
1
seco-Plakortolide K (10): colorless oil; H NMR (CDCl3, 500
Reductive Cleavage of Plakortolide M (3) and Plakortolide
N (4). Samples of plakortolide M (3) (2.3 mg) or plakortolide N (4)
(2 mg) were subjected to Zn/AcOH reduction using the same experi-
mental procedure as above to provide samples of seco-plakortolide M
(22) (1.3 mg) and seco-plakortolide N (23) (1.1 mg).
MHz) was identical to the natural sample of seco-plakortolide K;
LRESIMS m/z 441.3 [M þ Na]þ.
seco-Plakortolide L (11): colorless oil; [R]D -10.9 (c 0.1,
1
CHCl3); H NMR (CDCl3, 500 MHz) was identical to the natural
sample of seco-plakortolide L; LRESIMS m/z 441.3 [M þ Na]þ.
Preparation of MPA Esters of seco-Plakortolide K (20a/
20b) and seco-Plakortolide L (21a/21b). The sample of seco-
plakortolide K (10) (0.4 mg) obtained by Zn/AcOH reduction of
plakortolide K was divided in half, and each sample (approximately
0.2 mg) was treated with either (R)- or (S)-MPA (1 mg, 2 equiv),
followed by DCC (1 mg, 2 equiv) and DMAP (0.6 mg, 2 equiv) in dry
CH2Cl2 (0.5 mL). The reaction was stirred overnight at room tempera-
ture before filtering through a small plug of silica eluting with CHCl3
(5 mL). The solvent was then removed in vacuo, and the product MPA
esters were then individually purified by RP-HPLC using an analytical
column and eluting with CH3CN/H2O (9:1) to obtain respectively
the (R)-MPA ester (20a) (0.1 mg) and (S)-MPA ester (20b) (0.1 mg).
A sample of seco-plakortolide L (11) (1.5 mg), obtained by Zn/AcOH
reduction of plakortolide L, was likewise divided in half, and each sample
(approximately 0.8 mg) reacted with either (R)- or (S)-MPA using
the same procedure yielding (R)-MPA ester (21a) (0.4 mg) and
(S)-MPA ester (21b) (0.5 mg). Trace amounts of plakortone L (14)
(approximately 0.1 mg) were identified during the RP-HPLC of the
esterification products derived from 11.
seco-Plakortolide M (22): colorless oil; [R]D þ21 (c 0.09,
1
CHCl3); H and 13C NMR (CDCl3, 500 MHz), see Tables 3 and 4;
HRESIMS m/z 457.2925 [M þ Na]þ (calcd for C26H42NaO4,
457.2924).
seco-Plakortolide N (23): colorless oil; [R]D þ13 (c 0.08,
1
CHCl3); H and 13C NMR (CDCl3, 500 MHz), see Tables 3 and 4;
HRESIMS m/z 457.2939 [M þ Na]þ (calcd for C26H42NaO4,
457.2924).
Preparation of MPA Diesters (24a/b and 24a/b) of seco-
Plakortolide M (22) and seco-Plakortolide N (23) from 3
and 4. Mosher ester preparation used the same experimental proce-
dures as for 20a/20b and 21a/21b except that three equivalents of
reagents were used to ensure esterification of the terminal phenolic group.
The Mosher ester products were purified by RP-HPLC using an analytical
column and eluting with CH3CN/H2O (9:1) to obtain respectively the
(R)-MPA ester (24a) (0.2 mg) and (S)-MPA ester (24b) (0.2 mg) from
seco-plakortolide M (22) and the (R)-MPA ester (25a) (0.2 mg) and (S)-
MPA ester (25b) (0.1 mg) from seco-plakortolide N (23). During the
HPLC purifications, samples of plakortone N (15), the 22-O-(S)-MPA
ester of plakortone N (26), and plakortone M (27), each <0.2 mg in
weight, were isolated from the reactions with 23 and 22, respectively.
