Structures of tabernaelegantines Andash;D and tabernaelegantinines A and B, new indole alkaloids fromTabernaemontana elegans

摘要

1432 J.C.S. Perkin IStructures of Tabernaelegantines A-D and Tabernaelegantinines A and B,New lndole Alkaloids from Tabernaemontana eiegansBy Ezio Bombardelli, Attilio Bonati, Bruno Gabetta," Ernest0 M. Martinelli, and Giuseppe M ustich,Bruno Danieli," lstituto di Chimica Organica, Universita degli Studi, Centro per lo Studio della Chimica delleSostanze Organiche Naturali del C.N.R., 201 33 Milan, ItalyThe structures of tabernaelegantines A-D (l )-(4) and tabernaelegantinines A and B (5)-(6), new 'dimeric'indole alkaloids isolated from the root bark of Tabernaemontana elegans Stapf. h(we been determined from theiri.r., u.v., mass, and l H and 13C n.m.r. spectra. The structural elucidation required the analysis of the carbon-13spectra of voacangine, dregaminol, and tabernaemontanol.The 13C n.rn.r. investigation supports the revision ofthe reported configurations at C-20 of dregamine and tabernaemontanine.Research Laboratories, lnverni della Beffa, Via Ripamonti 99, 201 41 Milan, ItalyEXTRACTION of the root bark of Tabernaemontana elegansStapf., an Apocynaceous tree growing in Mozambique,with methanol affords a complex mixture of tertiarybases from which seven new indole alkaloids have beenobtained. The isolation procedure has been describedalready,l and the present paper is concerned with theelucidation of structures (1)-(6) for six of the new bases,designated, respectively, tabernaelegantines A (1) , B (2),C (3), and D (4) and tabernaelegantinines A (5) and B (6).These alkaloids are new members of the voacarnine (7)group; that is, they are ' dimer ' alkaloids composed ofcoupled vobasine-like and ibogamine-like units.Inparticular, the structures of the tabernaelegantininesA (5) and B (6) are of considerable biogenetic significanceas these two bases contain an extra C , unit in the ali-phatic portion of the ibogamine unit.The physical constants and the U.V. absorption maximaof the six alkaloids are reported in Table 1. The fourtabernaelegantines have the molecular formula C,H,N40, (high resolution mass spectra) and show verysimilar spectral properties. Their U.V. spectra (inneutral 95 ethanol) exhibit small differences in intensi-ties only. In particular, tabernaelegantines B (2) andD (4) show at 296 nm a maximum slightly more intensethan the absorption at 287 nm, whereas the isomersA (1) and C (3) display an opposite behaviour in thisregion.However all the spectra are consistent with thepresence of indole or alkoxyindole chromophores.The i.r. spectra also are very similar, the most promin-ent bands being at 3 450-3 370 (NH) and 1 730 cm-l1 B. Gabetta, E. M. Martinelli, and G. Mustich, Fitotevupiu,1975, 46, 1951976TABLE 1Physical constants and U.V. spectraM.p. ("C) a1D2' (")Alkaloid (solvent) (in CHC1,) RF * knax. (95 EtOH)/nm (1 4Tabernaelegantine A (1) 231 (MeOH) - 31.8 0.63 224 (4.70), 285 (4.14), 293 (4.10)Tabernaelegantine B (2) 199 (Me,CO) + 14.4 0.48 227 (4.71), 287 (4.09), 296 (4.23)Tabernaelegantine C (3) 171 (MeOH) - 36.8 0.35 224 (4.76), 285 (4.18), 293 (4.16)Tabernaelegantine D (4) 206 (MeOH) + 11.3 0.16 226 (4.73), 287 (4.13), 296 (4.16)Tabernaelegantinine A (5) 160 (n-C,H,,) - 53.7 0.60 224 (4.74). 285 (4.18), 293 (4.15)Tabernaelegantinine B (6) 215 (MeOH) + 39.1 0.11 227 (4.75), 287 (4.14), 295 (4.18)* On silica gel G (Merck F254) ; eluant n-hexane-acetone (I : I).1433(CO).As the mass spectral fragmentation patterns are,from a qualitative point of view, identical (Table 2), allthese data indicate that tabernaelegantines A-D are( 1 ) R' = p - E t , R 2 = H(3) R ' = w - - E ~ , R * = H( 5 ) R' p - Et, R 2 = CHiCOMe- HN( 2 ) R' p - E t ,( 4 ) R' = Ct-Et,R 2 = HR 2 = HMeo2c* (6) R' = f3 - E t , R2 = CHiCOMeTABLE 2Mass spectral data*Relative intensities (yo)closely related. The mass spectra of (1)-(4) all containpeaks at m/e 675 (C4,H,,N,O5), 648 (C,H5,N403), 524I.