Isolation of pandamarilactonine-H from the roots of Pandanus amaryllifolius and synthesis of epi -pandamarilactonine-H

Article abstract of DOI:10.1021/np1003998

A new alkaloid (1a), named pandamarilactonine-H, which possesses a methyl-2-(pyrrolidin-2-yl)acetate function, was isolated from the roots of Pandanus amaryllifolius. Eleven known alkaloids were also isolated. Unambiguous assignment of the structure of 1a, including the absolute configuration, was accomplished by spectroscopic analysis and total synthesis of its enantiomer.

Full text of DOI:10.1021/np1003998

J. Nat. Prod. 2010, 73, 1453–1455
1453
Isolation of Pandamarilactonine-H from the Roots of Pandanus amaryllifolius and Synthesis of
epi-Pandamarilactonine-H
†
†
†
‡
,†
Mario A. Tan, Mariko Kitajima, Noriyuki Kogure, Maribel G. Nonato, and Hiromitsu Takayama*
Graduate School of Pharmaceutical Sciences, Chiba UniVersity, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan, and College of Science,
UniVersity of Santo Tomas, Espana, Manila 1015, Philippines
ReceiVed June 15, 2010
A new alkaloid (1a), named pandamarilactonine-H, which possesses a methyl-2-(pyrrolidin-2-yl)acetate function, was
isolated from the roots of Pandanus amaryllifolius. Eleven known alkaloids were also isolated. Unambiguous assignment
of the structure of 1a, including the absolute configuration, was accomplished by spectroscopic analysis and total synthesis
of its enantiomer.
The genus Pandanus comprises approximately 700 species that
are distributed in tropical and subtropical regions. Many species
1
of this genus are known for their medicinal properties. Phy-
tochemical studies on Pandanus species have identified essential
2
3
4
5,6
oils, lignans, ionones, benzofurans, terpenes, and alkaloids.
Pandanus amaryllifolius Roxb. (Pandanaceae), commonly known
as fragrant screw pine, is well studied owing to its importance in
folklore medicine and its structurally unique alkaloids. In our
continuing search for biologically active alkaloids from the genus
6
,7
Pandanus, the novel alkaloids from leaves of P. amaryllifolius
have encouraged us to investigate the alkaloidal constituents in the
roots.
Figure 1. 2D NMR correlations of 1a.
The crude alkaloid mixture obtained from a MeOH extract of
P. amaryllifolius roots was subjected to chromatographic separation
and yielded a new alkaloid (1a) and the known alkaloids pandama-
between the H-4 and H-6 olefinic methines, from the strong UV
absorption at 275 nm, and from the characteristic NMR signals
5a
5a
6a
6a
6b
6b
{δ
Hz, H-6), 1.99 (3H, d, J ) 0.9 Hz, H
C-3), 137.7 (C-4), 148.5 (C-5), 114.1 (C-6), 10.5 (C-17)}. The
H
6.98 (1H, dd, J ) 1.6, 0.9 Hz, H-4), 5.15 (1H, dd, J ) 8.0, 8.0
rilactones-1 and -32; pandamarilactonines-A, -B, -C, 6e-D,
6
f
6f
6f
6f
3
-17); δ 171.1 (C-2), 129.1
C
-
E, -F, -F-N-oxide, and -G; and dubiusamine-A. The
(
structure of 1a, named pandamarilactonine-H, was elucidated on
the basis of 1D and 2D NMR and HRMS spectroscopic data and
total synthesis. The known alkaloids were identified by comparing
their spectroscopic data with those reported in the literature.
1
1
H- H COSY spectrum of 1a showed that the three-carbon
methylene fragment (H -7/H -8/H -9) was connected to the olefinic
2
2
2
1
1
H-6 proton. In the lower segment of 1a, H- H COSY correlations
were observed from the remainder of the aliphatic methylenes and
methine to establish the fragment H
5. The chemical shifts of C-11 (δ
61.1) implied a neighboring nitrogen atom. Thus, a pyrrolidine
ring with an additional methylene attached to C-14 was constructed.
