~ Pergamon PII: S0031-9422(97)00072-1 Phytochemistry, Vol. 45, No. 4, pp. 847-850, 1997 <'~ 1997 Elsevier Science Ltd All rights reserved. Printed in Great Britain 0031 9422,/97 $17.00+0.00 METHOXYLATED QUINOLIZIDINE ALKALOIDS FROM ACOSMIUM PANAMENSE NIGEL C. VEITCH*, BRIAN L. GOODWIN'~,GEOFFREYC. KITE and MONIQUE S. J. SIMMONDS Jodrell Laboratory, Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3DS, U.K. (Received in revisedform 3 December 1996) Key Word Index--Acosmium panamense; Leguminosae; bark; quinolizidine alkaloids; 13fl- methoxylupanine; 4a-hydroxy- 13fl-methoxylupanine; 3fl,4ct-dihydroxy-13fl-methoxylupanine. Abstract--Two new quinolizidine alkaloids isolated from bark material of Acosmium panamense were identified as 4~-hydroxy-13fl-methoxylupanine and 3/~,4~-dihydroxy-13//-methoxylupanine by spectroscopic methods. Full IH and 13C NMR spectroscopic assignments are presented for the closely related alkaloid, 13/%methoxy- lupanine, which also occurs in this species. © 1997 Elsevier Science Ltd. All rights reserved INTRODUCTION Acosmium Schott is a genus of ca 16 species of trees within the tribe Sophoreae, with a geographical dis- tribution from southern Mexico to northern Argen- tina [1]. Previous phytochemicai work on this genus is limited, with records published for only two species, .4. dasycarpum subsp, glabratum (Benth.) Yakovlev and .4. panamense (Benth.) Yakovlev [2]. The pow- dered bark of the latter species was at one time used as a drug in the U.S.A. under the name of Cascara Amarga [3] and various properties have been ascribed to it, including some efficacy in the treatment of syphilis [4, 5], chronic skin diseases, anaemia and colds [6, 7]. A number of quinolizidine alkaloids have since been isolated from the bark of A. panamense, includ- ing a new natural product, 4~-hydroxysparteine [8], and the Ormosia-type quinolizidine alkaloid, (___)-6- epipodopetaline, known earlier as sweetinine [9, 10]. However, analysis of a crude alkaloidal extract of A. panamense bark by GC-mass spectrometry at the outset of the present investigation demonstrated the presence of many additional quinolizidine alkaloids. Among these were two new, substituted lupanine derivatives, 4c~-hydroxy-13fl-methoxylupanine and 3fl,4~-dihydroxy-13fl-methoxylupanine. A third derivative, 13fl-methoxylupanine, has been reported previously from a number of sources, including A. panamense [11, 12], although a full spectroscopic characterization has not been given in the literature. Complete IH and t3C NMR assignments, together * Author to whom correspondence should be addressed. t Present address: Department of Pharmacy, King's Col- lege London, Manresa Road, London SW3 6LX, U.K. with mass spectral data, are therefore provided for all three compounds, in order to facilitate their identi- fication in other species where quinolizidine alkaloids are prevalent. RESULTS AND DISCUSSION Compounds 1 3 were isolated as minor alkaloidal components from a 70% methanol extract of pow- dered A. panamense bark by means of solvent extrac- tion, column chromatography on silica gel and pre- parative TLC. Their structures were determined unambiguously using one- and two-dimensional tH and ~C NMR experiments in conjunction with mass spectral data. All 13C NMR assignments are presented in Table 1. The mass spectrum of 1 indicated a [M] + ion at m/z 278 and a prominent fragment ion at m/z 247 cor- responding to loss of a methoxyl group. In addition, comparison of the fragmentation pattern with litera- ture data revealed a high degree of similarity with 13- epimethoxylupanine [13]. The tH and ~3C NMR data obtained for 1 was typical of that recorded previously for lupanine derivatives [11]. Substitution of the lupanine skeleton by a methoxyl group was evident from the additional ~H and ~3C resonances at 6 3.34 (3H, s) and 6 55.4, respectively. An empirical formula for 1 of CI6Hz6N202 was readily deduced from DEPT spectra, with a proposed Mr of 278.39, in agreement with the mass spectral data. The ~3C NMR spectrum of 1 closely matched that of 13fl-hydroxylupanine [14], with the notable exception of the C-13 resonance ( + 9.5 ppm) and to a lesser extent those of C-12 (- 2.9 ppm) and C-14 (-2.7 ppm), thus supporting the location of the methoxyl group at C-13. A complete 847