+Me02C 1.' MeO,C, I bsol;M eOCOzMe k'H IMe 0f L$ MeMe02C L bsol;MeI f !wle (1) (2) (3) (4)675 ion (a) 4 4 7 3511 ( d ; R = H) 14 38 80 100196 ( f )720 (M+ + Me - H) 28 32706 (M+) 81 62 36 80648 (b) 3 4 3 8524 (c; R = H) 100 100 100 98393(e; R = H) 11 67 13 3220 65 13 1846 96 45 48 Me19 50 26 3514 38 16 21+l I t :ti (0124 (2)122 (i) 16 41 18 23 Me02C* Obtained a t 70 eV; filament current 100 FA; vaporizationtemperature 130-140 "C.li I li 1434 J.C.S. Perkin I( C33H,N303) , 51 (c32H37N303) 393 (C,H,N203) , l96(C,,H1,NO,), 182 (C,amp;,,NO,), 136 (C,H,,N), 124(C,H,,N), and 122 (C,H,,N).The peaks with lower m/evalues are of particular diagnostic value, as fragments atm/e 196 ion (f), 182 (g), and 124 (i) and at m/e 136 (h)and 122 ( j ) occur 293 in the mass spectra of the 19,20-di-hydrovobasinols (8) and (9) and voacangine (lo), re-spectively, which suggests that the four tabernaelegan-tines are built up from 19,20-dihydrovobasine- andvoacangine-like units. The most representative lsquo; dimer rsquo;alkaloid of this type is voacamine (7),, the mass spectrumof which also shows peaks at m/e 524 ion (c), 511 (d), and122 ( j ) , whereas its molecular ion and the ions (a), (b),@ C02FvI e19linkage1 i nkagelinkageatatatc-11rsquo;C - 111 19,20c - 9rsquo;dihydrobut differs in physical properties from the taberna-elegantines.The proton n.m.r.spectra of (1)-(4) also are com-patible with 19,20-dihydrovoacamine-like structures.They are characterized (Table 3) by four three-protonsinglets near 6 3.9,3.7, 2.6, and 2.5. These signals fall inthe regions where, respectively, the OMe and C0,Mefunctions and the NMe and C0,Me groups of the voa-cangine and vobasine portions re~onate,~ the high-fieldshift of the C02Me signal of the vobasine unit arisingfrom the diamagnetic anisotropy effect of the indolenucleus. Furthermore, signals for two low-field protons(NH) and six aromatic protons, and a one-proton signalnear 6 5 C(3)H are present ; the most relevant change incomparison with voacamine is the lack of the ethylidenesignals and the appearance of an additional ethyl groupin the high-field region.The aromatic patterns of (1)and (3) show the presence of two ortho-protons, whereasthe spectra of (2) and (4) contain, like that of voacamine,a one-proton singlet at 6.78 p.p.m. Alkaloids of thevoacamine group are known to isomerize in acidic media.4For instance, voacamidine (12) turns into voacamine (7)on refluxing in 2~-hydrochlork acid.5 The isomerizationis partially accompanied by the cleavage of the 3,9rsquo;-linkage, so that from this reaction the ibogamine com-ponent of the lsquo; dimer rsquo; can also be obtained.6 After re-fluxing in methanol and concentrated hydrochloric acid,tabernaelegantines B (2) and D (4) were unchanged, butthe same acidic treatment converted tabernaelegantinesA (1) and C (3) into (2) and (a), respectively.In bothcases minor amounts of isovoacangine (13) were isolated.If now we consider the aromatic patterns of the protonspectra, the evidence so far discussed indicates that thehydrovobasine unit, connected through a linkage involv-ing C-3 and C-12rsquo; (l) and (3) or C-10rsquo; (2) and (4),respectively. If we assign p-orientations to the C-3protons of the four isomers on the basis of the argumentsadvanced by Buchi? there remains the possibility ofisomerism only at C-20; that is tabernaelegantines A-Dmust contain either a dregamine (14) or a tabernaemont-anine (15) unit.