Spermidine Alkaloidal Glycosides from Meehania
Journal of Natural Products, 2009, Vol. 72, No. 6 1055
2
0
Meehanine A (1): colorless, amorphous powder; [R] -4.2 (c 0.26,
D
MeOH); CD (c 0.050, MeOH) λ(θ) 247 (4000), 226 (-30 100), 203
1
13
(
8
32 000) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
+
46.4029 [M + H] (calcd for C42
Meehanine B (2): colorless, amorphous powder; [R]
MeOH); CD (c 0.052, MeOH) λ(θ) 246 (3300), 222 (-14 700), 202
60 3
H N O15, 846.4026).
2
0
D
-9.2 (c 0.37,
1
13
(
8
2300) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
+
04.3929 [M + H] (calcd for C40
Meehanine C (3): colorless, amorphous powder; [R]
MeOH); CD (c 0.060, MeOH) λ(θ) 252 (2600), 224 (-72 300), 205
58 3
H N O14, 804.3920).
20
D
-8.1 (c 0.12,
1
13
(
7
65 200) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
+
42.3761 [M + H] (calcd for C35
Meehanine D (4): colorless, amorphous powder; [R]
MeOH); CD (c 0.093, MeOH) λ(θ) 234 (4100), 203 (-2500) nm; H
56 3
H N O14, 742.3764).
22
D
-12.9 (c 0.31,
1
1
3
NMR and C NMR, Tables 1 and 2; HRFABMS m/z 864.3541 [M -
-
H] (calcd for C44
Meehanine E (5): colorless, amorphous powder; [R]
MeOH); CD (c 0.072, MeOH) λ(θ) 247 (2000), 224 (-29 300), 203
54 3
H N O15, 864.3556).
Figure 3. Structures of 1a-1d.
2
3
D
-10.8 (c 0.72,
1
13
dissolved in 7% HCl (1 mL) and stirred for 1 h at 60 °C. After cooling,
the solution was partitioned between CHCl (3 mL) twice. From the
3
CHCl layer, 2-methylbutyric acid was obtained. From the 7% HCl
3
layer, 1a (2.4 mg) was obtained as described for 1. Compound 1a (2.0
(
8
15400) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
+
32.3871 [M + H] (calcd for C41
Meehanine F (6): colorless, amorphous powder; [R]
MeOH); CD (c 0.052, MeOH) λ(θ) 238 (4000), 222 (-13 500), 203
58 3
H N O15, 832.3869).
22
D
-7.1 (c 1.04,
mg) was dissolved in 7% HCl (1 mL) and stirred for 3 h at 90 °C.
1
13
(
8
7400) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
Then, the solution was extracted with CH
layer from 8 and the CH Cl
dried over 3 Å molecular sieves. To the solutions were added
-hydroxybenzotriazole monohydrate, N,N′-dicyclohexylcarbodiimide,
Cl
2 2
(3 mL) twice. The CHCl
3
-
30.3710 [M - H] (calcd for C41
Meehanine G (7): colorless, amorphous powder; [R]
MeOH); CD (c 0.057, MeOH) λ(θ) 242 (3700), 220 (-12 900), 201
56 3
H N O15, 830.3713).
2
2
layer from 1a were washed with H
2
O and
21
D
-8.4 (c 0.57,
1
1
13
(
8
4600) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
and (S)-1-(1-naphthyl)ethylamine (10 mg each). After the mixtures had
been stirred for 3 h at room temperature, filtration and concentration
gave residues, which were purified by a silica gel column [Wakogel
C-200, Wako Pure Chemical Industry, Ltd., 20 × 20 mm, eluted with
hexane, hexane-EtOAc (9:1, 8:2, 5:5) and EtOAc]. The 8:2 fractions
were analyzed by HPLC and detected at 280 nm. Analytical HPLC
was performed on a Cosmosil 5C18-AR-II column (4.6 × 250 mm) at
+
18.3711 [M + H] (calcd for C40
Meehanine H (8): colorless, amorphous powder; [R]
MeOH); CD (c 0.049, MeOH) λ(θ) 247 (3900), 222 (-27 00), 204
56 3
H N O15, 818.3713).
20
D
-1.0 (c 0.31,
1
13
(
8
22 200) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
-
24.4157 [M - H] (calcd for C40
Meehanine I (9): colorless, amorphous powder; [R]
MeOH); CD (c 0.030, MeOH) λ(θ) 248 (6200), 223 (-20 500), 200
62 3
H N O15, 824.4183).
2
2
D
-7.3 (c 0.30,
2
0 °C using acetonitrile-water (40:60) as the solvent. Peaks were
1
13
(
7
10 100) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
detected with a Tosoh UV8010 UV detector. (S)-2-Methyl-N-[(S)-1-
1-naphthyl)ethyl]butyramide (t 36.1 min) was identified as the product
+
84.4236 [M + H] (calcd for C38
Meehanine J (10): colorless, amorphous powder; [R]
MeOH); CD (c 0.040, MeOH) λ(θ) 255 (3800), 222 (-27 600), 203
62 3
H N O14, 784.4234).
(
R
20
D
-6.8 (c 0.41,
resulting from the 2-methylbutyryl moiety of 1a and 8 by comparing
their retention times with those of the authentic samples, (S)-2-methyl-
1
13
(
8
27 600) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
N-[(S)-1-(1-naphthyl)ethyl]butyramide (t
N-[(S)-1-(1-naphthyl)ethyl]butyramide (t
R
36.1 min) and (R)-2-methyl-
37.7 min).
