Isomeric alkaloids

Vallesiachotamine (9) (4), isolated first from Vallesia dichotoma Ruiz and Pav., and characterized as a mixture of formyl rotamers (16), proved to be really a mixture of two geometrically isomeric alkaloids vallesiachotamine (9) and isovallesiachotamine (10) (16a). Recently 9 and 10 were isolated from Strychnos... 

A similar approach, used for the synthesis of the isomeric alkaloids 33a and 33b, has been described in more recent work (85JOC1516, 89TL5659 Scheme 8). 

Isoschumanniophytine was isolated from Schumanniophyton magnificum and originally given structure 30 (77). Another isomeric alkaloid isolated at the same time was first given structure 29 but was subsequently shown to be schumanniophytine (18) (72). 

The beanlike seeds of the trees and shrubs of the genus Erythrina, a member of the legume family, contain substances that possess curare-like activity. The plants are widely distributed in the tropical and subtropical areas of the American continent, Asia, Africa, and Australia, but apparently they are not used by the natives in the preparation of arrow poisons. Of 105 known species, the seeds from more than 50 have been tested, and all were found to contain alkaloids with curariform properties. Erythroidine, from E. americana, was the first crystalline alkaloid of the group to be isolated. It consists of at least two isomeric alkaloids, a and P-erythroidine both are dextrorotatory. Most experimental and clinical study has centered on the b form because it is more readily obtainable in pure state. P-Erythroidine is a tertiary nitrogenous base. Several hydrogenated derivatives of p-erythroidine have been prepared of these, dihydro-P-erythroidine has been studied most carefully and subjected to clinical trial. Conversion of P-erythroidine into the quaternary metho salt (p-erythroidine methiodide) does not enhance, but rather almost entirely, abolishes its curariform activity this constitutes a notable exception to the rule that conversion of many alkaloids into quaternary metho salts results in the appearance of curare-like action. 

Two new isomeric alkaloids have been isolated from the seeds of Crotalaria candicans W. A. 184 by Siddiqi et al.36 For both alkaloids, the difference in chemical shift for the C-9 protons is 0.95 p.p.m., indicating the presence of a macrocyclic diester ring. Both crocandine (64) and isocrocandine (64) yielded... 

An isomeric alkaloid (alkaloid E) was isolated from S. pedunculata and found to be the major alkaloid in S. multiflora R.Br. (55). Values of 4.0 and 11 Hz for J3A suggested that it was the C-3 epimer 81b of schelhammericine. Structure 81b was proved by identification of 3-epischelham-mericine with 2,7-dihydro-3-epischelhammeridine (see Scheme 23) 84). Later on, another group reported the isolation of 81b from P. comosa, and was able to convert 3-epischelhammerine (80b) to 81b by chlorination and reduction, as shown in Scheme 23 (57). Cephalotaxus harringtonia var. harringtonia has also yielded 3-epischelhammericine 91). 

Other alkaloids in the Al(6)-alkene series have been reported. Two isomeric alkaloids (C20H27NO3) were obtained from Cephalotaxus harringtonia K. Koch var. harringtonia. Their spectroscopic properties closely resembled those of schelhammericine except that their NMR spectra revealed the presence of two aromatic methoxyl groups in place of the methylenedioxy group of schelhammericine. The alkaloids were therefore 3-epihomo-2,7-... 

The stem, wood, and bark of Uncaria kawaJcamii contain the two isomeric alkaloids, uncarine-A and uncarine-B, C21H24N2O4 (30, 31), the highest proportion of alkaloids (1.48%) occurring in the bark (31). Uncarine-B has been identified with formosanine (28, 33), which was isolated earlier from Ourouparia formosana (21, 32). The chemical behavior of uncarine-A and formosanine is identical in all respects, and their relationship as stereoisomers is shown by their ready interconversion and equilibration, which frequently hinders the separation and purification of individual isomers. Thus, uncarine-A in hot dilute acetic acid yields formosanine, and the reverse transformation can be achieved by heating formosanine with ether, until it has all been isomerized into the more soluble uncarine-A. Some formosanine is even obtained when uncarine-A is recovered from its hydrochloride, or from the hydrochloride of the related amino acid, by methylation with diazomethane (59). 

Fig. 13.24 ESI-MS and ESI-MS/MS analysisofthe isomeric alkaloids geyerline (top) and nudicauline (bottom) which differ only in the methoxy and acetoxy substitution of C-14 and C-16 (figure 13.19).

In the 1 (ISO s, investigations oi Nuphar hctenm by Aclmiatowicz and Mollowna (5) resulted in the isolation of two isomeric alkaloids, a- and /9-nupharidine, of the empirical formula Ci5H230N. The a-isomer is probably identical with the deoxynupharidine of Kotake et al. 

Elemental analysis and mass spectroscopy of two isomeric alkaloids,... 

Oxidation of bisbenzylisoquinoline alkaloids with potassium permanganate has been found to be controllable enough to permit fission of only one of the two benzylisoquinoline systems. In this way the O-acetyl derivatives of the isomeric alkaloids tiliacorine and dinklacorine have been oxidised to the aldehydo-isoquinolones (67, R =Me, R =Ac) and (67, R =Ac,R =Me) respectively (Shamma and J.E. Foy, J.org.Chem., 1976, 1293 ... 

