Javacarholine, a new P-carboline alkaloid was isolated from the stem of Picrasma javanica (Simaroubaceae). Its structure was elucidated at the extensive 1~ and 13~ nmr studies involving IH-1H COSY, HSQC and HMBC experiments and X-ray diffraction analysisDuring the alkaloidal investigation of Simaroubaceae plants,l Picrasma javanica BL. was studied. P. javanica is a medium-sized tree found in the New Guineas, Southeast Asia. and India. The decoctions of its bark are used in folk medicine as febrifuge and as a substitute for quinine.2 From the chemical studies of the constituents of P. javanica, a number of quassinoids and alkaloids have been identified.3y4 This paper describes the isolation and structural elucidation of a new P-carbohe alkaloid, javacarboline (1) from the stem of P. javanica, which was collected in Java Island, Indonesia.Compound (1) was obtained as pale-yellow prisms. The molecular formula, C20H20N202, was determined from its positive ion FAB-ms spectrum (m/z 321[M+H]+) and from its I~c nmr spectrum, 12 degrees of unsaturation was inferred. The l3~ and DEPT nmr spectra suggested the presence of three CH3, two CH2, one sp3-c~, five sp2-CH and nine ~~2-~uaterna.r~ crbons. The HsQC~ experiment allowed us to assign and correlate all the protons to corresponding carbons. Their spectrum showed strong absorption due to the imino group (3422 cm-l) and carboxylate ion group (1627, 1236 and 752 cm-I). The uv absorbances (hmax 235. 308, 380 nm) and IH nmr signals in the 6 7.2-7.7 region showed the presence of an indole system andan additional chromophore. The 1~ and 13~ nmr chemical shifts for the C-3 methine proton at 6 5.89 (lH, dd, J=6.1, 1.2 Hz) and the C-4 methylene protons at 6 3.55 (lH, dd, J=16.8, 6.1 Hz) and 3.84 (lH, dd, J=16.8, 1.2 Hz) indicated that the indole system partly consists of a trihydro-a-carboline moiety. The 1~ nmr spectrum identified seven separate spin systems; the protons on C-5 to C-8 were part of an indolic benzene ring and two three-proton singlets at 6 2.47 and 2.84 were assigned to aromatic methyl groups and methylene H-20 (6 2.96, 2H, q, J=7.6 Hz) to methyl H-21 (6 1.21, 3H, t, J=7.6 Hz) protons comprised an ethyl appendage. In addition, the 1~ and 13C nmr spectra of 1 displayed signals for an isolated aromatic methine at C-17 (6~ 8.84, 6~ 143.34) with a large ~JCH coupling constant (184 Hz), indicating a nitrogen atom adjacent to C-17. The signal for a D20-exchangeable proton was observed at 6 11.75 (lH, s, indolic NH). Furthermore, an HMBC~ experiment (Table I) showed that the protonated aromatic carbon C-17 was correlated with H-3 and H-22, and the carboxylate ion group was attached to the C-3 position, whereas two methyls and the ethyl group were connected to quaternary carbons at C-14, C-16, and C-15, respectively. Difference nOe experiments provided further evidence for the structure of 1 shown in Figure 1. All these data indicate that compound (1) has the indolo[2.3-alquinolizine system characteristic of plant alkaloids like flavopereirine7 and ~em~ervirine.8 However, the positive ion FAB-ms of 1 (m/z 641 [2M+H]+ and 321 [M+H]+) suggested that it contained one molecule of dimeric P-carholines. The 13~ nmr spectrum provided evidence for the presence of a symmetry element in the molecule, since only a limited number of signals, assigned as indicated in Table I, could be observed. To confirm this situation for compound (1). a single crystal X-ray diffraction study was carried out and compound (1) was clearly shown to have the racemic form. Figure 2 shows an ORTEP drawing of a 3s-molecule (la). The peak clearly observed near Nl on adifference Fourier map was assigned to the hydrogen atom. The bond lengths of C18-01=1.248(9) A and C18-02=1.231(8) .&indicated a zwitterionic structure of the molecule with a protonated indolic NH group and depmtonated carhoxyl group. The asymmetric unit contained two molecules which form a dimeric system by means of two hydrogen bonds involving a hydrogen atom at N-1 of one molecule and the carhoxylate ion oxygen atom at 0-2 of the second molecule [distance N1-H .,02=2.864(8) A] (Figure 3).Racemization in this compound is clearly the result of la+lb tautomerization (Scheme I), wherein the natural product (la) is compromised by the biosynthetic pathway from L-uyptophan, and the enantiomer of la can, therefore, be formed by the extraction procedure.The new compound was tested for in vino cytotoxicity in human tumor PC-6 cells and a murine lymphocytic leukemia P-388 cells and it was found cytotoxicity at GI50 35.9 @nl and 32.5 pg/ml, respectively.