Iseluxine: A Novel Isoquinolinone Alkaloid from Isei a luxurians §

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N o te s 1023

Iseluxine: A Novel Isoquinolinone Alkaloid from Isei a luxurians §

Thomas Schimming3, Kristina Jenett-Siem s3, Karsten Siemsb, Ludger W ittec, M ahabir P. G uptad and Eckart Eich3 *

a Institut für Pharm azie (P harm azeutische B iologie), Freie U niversität B erlin, B erlin, G erm any.

Fax: ++49 (0) 30 838 53729.

E-mail: eckeich@ zedat.fu-berlin.de

b A nalytiC on AG, N L Potsdam , H erm an n sw erd er H aus 17, D-14473 Potsdam , G erm an y

c In stitu t für Pharm azeutische Biologie, Technische U niversität B raunschw eig, G erm an y

d C en tro de Investigaciones F arm acognösticas de la Flora P an am en a (C IF L O R P A N ), F aeultad de Farm acia, U niversidad de P anam a, R epublic of P anam a

* A u th o r for corresp o n d en ce and re p rin t req u ests Z. N aturforsch. 55c, 1023-1025 (2000);

received A ugust 3, 2000

Iseia luxurians (M oric.) O ’D o n e ll, Isoqu in o lin o n e A lkaloids, C onvolvulaceae

A novel isoquinolinone alkaloid, iseluxine (1), has been isolated from th e epigeal p arts of Iseia luxurians (M oric.) O ’D o n e l l (C onvolvulaceae), a clim ber indige

nous to the tropical A m ericas. S tru ctu ral elucidation was achieved by H RM S, 'H N M R , 13C N M R , and H M B C spectroscopy. N- and / o r O -m ethyl derivatives o f 1 are already know n from certain M agnoliidae families, e.g., the F um ariaceae, the L auraceae, o r the P ap averaceae.

Iseluxine, the “ missing lin k ” in the biosynthesis o f these m ethyl derivatives from dopam ine, is the first iso q u in o li

none alkaloid characterized by a catechol substructure.

Introduction

Iseia luxurians ( Mo r i c.) O ’Do n e l l is a herba

ceous climber mostly distributed along river and stream margins. The monotypic Am erican genus Iseia occurs from H onduras south to the northern part of Argentina (Austin, 1975) and belongs to the Cresseae tribe of the Convolvulaceae. The plants subjected to our study were cultivated in a tropical greenhouse from seeds collected in the wild, and have been harvested at the stage of 1 2

§ P art 12 in the series “ Phytochem istry and C hem otax- onom y of the C onvolvulaceae” . F or p a rt 11 see Tofern et al. - P resented, in p art, at the 46th A n n u al C ongress of the Society for M edicinal P lan t R esearch, A ugust, 31 - S eptem ber, 4, 1998, V ienna, A ustria.

months. The alkaloid has finally been obtained from the aqueous phase of the plant extract.

Only small information is provided by the litera

ture concerning the phytochemistry of I. luxurians.

A GC-MS study of numerous convolvulaceous species revealed calystegines Bj and B2, hydrophi

lic nortropane alkaloids commonly distributed in Convolvulaceae and Solanaceae, to be present also in the leaves and the seeds of this plant (Schimming et al., 1998).

M aterials and Methods Plant material

Iseia luxurians ( Mo r i c.) O ’Do n e l l, Convolvula

ceae (voucher specimen Panam a 1/1995, Nr. 25; In

stitut für Pharmazie, Pharmazeutische Biologie, Freie Universität Berlin). The seeds were collected on the banks of the Panama Canal, near Gamboa, Republic of Panama, in 1995.

Extraction and isolation

D ried ground aerial parts of Iseia luxurians (50 g), harvested from a tropical greenhouse (B er

lin) at the age of 1 2 months, were extracted with 600 ml M eOH (70%). A fter evaporation, the ex

tract was acidified (2% aq. tartaric acid) and parti

tioned between H 20 and organic solvents (petrol, C H2C12, EtOAc). The aq. phase was then made alkaline (10% aq. N H 3) and extracted with C H C l3-i-PrOH (3:1; v/v). The remaining aq. phase was again reduced to 50 ml in vacuo, sim ulta

neously removing N H3 from the solution. Further purification was achieved by column chrom atogra

phy (LiChroprep R P-8, 40 -6 3 |im, Merck Art.

9362) [H20 , H20 -M e 0 H mixtures, fractions 1 - 12]. Fractions 9 -1 0 , eluting with H20 -M e 0 H (80:20; v/v), reduced to 1 ml, were subm itted to preparative HPLC (LiChrosorb RP 18, 7 |im m aterial) [H20 -M e 0 H (85:15; v/v)] at 4.5 ml/min.