The remaining ester carbonyl (δ 172.8, C-16) and the OCH group
51.5) were attached to the C-15 methylene (δ 39.5).
Assignment of structure to the lower segment in 1a was validated
using HMBC analysis. The following correlations were observed:
-15 to C-13/C-14/C-16; H-14 to C-11; H -11 to C-12; H -13 to
C-11; and the OCH protons to C-16. The observed HMBC
correlation of H -9 to C-11 led to the gross structure of 1a as
indicated (Figure 1). The H and C NMR spectra (Supporting
Information) of 1a also showed minor peaks at δ 7.31, 5.60 and
113.4, 130.2, 133.7, which were attributed to the minor isomer
2
-11 to H
53.6) and the C-14 methine
2 2 2
-12/H -13/H-14/H -
1
(δ
C
C
C
3
(
δ
C
C
H
2
2
2
3
2
1
13
H
Pandamarilactonine-H (1a) was obtained as an amorphous solid
δ
C
24
and in optically active form, [R]
the molecular formula C16
spectrum (m/z 294.1689 [M + H] , calcd for C16
NMR spectra indicated the presence of aliphatic ester (δ
D
-43 (c 0.04, CHCl
3
). It had
1
(
1b) in a 3.6:1 (1a/1b) ratio, based on H NMR integration. The
observed upfield-shifted resonance of C-4 in 1b (δ 133.7)
compared to that of 1a (δ 137.7) was attributed to the γ-gauche
effect owing to the E configuration in the γ-alkylidene-γ-lactone
H
23NO , as revealed by the HRESIMS
4
+
C
H
24NO
4
, 294.1700).
172.8,
C
171.1, C-2) carbonyls, four sp olefinic
C
C
2
C-16) and lactone (δ
6
b
moiety. Although alkaloid 1a was isolated as a diastereomeric
mixture with 1b, we were able to synthesize them in the diaste-
reomerically and enantiomerically pure forms using D-proline as
the chiral starting material.
3
3
carbons, seven sp methylenes, one nitrogen-bearing sp methine
61.1, C-14), an allylic methyl (δ 10.5, C-17), and a methoxy
methyl (δ 51.5). A Z-configured γ-butylidene-R-methyl-R,ꢀ-
unsaturated lactone moiety was indicated by NOE correlation
(
δ
C
C
C
To obtain a definite structural assignment, including clarification
of the absolute configuration at C-14, the asymmetric total synthesis
of 1a was attempted. The synthetic strategy for formation of 1a
entailed condensation of γ-alkylidene butenolide (2) for the upper
segment with methyl pyrrolidinylacetate (3), which represents the
*
To whom correspondence should be addressed. Tel & Fax: +81-43-
2
90-2901. E-mail: htakayam@p.chiba-u.ac.jp.
†
Chiba University.
University of Santo Tomas.
‡
1
0.1021/np1003998  2010 American Chemical Society and American Society of Pharmacognosy
Published on Web 08/11/2010

1
454 Journal of Natural Products, 2010, Vol. 73, No. 8
Notes
a
Scheme 1
phy)], silica gel 60N [Kanto Chemical, 40-50 µm (for flash column
chromatography)], and Chromatorex NH (Fuji Silysia Chemical,
1
00-200 mesh) were used for column chromatography. Medium-
pressure liquid chromatography was carried out on a CPS-HS-221-05
silica gel prepacked column (Kusano Kagakukikai).
Plant Material. The whole plant of Pandanus amaryllifolius was
collected in Nueva Vizcaya, Philippines, in December 2008, and
identified by Assistant Professor Rosie Madulid, Department of
Biological Sciences, College of Science, University of Santo Tomas.
A voucher specimen (USTH-3728) was deposited in the Plant Sciences
Herbarium, Research Center for the Natural Sciences, University of
Santo Tomas.