These structures have been deduced from spectroscopic data and confirmed by the preparation of key alkaloids by the oxidation of known bisbenzylisoquinolines and by interconversions. Baluchistanamine and sindamine have been obtained by oxidation of the isomeric alkaloids oxyacanthine and berbamine, secocepharanthine from cepharanthine and 0-methylpunjabine from... 

Quadrigemine A (27) and Quadrigemine B (28). —These two isomeric alkaloids (C44H50N8, M = 690) occur together with hodgkinsine in Hodgkinsonia frutescens F. Muell. 

Until recently only monomeric indole and oxindole alkaloids had been isolated from the bark and leaves of Uncaria gambir Roxb. (Rubiaceae). Amongst these were alkaloids of the corynantheine and yohimbine types."" However, from a different batch of plant material five new isomeric alkaloids, the roxburghines A—E, C31H32O2N4, have been isolated in 0.0005—0.005 % yield. ... 

The structure of fetidine (284) has been confirmed by mass spectroscopy.257 Examination of the mass spectra of the isomeric alkaloids thalicarpine and thal-melatine, dehydrothalicarpine and dehydrothalmelatine, and thalmetine and thalcimine (thalsimine) gave conclusive structural assignments on the basis of measurements of peak intensity for fragments containing the C=N function.258 O.r.d. studies of a series of bisbenzylisoquinoline alkaloids isolated from Thalictrum species have been recorded.259... 

The isomeric alkaloids 28-deoxyzoanthenamine (8) and 22-epi-28-deoxy-zoanthenamine (9), have the same molecular formula C30H39NOS, which corresponds to one less oxygen atom than is present in zoanthenamine (6). Comparison of the spectral data of 8 and 9 revealed no major difference, except for the chemical shifts of proton and carbon signals associated with the lactone ring. Further studies suggested that the compounds were isomeric at C-22 (22). 

When the aerial parts of Plectronia odorata (Rubiaceae) were treated with ammonia, two new racemic, isomeric alkaloids, plectrodorine (26) and isoplectrodorine (27), were isolated by Koch and co-workers (53). The molecular ion appeared at m/z 223 and corresponded to the formula... 

In order to compare synthetic ifflaiamine with the natural alkaloid, Chamberlain and Grundon (198, 199) reexamined a crude alkaloid extract derived from the wood of Flindersia ifflaiana and obtained two isomeric alkaloids. Ifflaiamine (264) mp 122-125° [a]D-6.2° in methanol and -9.15° in chloroform picrate, mp 189-192° had properties different from those reported earlier (Volume IX). The second alkaloid (mp 53-54° picrate, mp 188-191°) was shown to be the 1,2-dimethylallyl derivative 267 by comparison with the synthetic racemate (mp 106-108° picrate, mp 186-190°). The alkaloid was levorotatory, but too little was available to obtain an accurate value of the specific rotation. 

Pseudaconine is the parent of four ester-alkaloids found in nature two of these, pseudaconitine (54) and a-pseudaconitine (61), are certainly isomeric since on hydrolysis they both yield acetic acid, 3,4-dimethoxy-benzoic acid, and pseudaconine. The physical properties of the two isomeric alkaloids and their salts are very similar (cf. Table 13), and it appears (61) that they may differ only in the position of attachment of the 3,4-dimethoxybenzoyl group since the difference between the 3,4-dimethoxybenzoylpseudaconines (the intermediate hydrolysis products) is much greater than that between the diesters. 

By similar arguments, the structure of the isomeric alkaloid isotriphyophylline was interpreted as 24, with a relative cis configuration of the two secondary methyl groups, because its N-benzyl derivative showed a singlet in its 60-MHz NMR (33). The possibility that isotriphyophylline might be, for example, the atropisomer of 23 was not regarded. 

The structure of the alkaloids will be considered in the above order of increasing complexity. Related and isomeric alkaloids will be discussed within these five main groups lupinine, cytisine, sparteine, lupanine, and anagyrine. 

The first crystalline pharmacologically active alkaloid was isolated from Erythrina americana mentioned above (7) and was called ery-throidine. This name had already been used by Altamirano referring, however, to the unknown constituents of the plant (774). Further analytical investigations revealed the material isolated to be a mixture of isomeric alkaloids, which were subsequently named a- and /3-erythroidines (14 and 225, see Figs. 2 and 4). 

J.I. Seeman, H.V. Secor, D.W. Armstrong, K.D. Ward and T.J Ward, Separation of Homologous and Isomeric Alkaloids Related to Nicotine on a P-cyclodextrin-bonded Phase, J. Chromatogr., 483... 

The most important Chinchona alkaloids are quinoline derivatives. The quinoline nucleus of these compounds is linked at position 4 via a secondary alcoholic group to the so-called quinuclidine nucleus, a system of two piperidine rings with a common nitrogen atom and three common C-atoms. A number of differently substituted and isomeric alkaloids exist. Of special importance are the alkaloids quinine and quinidine. 

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