(10) Rrsquo;= OMe, R2= H, R3= CO2ble R4= H The configuration at C-20 for the latter two bases was(13) Rrsquo;= H, R2= OMe, R3= C02Me, R4= H first investigated by Renner and his co-workers,2 whosuggested the p-axial and a-equatorial orientations for (17) Rrsquo;= OMe, R2= H.R3= H, rsquo; RL= H the respective ethyl side chains. A recent X-ray crystal-(18) R1= H, R2= H, R3= C02Me,rsquo; RL= H, 15,20-didehydro lographic study has led to the revision of these argu-(19) Rrsquo;= OMe, R2= H, R3= C02Me, RL= H, 3-rsquo;Hd ments; thus dregamine and tabernaernontanine must(20) R1= H, R2= H, R3= C02Me, @= CHiCOMe be assigned the absolute configurations shown in formu-MeOzC (8) Rrsquo; = a - Et R 2 = p -OH(9) Rrsquo; = p - Et , ~2 = p - OH(1.4) R rsquo; = O( - Et, R2 = 0( 1 5 ) R rsquo; = p - E t , R 2 = 0(16) R t = EtCH:, R 2 = -OH four alkaloids contain an isovoacangine and a 19,20-di-(f), (g), and (i) contain two less hydrogen atoms thanthose from the tabernaelegantines, owing to the presenceof the 19,20-double bond. Catalytic hydrogenation ofvoacamine affords a dihydro-derivative (1 1) , whichexhibits the same mass spectral fragmentation pattern2 U.Renner, D. A. Prins, A. I. Burlingame, and K. Biemann,Helv. Chim. A d a , 1963, 46, 2186.9 H. Budzikiewicz, C. Djerassi, and D. H. Williams, lsquo; StructureElucidation of Natural Products by Mass Spectrometry,rsquo; Holden-Day, San Francisco, 1964, vol. I, p. 67.lae (14) and (15).Dregamine and tabernaemontanine can be spectro-scopically differentiated by the high-field regions of their100 MHz lH n.m.r. spectra. The spectrum of dregaminein CDCl, contains two well separated signals at 6 1.88 andG. Buchi, R. E. Manning, and S. A. Monti, J . Amer. Chm.SOC..1964, 86, 4631.ti U. Renner and H. Fritz, Tetrahedron Letters, 1964, 283.6 W. Winkler, Arch. Pharm., 1962, 295, 895.7 A. Husson, Y. Langlois, C . Riche, H. P. Husson, andP. Potier, Tetrahedron, 1973, 29, 30951976 1435TABLE 31H N.m.r. spectra (6 values) *(4)7.74 7.687.56 7.58 7.597.2-6.9 C 6.78 d 7.2-6.9 rsquo; 6.786.83 a 6.845.29(m) 5.06 (m) 5.27 6 5.04(m)3.91br f 3.96 3.92br g 3.96(3)7.64(1) (2)7.24 7.14-6.90 7.26 * 7.14-6.84 lsquo; i NHArHC(3)HArOMeC0,Me 3.70NMe 2.57C0,Me 2.48CH,Me 0.94CH,Me 0.80 {COMe* 100 MHz; solvent CDCl,;a 1 H, d, J 9 Hz. b 5 H, m.Carbon23567891011121314151618192021C0,MeC0,MeNMe2lsquo;3rsquo;5lsquo;6rsquo;7lsquo;8rsquo;9rsquo;10rsquo;11rsquo;12rsquo;13rsquo;14rsquo;15rsquo;16rsquo;17rsquo;18rsquo;19rsquo;20rsquo;21rsquo;C0,Mersquo;C0,Mersquo;ArOMeCH,.COMeCH,COMeCH,CO Me(8)137.166.959.019.3107.8129.4118.0119.1121.9110.6135.830.628.950.311.623.643.849.3175.450.342.43.672.572.430.94 80.86 {Me,Si standard.C 4 HI m.(9)137.167.159.217.7107.9129.4118.0119.1121.9110.6135.838.230.344.212.825.642.947.13176.050.442.93.70 3.672.64 2.632.52 2.440.92 { 0.92 i0.81 J 0.86 8(6)7.74 7.637.55 7.597.23 a 7.6-6.84 rsquo;7.15-6.9 0 6.79 d6.82 45.27(m) 5.04 ( m)3.97 3.93br h(5)3.712.582.520.94 80.80 62.003.662.632.440.93 i0.86 i2.09a l H , s .~ d d , J13and4Hz. f Wt5Hz. g Wi9Hz. hW+8Hz. i t , J 7 H z .TABLE 413C N.m.r.data (6 values) *(10)137.851.753.322.2110.2129.3100.9154.1111.3111.9130.927.432.155.236.511.726.839.157.552.6175.956.0(1)136.334.759.417.9109.1129.7118.2119.4122.1110.0137.036.935.244.012.925.743.147.0172.650.043.1136.351.363.022.1110.5124.6117.1105.1152.1114.9135.427.232.054.735.011.626.638.967.652.3174.957.0(2)135.635.159.717.6110.3130.4118.3118.6121.5110.0136.237.135.144.113.025.843.247.2172.750.043.2135.151.653.222.2111.1122.9117.6127.9163.893.0138.227.532.255.236.511.726.839.357.752.5176.256.0(3)136.234.759.219.5109.0129.6118.1119.4122.1110.0136.929.233.149.911.423.543.949.5172.049.942.5136.251.353.022.1110.3124.5117.1105.1152.1115.1135.327.131.954.635.111.626.638.957.652.3175.056.8(4)135.936.659.519.9110.0129.5117