Extraction and Isolation. The air-dried, ground roots (523 g) were
extracted exhaustively with MeOH (8.6 L) five times and filtered. The
combined filtrates were concentrated under reduced pressure to obtain
the MeOH extract (116 g). This was dissolved in 1 N HCl and extracted
three times with EtOAc. The aqueous layer was basified with Na
pH 7-8) and extracted exhaustively with 5% MeOH-CHCl . The
combined organic layers were dried with anhydrous MgSO and
2 3
CO
(
3
4
evaporated to obtain the crude base (2.1 g). A portion of the crude
base (2 g) was initially separated by silica gel flash column chroma-
a
Reagents and conditions: (a) ref 8, quant.; (b) ClCOOCH
, CH CN, 0 °C f rt, 6-19 h, 86%; (d)
N, sonication, 1 h, 83%; (e) H (balloon), 10% Pd/C,
MeOH, rt, 1 h, 78%; (f) Ag CO , CH CN, rt, 36 h, 57%.
2 3 3
CH , Et N, THF,
-
25 °C, 30 min, 71%; (c) TMSCHN
MeOH, C CO Ag, Et
2
3
tography using a CHCl
separated by silica gel flash column chromatography using 50% EtOAc/
hexane to yield pandamarilactone-1 (9.1 mg). The 2-5% MeOH/CHCl
eluate was separated by silica gel flash column chromatography using
a CHCl /EtOH gradient to give four fractions, A1-A4. Fractions A1,
3 3
/MeOH gradient. The CHCl eluate was
6
H
5
2
3
2
2
3
3
3
3
lower part of 1a. The synthesis of required compound 3 commenced
with the Cbz protection of D-proline (4) in quantitative yield. The
Cbz-protected-D-proline (5) was treated with ethyl chloroformate
and Et
A2, and A3 were separated by MPLC (60% EtOAc/hexane or 80%
EtOAc/hexane) to afford pandamarilactonine-A (9.9 mg), pandama-
rilactonine-B (9.6 mg), pandamarilactonine-C (1.1 mg), and pandama-
rilactonine-D (3.0 mg). A4 was separated by silica gel flash column
8
3
N in THF to afford mixed anhydride 6 in 71% yield. The
Arndt-Eistert reaction of 6 employing trimethylsilyldiazomethane
3
chromatography (EtOAc f 2% EtOH/CHCl ) to give subfractions
9
(TMSCHN
2
) in CH
3
CN gave the desired R-diazoketone (7) in 86%
B1-B5 and pure pandamarilactone-32 (14.1 mg). Subfraction B1 was
purified by amino-silica gel chromatography (50% EtOAc/hexane) to
obtain pandamarilactonine-E (4.4 mg). Subfraction B3 was separated
by amino-silica gel chromatography (40% EtOAc/hexane) to afford
pandamarilactonine-H (1a, 3.0 mg). Subfraction B4 was purified by
amino-silica gel chromatography to afford pandamarilactonine-G (1.7
mg). Subfraction B5 was purified by amino-silica gel chromatography
yield. Compound 7 was then subjected to a key homologation
reaction step using the Wolff rearrangement. In this process, 7 was
initially suspended in MeOH. Then, a solution of silver benzoate
in Et
3
N was gradually added under sonication. This gave Cbz-
9a
protected methyl pyrrolidinylacetate (8) as a colorless oil in 83%
yield. The formation of methyl pyrrolidinylacetate
9
a,10
(3) in 78%
to afford pandamarilactonine-F (1.3 mg). The 5-10% MeOH/CHCl
3
yield was accomplished by hydrogenolysis of 8 in 10% Pd/C and
MeOH. Condensation of 3 with a 3:2 (Z/E) mixture of γ-alkylidene
eluate was separated by amino-silica gel chromatography using an
EtOAc/hexane gradient to obtain pandamarilactonine-F (2.3 mg),
pandamarilactone-32 (1.2 mg), and mixtures of pandamarilactonines-A
6
b,7b
butenolide
2 3 3
(2) utilizing Ag CO in CH CN afforded the
and -B. The 20-50% MeOH/CHCl
3
eluate was separated by
gradient to
alkaloidal adducts in 57% combined yield. Careful chromatographic
separation furnished synthetically pure epi-pandamarilactonine-H
amino-silica gel chromatography using an EtOH/CHCl
3
2
1
afford dubiusamine-A (44.8 mg). The 50% MeOH/CHCl
3
f MeOH
(
9a) {[R]
D
3
+62 (c 0.07, CHCl )}, having a Z configuration, as
eluate was separated by amino-silica gel (10% EtOH/CHCl
3
) and silica
the major compound, and the synthetically pure compound 9b
3
gel (20% MeOH/CHCl ) open column chromatography to afford
22
diastereomer {[R]
D
3
+67 (c 0.05, CHCl )}. Both of the synthesized
pandamarilactonine-F-N-oxide (1.2 mg).
