Carapanaubine: An oxindole alkaloid from Bleekeria vitiensis

Phytochemwry, 1974.Vol 13.pp.50310504 Pcrgamon Press.

Prmted m England.

CARAPANAUBINE: AN OXINDOLE ALKALOID BLEEKERIA VITIENSIS” SHAIDA School of Chemistry

KANJI

and Chemical (Rwriurd

Key Word Index-Bleekeria

uitiensis;

I Muy

and

MALCOLM

Engineering, 1973.

Apocynaceae;

alkaloids;

SAINSBURV

University

Accrpted

FROM

of Bath. Somerset,

BA2 7AY

30 June 1973)

carapanaubine;

isoreserpiline;

isoreserpihne-$-

indoxyl ; bleekerine. Abstract-The stem-barkof Bleekeria uitiensis A. C. Smith contains traces of the oxindole alkaloid carapanaubine as well as isoreserpiline-cj/-indoxyl. The co-occurrence of these two compounds is of probable biosynthetic significance, representing alternative oxidative rearrangement products of the alkaloid isoreserpiline. IN PREVIOUS work’,’ we have shown that the Fijian plant Bleekeria uitiensis(Markgraf) A. C. Smith, Apocynaceae. is an abundant source of 9-methoxyellipticine (1) and isoreserpiline (2). A number of minor alkaloids are also present including holeinine (3), isoreserpiline-$-indoxyl (4) and bleekerine (5).

(2)

(4)

(6)

(5)

In this communication we report the isolation of the oxindole alkaloid carapanaubine (6) from the stem-bark of B. uitiensis. Although this alkaloid has been isolated previously from Apocynaceous plants3 the discovery of it together with isoreserpiline-$-indoxyl is unique and interesting. The primary site of synthesis of isoreserpiline in B. uitirnsis appears to be the leaves. In otherpartsoftheplanttheconcentration ismuch lower.2Although thisalkaloidisinvariably * Part

III

in the stxic‘s “E\tractives

of the Ochrosiinae”.

For Part II set Ref. 7.

’

KILMI\STLK.K. N.. SAINSBLKY.M. and Wtea. B. (1972) Ph!rochrrrlistl.? 11, 389. ’ SAINSBURY,M. and WEBR. B. (1972) Phyrochevzistry Ii, 2337. 3 GILBERT.B., BRISSOLESE, J. A., FINCH, N.. TAYLOR, W. I., BUDZIKIEWICZ,H., WILSON. J. M. and

(1963) J. .4111.Chrrn. Sot. 85, 1523. 503

DIERASSI, C.

accompanied by tracts ofisoreserpilille-I//-illdox~i, holeininc. bleekerine and carapanaubine have only been detected in the stem-bark. The regular co-occurrence of isoreserpiline and isoreserpiline-$-indoxyl lend support to the view that the latter is an artifact; nevertheless the distinctive chromatographic behaviour of this compound has enabled its detection in the very earliest phase of the extraction procedure. a fact which tends to substantiate its authenticity. It stems probable that carapanaubinc and isoreserpiline-~-indo~~l form from isorescrpiline by alternative oxidativc rearrangements. Such rcarrangcmcnts have been observed in rir~‘o; thus when the acetoxyindoleine (7, X = OAc) formed by lead ten-a-acetate oxidation of isoreserpiline, is treated with methanolic acetic acid carapanaubine is produced,” but if base is employed isoreserpiline-ti-indoxyl results. Since \ve have shown’ that lead tetra-acetate oxidation of isorcserpiline yields the zwitterionic alkaloid bleekerine, there appears to be a direct correlation between irr citro and irz ciao reactions leading from isoreserpiline to bleekerine, carapanaubine and isoreserpiline-$-indoxyl. It seems likely that the biosynthetic routes leading to the ellipticine and isoreserpiline alkaloids are also intimately linked, but unfortunately. at the present time. there is no experimental evidence to verify this conclusion.

lsoreserpiline (2)

i

i

i

Bleekerlne

Caropanoubine

Isoreserpiline-~-indoxyl

(5)

(61

(41 %Flt

511 1. oXli)~Al-I\,

l’ROI)I

< 15 Ol- ISORt $I KI’II i\l.

EXPERIMENTAL Ground stem-bark (2 kg) was extracted exhaustively with MeOH (6 1.) and the cont. extract chromatographed on alumina (Merck neutral grade I), eluting firstly with light petrol. (60-80’). then with light petrol.-CHCl, mixtures. Carapanaubine (2,5 mg) was isolated from fractions eluted with X0 -loo:,, CHCl,-light petrol. where it occurred as a minor component: the principal extractives being sterols and 9-methoxyellipticine. Carapanaubine. m.p. 218-220 . m.m.p. 219.-220 (lit..3 221-223 ‘) >.f,B”. 244 (log E 3.20) nm was obtained as colourless prisms. MS: m!e428,1948 (Found: C. 64.5; H. 6.6; N, 6.5. Calc. for CL3H2sN-Oh: C, 64.5: H. 6.6: N. 6~5”,~).This material has identical TLC properties. in three solvent qstems. to an authentic sample. generously provided by Dr. 8. Gilbert. Centro de Pcsquisas de Productos Naturals. Brazil. In additron. the circular dichroism curve” of it the alkaloid IS superimposable upon that recorded h! Pou\sc~ (‘I U/ _ for car,lll;rn;ctihiiIc. thus distinguishing from the ~tlti‘rnittr\c dl;l~tcrcoi\ilineric I;irmr .~~k/fo~~lrrl~r,,,~t~t.~

material

The authors thank Dr. K. Jewsers. Tropical Products and the Cancer Research Campaign for financial support.

institute.

’ FIhCf-1. N.. (71 ~$1\III.\. V. u’.. HSL I. H. C. and TA> LOI<.W. I. ( 1963 I J. l/x 5 FINCH. N. TAYLOK. W. 1. and LI.SI~A~ w. P. R. (1963) E.~p~icr~riu 19, 296.

London

for the gtft of plant

C‘iir~ir~. SW X5. Ii20

’ We are grateful to Dr. P. M. Scopes. Westfield College. London for determining thts spectrum. ’ POtW:T. .T.-L.. Porsso\. J.. SI-II\I. R. J. and Sfia\fw. M. (1967) Rtrii Si,c. C‘hirii.f-r. 8, 17th