Iseluxine (3,4-dihydro-6,7-dihydroxy-l(2//)- isoquinolinone): EI-MS (70 eV, 240°), m /z (rel.

int.): 179 [M]+ (75), 150 (100), 122 (83); HR-MS, m/z: 179.0584 (C9H9N 0 3+., calc. 179.0582); lH N M R (400 MHz, CD3OD): d 2.80 (2H, t, 7=6.5 Hz, H-4), 3.43 (2H, t, 7=6.5 Hz, H-3), 6.65 (1H, s, H-5), 7.34 (1H, s, H -8); reaction with 2,6-dichlor-

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1024 N o te s

oquinone-4-chloroim ide / N H3 (Gibbs reagent) on the TLC (silica gel, CHCl3-M eOH, 4:1, detection UV 254 nm, R f 0.45).

Results and Discussion

Structural elucidation of 1 (Table I) was achieved by EI-MS, HR-MS, *H NMR, 13C NMR, and HM BC spectroscopy. The *H NM R showed two arom atic s hinting to a 1,2,4,5-tetrasubstituted arom atic system (d 6.65, 1H, H-5; d 7.34, 1H, H-

8) and two t (d 2.80, 7=6.5 Hz, H-4; d 3.43, 7=6.5 Hz, H-3) for two protons, each. From the HR-MS, the molecular formula could be deduced as C9H9N O3. HM BC measurem ents finally allowed total structural assignments (Table II). Thus, the isolated com pound has to be 3,4-dihydro-6,7-dihy- Table I.

C om p o u n d s R i R2 R3

Iseluxine (1) H H H

N orthalifoline H c h3 h

T halifoline C H , c h3 h

C orydaldine H c h3 c h3

N o roxyhydrastinine H -c h2 -

O xyhydrastinine c h3 - c h2 -

N -M ethylcorydaldine c h3 c h3 c h3

Table II.

C 13C N M R H M B C -correlation

(100 M H z, D M S O -d6)

C - l 165.1 (s) H-8

C-3 39.2 (t)

C-4 26.7 (t)

C-4a 121.0 (s) H-4, H-5

C-5 113.9 (d)

C-6 148.0 (s)* H-5, H-8

C-7 143.7 (s)* H -5, H-8

C-8 114.0 (d)

C-8a 131.7 (s) H-4, H-8

* Interch an g eab le.

d roxy-l(2//)-isoquinolinone, which, as a novel al

kaloid, we nam ed iseluxine. Its structure is charac

terized by a catechol moiety, and obviously, dopam ine can be regarded as its biogenetic pre

cursor.

Remarkably, this is the first report on an isoquinolinone alkaloid from the Convolvulaceae and even from the Solanales. The occurrence of isoquinolinones such as corydaldine, oxyhydrastinine, thalifoline, and their derivatives in certain families of the M agnoliopsida sensu stricto (Frohne and Jensen, 1998) (A nnonaceae, Berberidaceae, Fu- mariaceae, H ernandiaceae, Lauraceae, Papavera- ceae, R anunculaceae) is well docum ented (Krane and Shamma, 1982; Shamma et al., 1974; Cava and Bessho, 1966; Hussain et al., 1983; Doskotch et al., 1969; Chou et al., 1994). However, there are only two reports on isoquinolinone alkaloids from the Rosopsida: N-m ethylcorydaldine (also described as 6,7-dimethoxyhydrastine) has been isolated from Hammada articulata ^{( M}o q u i n) Il j i n ssp. sco- paria Po m e l, a chenopodiaceous plant indigenous to the Middle East (B enkrief et al., 1990), and from Evodia daniellii ^Be n t h. (R utaceae), a plant endemic to Korea (M itsunaga et al., 1991).

It should be m entioned that 1 seems to occur in the growth period up to about 1 2 months only, since it is not detectable in later stages of develop

ment. The potential occurrence of m ethylated de

rivatives, e.g., corydaldine, has been investigated by GS-MS m easurem ents of all lipophilic fractions of the plant (petrol, methylene chloride, ethyl ace

tate), but definitely no isoquinolinones could be detected.

Acknowledgements

The authors are indebted to Mrs. E. Bäumel- Eich (Berlin) and to Mr. A. F. Espinosa (Facultad de Farmacia, Universidad de Panam a) for essen

tial support in exploring and collecting the plant material. We thank Mrs. U. Ostwald (Institut für Chemie, FU Berlin) and Dr. J. Jakupovic (Analyti- Con AG Potsdam ) for HR-MS and HM BC m ea

surements. Finally, skilfull technical assistance by Mrs. J. Schulz (Institut für Pharmazie, FU Berlin) is gratefully acknowledged.

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N o te s 1025

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