.9119.5122.1110.4136.231.531.949.810.722.941.648.4169.550.341.0135.551.553.422.0110.1122.7117.3126.9153.493.2139.027.331.854.936.111.726.839.157.652.7175.856.1(5)136.034.959.217.8108.7129.4117.8119.1121.9109.9136.636.835.243.812.825.643.046.7172.249.843.0136.054.651.322.0110.1124.4116.9104.9161.8114.7135.230.626.654.235.811.626.638.258.652.2174.456.746.7208.230.6(6)135.237.059.319.3110.6129.9117.2118.5121.1109.7135.930.931.849.711.423.543.849.7171.549.742.3134.855.151.422.0109.7122.4118.0127.6153.392.7137.932.927.054.737.511.726.738.458.352.4175.555.846.7208.330.9* Solvent CDCl,; Fourier transform instrument operating at 25.2 MHz ; standard internal Me,SiJ.C.S.Perkin I1.32 for the C-19 and C-20 protons, which, in the spec-trum of tabernaemontanine, form into a complex multi-plet centred at 6 1.50. However, these data cannot beused for determining the configurations at C-20 of com-pounds (1)-(4) owing to the complexity of these regionsin the spectra of the lsquo; dimersrsquo;. Hence, as carbon-13spectroscopy is much more sensitive to changes in stericrelationship between groups, an examination of thecarbon spectra of dregaminol (8) and tabernaemontanol(9) was undertaken.The results of this investigation aresummarized in Table 4.The aromatic carbon shifts of (8) and (9) are consistentwith the presence of indole units and can be assigned onthe basis of chemical shift theory.8 The non-aromaticregions are characterized by the presence of five doublets,four triplets, three quartets, and one singlet. The shiftsof the 0- and C-methyl groups and the carbonylfunction are derived from chemical shift theory. Asregards the methyne resonances, the assignments of C-3,-5, -15, and -20 the last occurs in the aromatic region inthe spectrum of vobasinol (l6) are based on simple elec-tronegativity considerations.The remaining methynecarbon, C-16, resonates at 6 44.2 in (9) and at 50.3 in (8).Molecular models of both (8) and (9) show that, if theethyl group at C-20 has a p-axial orientation, C-16experiences a strong steric interaction with C-19.Therefore, the high-field resonance of C-16 in (9) indicatesthat the ethyl side chain is p-oriented.The triplet resonances are due to C-21, -14, -19, and -6.The two spectra show signals in the regions 6 48 (C-21),24 C-19, shifted downfield in the spectrum of (16), and18 (C-6), whereas the C-14 signal falls at 6 30.6 and 38.2in (8) and (9), respectively. The resonances associatedwith C-14 are correctly assigned, as they are the solesignals which show significant shifts in the spectra of theparent compounds, dregamine (14) and tabernaemont-anine (15) (39.4 and 45.8, respectively).The markeddifference in C-14 chemical shifts also arises from thestereochemistry at C-20: if the ethyl side chain isor-equatorially oriented, C-19 interacts sterically with theC(14)-cc-H linkage and, as a consequence, the C-14 signalmoves to higher field. Hence, carbon-13 spectroscopyalso points to the revision of the original stereochemicalassignments and, on the basis of the observed differencesin chemical shift of C-14 and -16, this technique shouldprovide valuable information about the stereochemistryat C-20 of the tabernaelegantines. However, unam-biguous carbon signal assignment of the spectra of thesebases required examination of the spectrum of isovo-acangine (13) as well.Owing to the extremely smallamount of (13) at our disposal, the investigation wascarried out on its isomer, voacangine (lo), which pos-sesses the same aliphatic skeleton. Inspection of thecarbon spectrum of ibogaine (17) also appeared useful, asthe removal of the methoxycarbonyl function from the8 G. W. Gribble, R. B. Nelson, J. L. Johnson, and G. C. Levy,J . Org. Chem., 1976, 40, 372.9 G. C. Levy