Sedum alkaloids

Piperidine alkaloids Lupin alkaloids Sedum alkaloids NPAAs... 

Lysine-Derived Alkaloids. Just as putresciae (36) derived from ornithine (23) is coasidered the pregenitor of the aucleus fouad ia pyrrolidine-containing alkaloids, so cadavetiae [462-94-2] (44), C H 4N2, derived from lysiae (24) is the idealized pregenitor of the 1-dehydropiperidine [28299-36-7] nucleus (45), C H N, found in the pomegranate, Sedum Dobelia, Dupin, and Lycopodium alkaloids (39). 

In addition to lupines, poison-hemlock and Nicotiana spp., other plant species of the genera Genista, Prosopis, Lobelia, Cytisus, Sophora, Pinus, Punica, Duboisia, Sedum, Withania, Carica, Hydrangea, Dichroa, Cassia, Ammondendron, Liparia, and Colidium contain potentially toxic and teratogenic piperidine alkaloids. Many plant species or varieties from these genera may be included in animal and human diets (Keeler and Crowe, 1984). 

Alkaloids have been found in a few species. In this survey, 81 samples of 64 species were tested to give, as the only positive, the known Bryophyllum daigremoniianum. Crassula expansa, C. mariti-ma (1/2), Crassula sp. cf. cotymbosa, C. vagitana (1/3), Echeveria pubescens, Sedum oxypetalum, and Sedum sp. (1/5), which were not known, were also positive. 

The syntheses of sedum and related alkaloids using isoxazolidines as key intermediates have been reviewed <02T5957>. 

The structure of (—)-sedinine, an alkaloid of several Sedum spp., must be modified to (12), with the double-bond at C(3)-C(4) rather than at C(4)-C(5), as a consequence of X-ray diffraction analyses of the base and of its hydrochloride (12) also represents its absolute configuration.18 Sedacryptine is a new minor base from S. acre a single-crystal X-ray analysis of the free base points to structure and relative stereochemistry (13).19 The alkaloid could be identical with hydroxy-sedinone , isolated earlier.20... 

Pyridine and piperidine strategies of syntheses of the Sedum and related alkaloids 02T5957. 

An X-ray diffraction analysis of (-)-sedinine, an alkaloid present in several Sedum species, esteiblishes the position of the double bond in the heterocycle at rather than at A as had been suggested earlier. The structure (22) for the alkaloid represents its absolute stereochemistry (C. Hootele et al.. Tetrahedron Letters, 1980, 21, 5063), and the ( )-form has now been synthesised (M. Ogawa and M. Natsume, Heterocycle, 1985, 23, 831). Sedacryptine, isolated from S. acre, has the relative stereochemistry indicated in formula (23) (Hootele et al, Tetrahedron Letters, 1980, 21, 5051) and its racemate has also been synthesised (A.P. Kozikowski and R.J. Schmiesing, J.org.Chem., 1983, 48, lOOO M Ogawa and M. Natsume, Heterocycles, 1985, 23, 831). 

N-Methylpelletierine.— Labelling of 7V-methylpelietierine (13) by [6- C]-dl-lysine in Sedum sarmentosum has been shown to be confined to C-6 and thus the piperidine ring of this alkaloid, like anabasine (14), is derived from lysine by way of unsymmetrical intermediates, and cadaverine cannot be a true precursor. In confirmation of the role of this amino-acid, [4,5- H2,6- C]-DL-lysine was incorporated into iV-methylpelletierine without alteration of the ratio. 

Many 2-substituted piperidine alkaloids are produced by Sedum. In one study, for example, TLC and GC/MS were used, to survey alkaloids in sixteen Sedum species. The alkaloids reported were sedridine (167), /V-methylsedridine (168), pelletierine (169), N-methylpelletierine (170), 4-hydroxysedamine (172), norsedamine (177), allosedamine (178), 3-hydroxyallosedamine (175), as well as the 2,6-disubstituted piperidines sedacrine (231), sedinine (236), and sedinone (232) [426]. 

Hydroxysedamine (172) and (+)-4-hydroxyallosedamine (173) were isolated from Sedum acre using countercurrent distribution and preparative chromatography [448]. Their structures were determined using MS, and 13c NMR of 172, 173, and their diacetyl derivatives, and by synthesis via tetrahydro 1,3-oxazines of known absolute configuration. Conversion of these oxazines to 172 and 173 via a UAIH4 reduction established the absolute configuration of the new alkaloids [448],... 

Sedacrine (231) and sedinone (232), along with 236 and a number of other Sedum alkaloids, were investigated by H and 13c NMR to determine their preferred solution conformations [509]. Both 231 and 232 were synthesized using anodic oxidation to functionalize and allow for the addition of the side chains as a key step [510]. 

Further work56 has now disproved this pathway, at least for sedamine. When [2-3H,6-14C]lysine was administered to Sedum acre the alkaloid incorporated both labels with an unchanged isotopic ratio. Thus, the hydrogen at C(2) of lysine is not lost in the biosynthesis as would be required for pathway a. An alternative sequence, path b (Scheme 16) satisfactorily accommodates the fresh evidence. Decarboxylation at C-2 now precedes rather than follows the oxidation step. To avoid the generation of a symmetrical diamine, the amino-group at C(6) is differentiated by methylation in the first step. 

Two species of Sedum have been examined for alkaloids, i.e., Sedum acre L. and Sedum sarmentomm Bunge. The first yielded the alkaloids sedamine (83) and sedridine (84, 85), whereas the other contained IV-methyl isopelletierine and its dihydro derivative (86). 

In light of current knowledge on the biosynthesis of Sedum and other piperidine alkaloids, one can surmise that the piperidine and piperideine moieties of the amides are, in fact, both probably produced from pyridoxal-bound L-lysine and cadaverine, a pathway proposed and elegantly elucidated by Leistner and Spenser in the early 1970 s (cf. [13]). In a similar manner, biosynthesis from omithine/putrescine could produce the pyrrolidine ring found in many of the Piper amides. On the other hand. 

The conversion of lysine into piperidine alkaloids involves retention of hydrogen isotope at C-2/° The sequence is suggested to be that shown in Scheme 1, and catalysis of the reaction may be attributed to L-lysine decarboxylase. This enzyme, from the micro-organism Bacillus cadaveris, has been found to carry out the conversion of L-lysine into cadaverine with retention of configuration. Decarboxylation of L-[2- H]lysine by this enzyme then affords [15- H]-cadaverine. When this material is converted into alkaloids, e.g. iV-methyl-pelletierine (4 R = Me), the tritium attached to what becomes C-2 is lost cf. refs. 5 and 6. On the other hand, conversion of lysine into sedamine (27) in Sedum acre results in retention of the tritium originally present at C-2. The simplest explanation is that protonation of (26) in the micro-organism and plant proceeds with opposite stereochemistry. This is at variance, however, with current ideas on the stereochemistry of reactions that are catalysed by pyridoxal phosphate. ... 

Sedum alcaloids. C-2 monosubstituted piperidine alkaloids from Sedum species (Crassulaceae). Seda-mine is responsible for the hot taste of the wall pepper (Sedum acre). 

---