compounds 9a and 9b had a C-14R configuration. The spectral data
24
Pandamarilactonine-H (1a): amorphous solid; [R]
D
-43 (c 0.04,
1
1
13
(
H and C NMR, HRMS) and chromatographic behavior of 9a
3
CHCl ); UV (MeOH) λmax (log ε) 201 (1.83), 275 (2.45) nm; H NMR
are in excellent agreement with those of the major peaks in the
natural product (1a), except for the opposite sign of the optical
rotation. On the basis of these findings, the absolute configuration
of pandamarilactonine-H was elucidated to be C-14S, and its
structure was conclusively determined as shown in 1a. Furthermore,
the structure of 1b was also determined by comparing the minor
(CDCl , 400 MHz) δ 6.98 (1H, dd, J ) 1.6, 0.9 Hz, H-4), 5.15 (1H,
3
dd, J ) 8.0, 8.0 Hz, H-6), 3.67 (3H, s, -OCH
2.72 (3H, overlapped, H -9, H-14), 2.60 (1H, dd, J ) 14.8, 4.0 Hz,
H-15a), 2.40 (2H, m, H -7), 2.24 (1H, m, H-15b), 2.15 (1H, m, H-11b),
.02 (1H, m, H-13a), 1.99 (3H, d, J ) 0.9 Hz, H -17), 1.74 (2H, m,
3
), 3.12 (1H, m, H-11a),
2
2
2
3
1
3
2 2 3
H -12), 1.64 (2H, m, H -8), 1.55 (1H, m, H-13b); C NMR (CDCl ,
1
1
5
25 MHz) δ 172.8 (CdO, C-16), 171.1 (CdO, C-2), 148.5 (C, C-5),
1
signals observed in the H NMR spectrum of the natural product
37.7 (CH, C-4), 129.1 (C, C-3), 114.1 (CH, C-6), 61.1 (CH, C-14),
with those of 9b. Pandamarilactonine-H (1a) is the first Pandanus
alkaloid having a methyl-2-(pyrrolidin-2-yl)acetate moiety.
Compounds 1a, 9a, 9b, and dubiusamine-B were evaluated for
their toxicity on human tumor cell lines A549, HT29, and HCT116.
No cytotoxicity was detected for the four compounds (IC50 values
3.9 (CH
2
, C-9), 53.6 (CH
2
, C-11), 51.5 (CH
3
, -OCH
3
), 39.5 (CH
2
,
,
C-15), 30.8 (CH
2
, C-13), 28.3 (CH
2
, C-8), 24.2 (CH
2
, C-7), 22.3 (CH
2
+
C-12), 10.5 (CH , C-17); HRESIMS m/z 294.1689 [M + H] , calcd
for C16
3
4
H24NO , 294.1700.
1
Minor Isomer (1b): H NMR (CDCl
3
, 400 MHz) δ 7.31 (H-4),
3
, 125 MHz) δ 133.7 (C-4), 130.2 (C-3),
1
3
5
1
.60 (H-6); C NMR (CDCl
13.4 (C-6).
>
5 µg/mL).