and G. L. NeIson, lsquo; Carbon-13 Nuclear MagneticResonance for Organic Chemists,rsquo; Wiley-Interscience, New York,1972, p. 48.voacangine skeleton predictably affects only the C-20 and-17 signals, which are expected9 to move to lower andhigher field, respectively.Additional evidence for thecorrectness of the carbon shift assignments of thequinuclidine system was also provided by inspection ofthe spectrum of catharanthine (18).The aromatic carbon shifts of voacangine are consistentwith the presence of a 10-methoxyindole unit (Table 4).The non-aromatic region contains signals for thirteencarbon atoms (three quarters, six triplets, three doublets,and one singlet). Apart from the C-16 and methylsignals, which are easily attributable on the basis of theirmultiplicity and of chemical shift theory, the doubletresonances are for C-21, -20, and -14 and are readilyassigned since they have markedly different chemicalshifts: C-21 (6 57.5) is linked to Nb whereas the C-20signal (39.1) is shifted downfield relative to C-14 (27.4)owing to the @-effect of C-21.In the spectrum ofibogaine (17), C-14 (8 26.6) and C-21 (57.6) show nosignificant change, whereas C-20 suffers the expecteddownfield shift (2 p.p.m.). Furthermore, the high-fieldregion of the catharantine (18) spectrum containsdoublets for only two carbon atoms, C-21 (6 61.9) andThe six triplet resonances of the voacangine spectrumare for C-3, -5, -6, -15, -17, and -19. C-3 and -5 are linkedto the Nb and their signals are shifted downfield (6 53.3and 51.7) relative to those of the other methylene carbonatoms. In the ibogaine (17) spectrum, these two signalsfall at 54.3 and 50.1, but it is possible to allocate theseresonances by an investigation of the spectrum of3-2H,ibogaine (19) ,lo which indicates that the low-fieldsignal must be attributed to C-5.The C-17 resonance at 6 36.5 in the spectrum ofvoacangine is distinguished from the other methylenesignals by its high-field shift (34.1) in the spectrum ofibogaine, whereas, of C-15 and -19, the signal of theformer is expected to be the farthest downfield as it issubject to many p-effects.Furthermore, in the cathar-anthine spectrum the C-15 signal moves to 6 123.5,whereas C-19 still resonates in the 6 26 region.With the chemical shifts of the models (euro;9, (9), and (10)established, the 13C n.m.r. analysis of the lsquo;dimersrsquo; issimple. The aromatic signals corresponding to the dreg-amine or tabernaemontanine units remain almost un-affected, and the substitution at C-10rsquo; or -12rsquo; can beeasily deduced.In fact, in the case of a C-10rsquo; linkage ahigh-field doublet is present at 6 ca. 93, characteristic l1of C-12rsquo; of an 11rsquo;-methoxy-substituted unit, whereasC-10rsquo; resonates as a singlet a t 6 ca. 127. If the substi-tution is at C-12rsquo;, C-10rsquo; and -12lsquo; resonate at ca. 105 and115, respectively.Of the saturated carbon signals, only the resonances ofC-3, -14, and -15 are perturbed by the replacement of theC-3 hydroxy-group of (8) and (9) (upfield shifts for C-3C-14 (30.9).lo M. F. Bartlett, D. F. Dickel, and W. J. Taylor, J . Amer.11 D. W. Cochran, P1i.D. Dissertation, Indiana University,Chem. SOC., 1958, 80, 126.19711976and -14, downfield shift for C-15).12 The remainingsignals can be easily assigned by a simple subtractiveprocess.The stereochemistry at C-20 of (1)-(4) can be deduced,from the above considerations.Tabernaelegantines A(1) and B (2) show C-16 resonances at 6 44.0 and 44.1, andthose of C-14 at 36.8 and 37.1, whereas in tabernaelegan-tines C (3) and D (4) these carbons resonate at 49.9 and49.8, and at 29.2 and 31.5, respectively. These shiftssupport p- and a-orientations for the ethyl side chains,respectively, as shown