+
24.4208 [M + H] (calcd for C40
Meehanine K (11): colorless, amorphous powder; [R]
MeOH); CD (c 0.042, MeOH) λ(θ) 253 (4700), 223 (-22 400), 205
H
62
N
3
O
15, 824.4183).
20,21
R
21
D
-6.9 (c 0.32,
Sugar Identification. Each compound [1-11 (1.0 mg)] was refluxed
with 7% HCl (1 mL) for 2 h. After cooling, the reaction mixture was
passed through an Amberlite IRA400 column, and the eluate was
concentrated. The residues were dissolved in pyridine (0.5 mL) and
stirred with L-cysteine methyl ester (5 mg) for 1.5 h at 60 °C, and then
1
13
(
8
23 900) nm; H NMR and C NMR, Tables 1 and 2; HRFABMS m/z
+
12.4175 [M + H] (calcd for C39
Acid Hydrolysis of 1 and N-Acetylation of Aglycone (1a).
Compound 1 (45 mg) was dissolved in 7% HCl (2 mL) and stirred for
h at 60 °C. After cooling, the reaction mixture was passed through
62 3
H N O15, 812.4183).
ꢁ
-tolyl isothiocyanate (20 µL) was added to the mixture and heated at
0 °C for 1.5 h. The reaction mixtures were analyzed by HPLC and
detected at 250 nm. Analytical HPLC was performed on a Shiseido
Capcell Pak C18 column (4.6 × 250 mm) at 20 °C using CH CN-0.2%
TFA in H O (25:75) as the solvent. Peaks were detected with a Tosoh
UV8010 UV detector. D-Glucose (t 18.5 min) and L-rhamnose (t 29.7
1
6
an Amberlite IRA400 column, and the eluate was concentrated. The
residue was subjected to preparative HPLC [column, Kanto Chemical,
Mightysil RP-18 GP, 10 × 250 mm; solvent, methanol-water (20:
3
2
80); detector, UV 210 nm] to yield compound 1a (15.4 mg). Compound
R
R
1
a (12.7 mg) was dissolved in saturated sodium bicarbonate solution
min) were identified as the sugar moieties of 1-11 by comparing their
retention times with those of the authentic samples of D-glucose (t
18.5 min), L-glucose (tR 17.0 min), L-rhamnose (tR 29.7 min), and
R
(
2 mL) and stirred with acetic anhydride (120 µL) for 1 h at 0 °C. The
reaction mixture was passed through a Diaion HP-20 column (20 ×
0 mm), and the 90% MeOH eluate was concentrated. The residue
was subjected to preparative HPLC [column, YMC, ODS-AM, 10 ×
0 mm; solvent, acetonitrile-water (30:70); detector, UV 210 nm] to
yield compound 1b (5.0 mg). Compound 1a: colorless, amorphous
R
7
D-rhamnose (using D-cysteine methyl ester and L-rhamnose, t 15.3
1
7
min).
3
Acknowledgment. We thank Mr. S. Sato and Mr. T. Matsuki, of
Tohoku Pharmaceutical University, for assisting with the MS measure-
ments and Mr. H. Hayasaka and K. Ohba of the Department of
Experimental Station for Medicinal Plant Studies, Tohoku University,
for supplying the plant material.
2
2
powder; [R]
D
-18.1 (c 0.53, MeOH); CD (c 0.028, MeOH) λ(θ) 249
1
13
(
4
1021), 227 (-31 500), 202 (10396) nm; H NMR and C NMR, Table
+
+
; FABMS m/z 392 [M + H] , 414 [M + Na] . Compound 1b:
1
colorless, amorphous powder; H NMR, Table 4; EIMS m/z 433 (17)
+
+
+
[
5
M] , 415 (10) [M - H
7 (92), 43 (74).
MTPA Ester of 1b. To a solution of 1b (2 mg each) in pyridine
2
O] , 390 (29) [M - Ac] , 233 (31), 147 (100),
Supporting Information Available: NMR spectra, tables of HMBC
data for compounds 1-11 and 1a, and the NOE data of 1 and 1a. This
material is available free of charge via the Internet at http://pubs.acs.org.
(
(
100 µL) was added (R)-(-)-MTPA chloride or (S)-(+)-MTPA chloride
2 µL), and the mixture was stirred for 1 h at 0 °C. The solvent was
subjected to preparative HPLC [column, YMC, ODS-AM, 10 × 300
mm; solvent, methanol-water (7:3); detector UV, 210 nm] to give the
8
References and Notes
(
(
1) Ganem, B. Acc. Chem. Res. 1982, 15, 290–298.
-O-(S)-(-)-MTPA ester of 1b (1c, 1 mg, FABMS: m/z 650 [M +
2) Frydman, B.; Bhattacharya, S.; Sarkar, A.; Drandarov, K.; Chesnov,
S.; Guggisberg, A.; Popaj, K.; Sergeyev, S.; Yurdakul, A.; Hesse, M.;
Basu, H. S.; Marton, L. J. J. Med. Chem. 2004, 47, 1051–1059.
3) Ovenden, S. P. B.; Cao, S.; Leong, C.; Flotow, H.; Gupta, M. P.;
Buss, A. D.; Butler, M. S. Phytochemistry 2002, 60, 175–177.
+
H] ) and the 8-O-(R)-(+)-MTPA ester of 1b (1d, 1 mg, FABMS: m/z
-
1
6
48 [M - H] ) as colorless, amorphous powders. H NMR: Table 4.
Acid Hydrolysis of 8 and 1a and Determination of the Stereo-
(
chemistry of 2-Methylbutyric Acid. Compound 8 (10 mg) was