Preparation of Mixed Anhydride 6. To a stirred solution of 5 (100
mg, 0.402 mmol) in THF (2.0 mL) in an ice-salt bath were added
Et N (56 µL, 0.402 mmol, 1.0 equiv) and ClCOOCH CH (38 µL, 0.402
mmol, 1.0 equiv) sequentially. The reaction mixture was stirred
mechanically for 30 min and quenched with saturated NH Cl. The
resulting aqueous layer was extracted three times with CHCl . The
combined organic layers were dried over MgSO and concentrated under
Experimental Section
General Experimental Procedures. Optical rotations were measured
on a JASCO P-1020 polarimeter. UV spectra were recorded on a
JASCO V-560 UV-vis spectrophotometer. HRESIMS were recorded
on a Thermo Fisher Scientific Exactive or a JEOL AccuTOF-T100LP
spectrometer. NMR spectra were recorded on a JEOL JNM A-500, a
JEOL JNM A-400, or a JEOL JNM ECP400 spectrometer. The
chemical shifts are given in δ (ppm) and coupling constants, in Hz.
Kieselgel 60 [Merck, 70-230 mesh (for open column chromatogra-
3
2
3
4
3
4
reduced pressure. Title compound 6 was obtained after silica gel flash
column chromatography (50% EtOAc/hexane) in 71% yield as a
25
1
colorless oil (91.6 mg): [R]
D
3
+52 (c 0.19, CHCl ); H NMR (DMSO-

Notes
Journal of Natural Products, 2010, Vol. 73, No. 8 1455
d
6
, VT 100, 400 MHz) δ 7.34-7.29 (5H, m, Ph of Cbz), 5.07 (2H, s,
CH of Cbz), 4.23 (1H, m, H-2), 3.46 (4H, overlapped, H -5,
-4), 1.08 (3H, t, J ) 7.0 Hz,
100 MHz) 167.1 (C,
CO CO -),
(1H, m, H-11b), 2.02 (3H, br s, H
(2H, m, H -12), 1.65 (2H, m, H -8), 1.55 (1H, m, H-13b); C NMR
(CDCl , 100 MHz) δ 172.1 (CdO, C-16), 171.0 (CdO, C-2), 148.8
(C, C-5), 133.8 (CH, C-4), 130.0 (C, C-3), 113.4 (CH, C-6), 61.1 (CH,
C-14), 53.5 (CH , C-9), 53.4 (CH , C-11), 51.5 (CH ), 39.5
, C-15), 30.8 (CH , C-13), 28.7 (CH , C-8), 24.2 (CH , C-7), 22.3
, C-12), 10.8 (CH , C-17); HRESIMS m/z 294.1721 [M + H] ,
, 294.1705.
3
-17), 2.01 (1H, m, H-13a), 1.75
1
3
2
2
2
2
-
-
-
OCH
OCH
CH
2
CH
3
), 1.83-2.12 (4H, m, H
3
2
-3, H
2
3
1
3
2
CH
);
C
NMR (CDCl
3
,
δ
2
CO
2
CO
2
-), 154.0 (CdO of Cbz), 148.6 (C, -CH
2
2
2
2
2
3
, -OCH
3
1
-
3
36.2 (C), 127.8 (CH), 127.9 (CH), 128.4 (CH) [Ph of Cbz], 67.3 (CH
CO CH CH ), 65.9 (CH of Cbz), 58.7 (CH, C-2), 46.9 (CH , C-5),
0.5 (CH , C-3), 23.4 (CH , C-4), 13.9 (CH , -CO CH CH ); HRES-
IMS m/z 344.1115 [M + Na] , calcd for C16 Na, 344.1110.
Preparation of r-Diazoketone (7). To a stirred solution of 6 (68
mg, 0.212 mmol) in CH CN (610 µL) at 0 °C was added TMSCHN
2.0 M in hexane, 210 µL, 0.424 mmol, 2.0 equiv). The reaction mixture
was stirred mechanically for 6 h at 0 °C and for an additional 19 h at
rt. The reaction mixture was quenched with Et O and washed
successively with saturated NaHCO and brine. The organic layer was
dried over MgSO and concentrated under reduced pressure. Purification
2
,
(CH
(CH
2
2
2
2
+
2
2
3
2
2
2
3
2
2
3
2
2
3
calcd for C16H24NO
4
+
H
19NO
6
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research from the Japan Society for the Promotion of Science.