in structures (1)-(4).In addition to the aromatic patterns of the proton andcarbon spectra, the differences in substitution at C-10rsquo; or-12lsquo; are reflected in (i) the C-3 proton resonance (ca. 0.23p.p.m. upfield shift if the substitution is at C-10rsquo;) ; (ii) theshape of the 290 nm region of the U.V.spectra (Table 1);(iii) the shape of the 11rsquo;-methoxy-signal in the protonspectra dramatic broadening (Table 3) if the substitutionis at C-lorsquo;; (iv) the possibility of interconversion be-tween the two pairs (1) and (2), and (3) and (4), as only a3,12rsquo;-bond can be converted into a 3,lOrsquo;-bond; (v) amass spectral peak 14 mass units greater than themolecular weight if the substitution is at C-10rsquo; (Table 2).The mass spectrum of voacamine also shows an M +- 14peak arising from intermolecular methyl transfer involv-ing the voacangine methoxycarbonyl group as methyldonor and Nb of the vobasinol component as acceptor.13The quaternary ammonium salt thus formed can undergoKofrnann degradation, the proton abstractor being thecarboxylate anion.Molecular models of the tabernaelegantines indicatethat rotation about the 3,12rsquo;-bond of (1) and (3) issterically more inhibited than that around the 3,lOrsquo;-bondof (2) and (4); this accounts for the possibility of con-version in acidic media of the former alkaloids into themore stable ones (2) and (4).Furthermore, the iso-voacangine methoxycarbonyl groups of (1) and (3) appearto be crowded by the dihydrovobasinol units, and conse-quently unavailable for ion-molecule collisions in themass spectrometer. No transmethylation processes arein fact observed in the case of (1) and (3), even at highervaporization temperatures, whereas the intensities of theiW + 14 peaks exhibited by (2) and (4) appear to be de-pendent on vaporization temperature (the spectra re-ported in Table 2 were recorded at 130-140 ldquo;C).In addition, the molecular models show that in themost stable conformations of (2) and (4) the aromaticrnethoxy-groups of the isovoacangine units are linked tothe indole NH group of the dihydrovobasine componentby strong hydrogen bonding, which causes broadening ofthe OMe signals in the proton spectra.On the otherhand, the restricted rotation about the 3,12rsquo;-bonds of (1)and (3) inhibits the formation of such intramolecularhydrogen bonds, so that the shapes of the methoxy-signals are in this case unaffected.Tabernaelegantinines A (5) and B (6) have the molec-12 J. D. Roberts, F. J. Weigert, J. I. Kroschwitz, and H. J.l3 D. W. Thomas and K. Biemann, J . Amer. Chem.SOC., 1965,Reich, J . Amer. Chem. SOC., 1970, 92, 1338.87, 5447.1437ular formula C,H5,N,0,. They are two further mem-bers of the voacamine family, as suggested by theirproton and carbon n.m.r. spectral properties (Tables 3and 4). In particular the aromatic regions of the carbonspectra are almost identical with those of (1) and (2),respectively. In addition, the mass spectrum of taberna-egantinine B (6) contains, like (2) and (4), the ion at m/e776 (M + 14, 23) indicating the presence of a 3,12rsquo;-bond.In comparison to the tabernaelegantines , the taberna-elegantinines (5) and (6) contain three additional carbonatoms, involved in a CH,*CO*CH, grouping (3H as asinglet in the 6 2 region of the proton spectra; CO at 208,CH, at 46, and CH, at 6 30 in the carbon spectra).Thisgrouping must be placed in the isovoacangine unit as, inaddition to the peaks at m/e 762 (M+, 87 and 48,respectively), 731 (M - Me, 6 and 5), 719 (M -COMe, 3 and 12), 705 (M - CH,*COMe, 26 and 15),673 (M - CH,COMe - OMe - H, 12 and 3:4,), 196 ion(f), 26 and 39x1, 182 ion (g), 89 and 95, 136 ion (h),9 and 21y0, 124 ion (i), 9 and 19, and 122 ion ( j ) , 14and 25, the