(R)-MPA diester (24a): colorless oil; 1H NMR (CDCl3, 500
MHz) δ 7.53 (2H, m, MPA phenyl protons), 7.33-7.41 (8H, m,
MPA phenyl protons), 7.10 (2H, d, J = 8.5 Hz, H-20), 6.86 (2H, d, J = 8.5
Hz, H-21), 5.18 (1H, dd, J = 6.2, 1.2 Hz, H-3), 4.97 (1H, s, CH of MPA),
4.74 (1H, s, CH of MPA), 3.49 (3H, s, OMe), 3.36 (3H, s, OMe), 3.03
(1H, dd, J = 18.6, 6.2 Hz, H-2a), 2.54 (2H, t, 7.6 Hz, H-18), 2.47 (1H, dd,
J = 18.6, 1.2 Hz, H-2b), 1.55 (2H, m, H-17), 1.49 (1H, d, J = 15.1 Hz,
H-5a), 1.39 (1H, d, J = 15.1 Hz, H-5b), 1.48 (3H, s, H-23), 1.22-1.28
(14H, m, H-9 to H-16), 1.09 (3H, s, H-24), 1.08 (2H, m, H-7), 1.07 (2H,
m, H-8); HRESIMS m/z 753.3975 [M þ Na]þ (calcd for C44H58NaO9,
753.3973).
(R)-MPA ester (20a): colorless oil; 1H NMR (CDCl3, 500 MHz)
δ 7.33-7.42 (5H, m, MPA phenyl protons), 7.25 (2H, m, H-21), 7.16
(2H, m, H-20), 7.15 (1H, m, H-22), 5.19 (1H, dd, J = 6.5, 1.5 Hz, H-3),
4.74 (1H, s, CH of MPA), 3.36 (3H, s, OMe), 3.03 (1H, dd, J = 18.5, 6.5
Hz, H-2a), 2.58 (2H, t, 7.5 Hz, H-18), 2.47 (1H, dd, J = 18.5, 1.5 Hz,
H-2b), 1.49 (3H, s, H-23), 1.49 (1H, d, J = 15.0 Hz, H-5a), 1.39 (1H, d,
J = 15.0 Hz, H-5b), 1.24-1.32 (22H, m, H-7 to H-17), 1.10 (3H, s,
H-24); HRESIMS m/z 589.3498 [M þ Na]þ (calcd for C35H50NaO6,
589.3500).
(S)-MPA ester (20b): colorless oil; 1H NMR (CDCl3, 500 MHz)
δ 7.33-7.42 (5H, m, MPA phenyl protons), 7.25 (2H, m, H-21), 7.16
(2H, m, H-20), 7.15 (1H, m, H-22), 5.21 (1H, dd, J = 6.5, 1.5 Hz, H-3),
4.78 (1H, s, CH of MPA), 3.39 (3H, s, OMe), 2.94 (1H, dd, J = 18.5, 6.5
Hz, H-2a), 2.58 (2H, t, 7.5 Hz, H-18), 2.22 (1H, dd, J = 18.5, 1.5 Hz,
H-2b), 1.82 (1H, d, J = 15.0 Hz, H-5a), 1.78 (1H, d, J = 15.0 Hz, H-5b),
1.53 (3H, s, H-23), 1.26 (3H, s, H-24), 1.24-1.32 (22H, m, H-7 to
H-17); HRESIMS m/z 589.3597 [M þ Na]þ (calcd for C35H50NaO6,
589.3500).