3
2
(
Supporting Information Available: H and 13C NMR spectra of
pandamarilactonine-H (1a), epi-pandamarilactonine-H (9a), and com-
pound 9b, and structures of pandamarilactonines-A to -G. This material
is available free of charge via the Internet at http://pubs.acs.org.
1
2
3
4
by flash column chromatography (50% EtOAc/hexane) afforded
compound 7 as a colorless oil in 86% yield (50 mg). The spectral data
of R-diazoketone (7) were in excellent agreement with those in the
References and Notes
(
1) Quisumbing, E. Medicinal Plants of the Philippines; Bureau of
Printing: Manila, 1978.
9
literature.
(
2) (a) Macleod, A. J.; Pieris, N. M. Phytochemistry 1982, 21, 1653–
Preparation of Cbz-Protected Methyl Pyrrolidinylacetate (8). To
a solution of 7 (45 mg, 0.162 mmol) in MeOH (1.6 mL) was added a
1
657. (b) Vahirua-Lechat, I.; Menut, C.; Roig, B.; Bessiere, J. M.;
Lamaty, G. Phytochemistry 1996, 43, 1277–1279.
solution of silver benzoate (C
6
H
5
CO
2
Ag, 7.4 mg, 0.0324 mmol, 0.2
(3) (a) Takayama, H.; Kuwajima, T.; Kitajima, M.; Nonato, M. G.; Aimi,
N. Nat. Med. 1999, 53, 335–336. (b) Jong, T.; Chau, S. W.
Phytochemistry 1998, 49, 2145–2148.
equiv) in Et N (90 µL, 4 equiv, 0.648 mmol) under sonication. The
3
reaction mixture was sonicated for 1 h, and the MeOH was evaporated
under reduced pressure. EtOAc was added, and the resulting organic
(
4) (a) Inada, A.; Ikeda, Y.; Murata, H.; Inatomi, Y.; Nakanishi, T.;
Bhattacharyya, K.; Kar, T.; Bocelli, G.; Cantoni, A. Phytochemistry
solution was successively washed with saturated NaHCO
dried over MgSO , and concentrated under reduced pressure. Purifica-
3
and brine,
2
005, 66, 2729–2733. (b) Tan, M. A.; Takayama, H.; Aimi, N.;
Kitajima, M.; Franzblau, S. G.; Nonato, M. G. J. Nat. Med. 2008, 62,
32–235.
4
tion by silica gel flash column chromatography (50% EtOAc/hexane)
afforded compound 8 in 83% yield as a colorless oil (37 mg). The
spectral data of Cbz-protected methyl pyrrolidinylacetate were in
2
(
5) (a) Nonato, M. G.; Garson, M. J.; Truscott, R. J.; Carver, J. A.
Phytochemistry 1993, 34, 1159–1163. (b) Sjaifullah, A.; Garson, M. J.
ACGC Chem. Res. Commun. 1996, 5, 24–27. (c) Salim, A. A.; Garson,
M. J.; Craik, D. J. J. Nat. Prod. 2004, 67, 54–57.
9
a
excellent agreement with those in the literature.
Preparation of Methyl Pyrrolidinylacetate (3). To a stirred mixture
of 8 (45 mg, 0.162 mmol) in MeOH (3.0 mL) was added 10% Pd/C
(6) (a) Takayama, H.; Ichikawa, T.; Kuwajima, T.; Kitajima, M.; Seki,
H.; Aimi, N.; Nonato, M. G. J. Am. Chem. Soc. 2000, 122, 8635–
(
11 mg). The resulting mixture was stirred mechanically under a
8
639. (b) Takayama, H.; Ichikawa, T.; Kitajima, M.; Nonato, M. G.;
hydrogen atmosphere (balloon) at rt for 1 h, and the heterogeneous
mixture was filtered through a pad of Celite (EtOAc). The filtrate was
concentrated under reduced pressure to obtain methyl pyrrolidinylacetate
Aimi, N. Chem. Pharm. Bull. 2002, 50, 1303–1304. (c) Takayama,
H.; Ichikawa, T.; Kitajima, M.; Nonato, M. G.; Aimi, N. J. Nat. Prod.