mass spectra of (5) and (6) contain theions (c) (R = CH,COMe, m/e 580, 100, and 8674), (d)(R = CH,-COMe, m/e 567, 13, and loo), and (e)(R = CH,*COMe, mle 449, 7 and 20) shifted by +56m.u. in comparison with the corresponding ions of thetabernaelegantines. Ions at mle 522 (c) - Me,CO, 56and 7oy0 and 509 (d) - Me,CO, 6 and 29) are alsopresent.The aliphatic regions of the carbon spectra show that(5) and (6) possess opposite configurations at C-20.Infact, C-16 and -14 resonate at 6 43.0 and 36.8 in (5), andat 49.7 and 30.9 in (6), in agreement with an axial and anequatorial orientation, respectively, of the C-20 ethylside chains. In addition, a comparison of the carbonshifts of the isovoacangine units of (1)-(4) and (5) and(6) shows that in the tabernaelegantinines one of theaminomethylene carbon signals is a doublet thus in-dicating that the CH,*CO*CH, grouping is at either C-3lsquo;or -5rsquo;. The substitution does not notably affect theresonances of C-6rsquo;, -17lsquo;, and -20lsquo;, whereas those of C-14rsquo;and -15rsquo; suffer, respectively, downfield and upfield shifts.These chemical shift changes can be explained if theCH,*CO*CH, grouping is at position 3rsquo;, as in this caseC-14rsquo; experiences a p-effect and C-15rsquo; interacts stericallywith the substituent and consequently resonates athigher field.The configurations at C-3rsquo; of these alka-loids are therefore those represented in the stereostruc-tures (5) and (6).A compound having an ibogamine-like skeleton carry-ing an extra C, unit has been recently isolated,lP and thelocation of this unit at position 3 has been proposed onthe basis of the chemical reactivity of this centre. Thenature of the tabernaelegantinines suggests that theassignment of structure (20) to this alkaloid is probablycorrect. As acetone has been used for their separation,G. Delle Monache, I.L. Drsquo;Albuquerque, F. Delle Monache,and G. B. Marini-Bettolo, Atti Accad. naz. Lincei, Rend. ClasseS c i . 3 ~ . mat. nut., 1972, 52, 3751438 J.C.S. Perkin Ithe possibility that these alkaloids are artefacts cannotbe e~c1uded.l~ However, if they are genuine products,we consider that nucleophilic attack of an acetoacetyl-CoA unit at C-3 of a 3,4-dehydroibogamine component,followed by decarboxylation, is the most probablemechanism of formation of this kind of compound.EXPERIMENTALIH N.m.r. spectra were determined with a Varian XL-100spectrometer. High resolution mass measurements wereobtained with a Varian MAT 311 instrument. 13C N.m.r.spectra were recorded a t 26.2 MHz with a Varian XL-100instrument equipped with Fourier transform facility.Conversion of Tabernaelegantine A (1) into Taberna-elegantine B (2) .-Tabernaelegantine A (200 mg) dissolvedl5 V. C. Agpada, Y . Morita, V. Renner, M. Hesse, and H.Schmid, Helv. Chim. Acta, 1975, 58, 1001.in methanol (10 ml) and concentrated hydrochloric acid (1ml) was heated under reflux for 24 h. Sodium carbonatesolution and methylene chloride were added and the organicphase was washed with water, dried (Na,SO,), and evapor-ated. The residue was chromatographed on silica gel toafford pure isovoacangine (13) (15 mg) , starting material (75Conversion of Tabernaelegantine C (3) into Taberna-elegantine D (a).-A solution of tabernaelegantine C (50 mg)in methanol (8 ml) and concentrated hydrochloric acid (1 ml)was heated under reflux for 16 h. The mixture was dilutedwith sodium carbonate solution and extracted with methyl-ene chloride, and the extract was evaporated. Preparativet.1.c. {silica gel; EtOAc-MeOH-H20 (100 : 5 : 2) yieldedcompounds (3) (13 mg), (13) (8 mg), and (4) (26 mg).We thank Drs. N. Neuss and I. Scott for samples of Ibogaalkaloids.6/018 Received, 5th January, 19763mg), and (2) (90 mg)