(S)-MPA diester (24b): colorless oil; 1H NMR (CDCl3, 500
MHz) δ 7.53 (2H, m, MPA phenyl protons), 7.33-7.41 (8H, m,
MPA phenyl protons), 7.10 (2H, d, J = 8.5 Hz, H-20), 6.86 (2H, d, J = 8.5
Hz, H-21), 5.21 (1H, dd, J = 6.3, 1.5 Hz, H-3), 4.97 (1H, s, CH of MPA),
4.78 (1H, s, CH of MPA), 3.48 (3H, s, OMe), 3.39 (3H, s, OMe), 2.94
(1H, dd, J = 18.6, 6.3 Hz, H-2a), 2.54 (2H, t, 7.9 Hz, H-18), 2.22 (1H, dd,
J = 18.6, 1.5 Hz, H-2b), 1.81 (1H, d, J = 15. 0 Hz, H-5a), 1.78 (1H, d, J =
15.1 Hz, H-5b), 1.54 (2H, m, H-17), 1.54 (3H, s, H-23), 1.25 (3H, s,
H-24), 1.36 (2H, m, H-7), 1.22-1.26 (18H, m, H-8 to H-16);
HRESIMS m/z 753.3952 [M þ Na]þ (calcd for C44H58NaO9,
753.3973).
(R)-MPA ester (21a): colorless oil; 1H NMR (CDCl3, 500 MHz)
δ 7.33-7.42 (5H, m, MPA phenyl protons), 7.25 (2H, m, H-21), 7.16
(2H, m, H-20), 7.15 (1H, m, H-22), 5.19 (1H, dd, J = 6.5, 2.0 Hz, H-3),
4.79 (1H, s, CH of MPA), 3.40 (3H, s, OMe), 2.94 (1H, dd, J = 18.5, 6.5
Hz, H-2a), 2.58 (2H, t, 8.0 Hz, H-18), 2.25 (1H, dd, J = 18.5, 2.0 Hz,
H-2b), 1.92 (1H, d, J = 15.0 Hz, H-5a), 1.76 (1H, d, J = 15.0 Hz, H-5b),
1.59 (2H, m, H-17), 1.53 (3H, s, H-23), 1.47 (2H, m, H-7), 1.24-1.32
(20H, m, H-8 to H-16), 1.13 (3H, s, H-24); HRESIMS m/z 589.3518
[M þ Na]þ (calcd for C35H50NaO6, 589.3500).
(R)-MPA diester (25a): colorless oil; 1H NMR (CDCl3, 500
MHz) δ 7.53 (2H, m, MPA phenyl protons), 7.33-7.40 (8H, m,
MPA phenyl protons), 7.10 (2H, d, J = 8.5 Hz, H-20), 6.86 (2H, d, J = 8.5
Hz, H-21), 5.19 (1H, dd, J = 6.4, 1.8 Hz, H-3), 4.97 (1H, s, CH of MPA),
4.78 (1H, s, CH of MPA), 3.48 (3H, s, OMe), 3.39 (3H, s, OMe), 2.94
(1H, dd, J = 18.6, 6.4 Hz, H-2a), 2.53 (2H, t, 7.8 Hz, H-18), 2.25 (1H, dd,
J = 18.5, 1.8 Hz, H-2b), 1.91 (1H, d, J = 15.1 Hz, H-5a), 1.76 (1H, d, J =
15.1 Hz, H-5b), 1.48-1.55 (4H, m, H-7 and H-8), 1.55 (3H, s, H-23),
1.22-1.28 (14H, m, H-9 to H-16), 1.13 (3H, s, H-24); HRESIMS m/z
753.3947 [M þ Na]þ (calcd for C44H58NaO9, 753.3973).
(S)-MPA ester (21b): colorless oil; 1H NMR (CDCl3, 500 MHz)
δ 7.33-7.42 (5H, m, MPA phenyl protons), 7.25 (2H, m, H-21), 7.16
(2H, m, H-20), 7.15 (1H, m, H-22), 5.19 (1H, dd, J = 6.2, 1.5 Hz, H-3),
4.74 (1H, s, CH of MPA), 3.36 (3H, s, OMe), 3.02 (1H, dd, J = 18.6, 6.2
Hz, H-2a), 2.58 (2H, t, 7.8 Hz, H-18), 2.47 (1H, dd, J = 18.6, 1.5 Hz,
H-2b), 1.59 (1H, d, J = 15. 0 Hz, H-5a), 1.59 (2H, m, H-17), 1.48 (3H, s,
206
dx.doi.org/10.1021/np100620x |J. Nat. Prod. 2011, 74, 194–207