2
001, 64, 1224–1225. (d) Takayama, H.; Ichikawa, T.; Kitajima, M.;
9
a,10
(
3),
Synthesis of 9a and 9b. To a stirred mixture of γ-alkylidene
butenolide (2, 40 mg, 0.147 mmol, 1.4 equiv) and 3 (15 mg, 0.105
mmol) in CH CN (1.0 mL) was added Ag CO (50 wt % on Celite, 87
mg, 0.158 mmol, 1.5 equiv). The reaction mixture was stirred at rt for
6 h. The heterogeneous mixture was filtered through a Celite pad,
and the filtrate was concentrated under reduced pressure. Purification
using MPLC (2% EtOH/CHCl ) afforded compounds 9a (32%) and
which was used in the next step without further purification.
Aimi, N.; Lopez, D.; Nonato, M. G. Tetrahedron Lett. 2001, 42, 2995–
2996. (e) Tan, M. A.; Kitajima, M.; Kogure, N.; Nonato, M. G.;
Takayama, H. Tetrahedron 2010, 66, 3353–3359. (f) Tan, M. A.;
Kitajima, M.; Kogure, N.; Nonato, M. G.; Takayama, H. Tetrahedron
Lett. 2010, 51, 4143–4146.
3
2
3
(
7) (a) Nonato, M. G.; Takayama, H.; Garson, M. J. In The Alkaloids;
Cordell, G. A., Ed.; Academic Press: New York, 2008; Vol. 66,
Chapter 4, pp 215-249. (b) Takayama, H.; Sudo, R.; Kitajima, M.
Tetrahedron Lett. 2005, 46, 5795–5795. (c) Takayama, H.; Kuwajima,
T.; Kitajima, M.; Nonato, M. G.; Aimi, N. Heterocycles 1999, 50,
3
3
9
b (25%) as colorless oils.
2
1
epi-Pandamarilactonine-H (9a): colorless oil; [R]
D
+62 (c 0.07,
7
5–78.
1
13
CHCl
3
); H and C NMR data were identical to those of the natural
(8) Corey, E. J.; Shibata, S.; Bakshi, R. K. J. Org. Chem. 1988, 53, 2861–
2863.
+
4
product 1a; HRESIMS m/z 294.1729 [M + H] , calcd for C16H24NO ,
2
94.1705.
Compound 9b: colorless oil; [R]
(9) (a) Cassal, J. M.; F u¨ rst, A.; Meier, W. HelV. Chim. Acta 1976, 59,
2
2
1
1918–1923. (b) Bure sˇ , F.; Ji rˇ ´ı , K. Tetrahedron: Asymmetry 2005, 16,
D
3
+67 (c 0.05, CHCl ); H NMR
1
347–1354.
10) Hashimoto, N.; Funatomi, T.; Misaki, T.; Tanabe, Y. Tetrahedron
006, 62, 2214–2223.
(
CDCl
3
, 400 MHz) δ 7.30 (1H, d, J ) 0.8 Hz, H-4), 5.62 (1H, dd, J
(
)
3
8.6, 8.6 Hz, H-6), 3.67 (3H, s, -OCH ), 3.09 (1H, m, H-11a), 2.72
2
(
2H, overlapped, H-9a, H-14), 2.56 (1H, dd, J ) 14.8, 4.0 Hz, H-15a),
2
.37 (1H, m, H-7a), 2.26 (3H, overlapped, H-7b, H-9b, H-15b), 2.15
NP1003998