Alkaloids from Other Sources

While 1- and 2-oxygenated tricyclic carbazole alkaloids were isolated primarily from higher plants, various tricyclic carbazole alkaloids, which are 3-oxygenated or 3,4-dioxygenated, were obtained from alternative natural sources, such as microbial, marine, and mammalian sources. 

Tricyclic Carbazole Alkaloids 1 3-Oxygenated Tricyclic Carbazole Alkaloids 

Since the late 1960s, several carbazole alkaloids oxygenated in the 3-position were isolated from diverse natural sources, the majority of which were isolated from different plant sources. However, in 1979, Moore et al. reported the isolation of two unusual, non-basic, 3-oxygenated carbazole alkaloids, hyellazole (245) and chloro-hyellazole (246), from the blue-green marine algae Hyella caespitosa (225). These alkaloids have structures entirely different from those of the carbazole alkaloids isolated from terrestrial plants. 

The UV 220, 235, 242, 255 (sh), 272 (sh), 300 (sh), 310, 348, and 360 nm] spectrum of chlorohyellazole (246) resembled that of hyellazole (245). The H-NMR spectrum was also similar to that of hyellazole (245), except for the absence of H-6, as shown by two, mutually mete-coupled protons at 8.13 and 7.27, assigned to a deshielded H-5 and H-7, respectively, indicating the position of the chlorine atom to be at C-6. These spectral data led to structure 246 for chlorohyellazole. This assignment was unequivocally confirmed by an X-ray crystal structure analysis 

In 1989, Kato et al. reported the isolation of carazostatin (247) from Streptomyces chromofuscus. Carazostatin represents a novel radical scavenger more active than butylated hydroxytoluene (BHT) (226). Moreover, it exhibits strong inhibitory activity against the free radical-induced, lipid peroxidation in liposomal membranes, and shows stronger antioxidant activity than ot-tocopherol (227). 

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QUINOLIZIDINE ALKALOIDS FROM OTHER SOURCES -LUPINE ALKALOIDS... 

Alkaloids from other Sources.—Ergotin—C10H1SIT2O3—and Eo-holin are two brown, amorphous, faintly bitter, and alkaline alkaloids obtained from ergot. They are readily soluble in water and form amorphous salts. The medicinal preparations known as ergotin are not the pure alkaloid. 

The natural sources of carbazole alkaloids are listed in Table 2.1. Carbazole and various alkylcarbazoles have also been obtained from other sources, such as coal tar, petroleum oil, soil humus, the polluted atmosphere of industrial areas, as well as cigarette smoke. 

Biogenetic considerations of the carbazole alkaloids isolated from other sources have led to a different view about the genesis of these alkaloids. Without exception, to date, all of the biogenetic proposals of the carbazole alkaloids isolated from other sources have indicated L-tryptophan has a progenitor. 

Many other natural products contain terpenoid elements in their molecules, in combination with carbon skeletons derived from other sources, such as the acetate and shikimate pathways. Many alkaloids, phenolics, and vitamins discussed in other chapters are examples of this. A particularly common terpenoid fragment in such cases is a... 

Since the last review on ergot alkaloids, important new alkaloids from different sources, mostly from new ergot strains, have been discovered. Their proposed structure could in some cases be confirmed by synthesis. Some of them seem to be intermediates in the biogenetic pathway from tryptophan to the peptide alkaloids. Others are considered as end products of secondary plant metabolism. In any case we find many interesting structures among these recently discovered substances. 

The major bases found in nucleic acids are adenine and guanine (purines) and uracil, cytosine, and thymine (pyrimidines). Thymine is found primarily in DNA, uracil in RNA, and the others in both DNA and RNA. Their structures, along with their chemical parent compounds, purine and pyrimidine, are shown in Figure 10.1, which also indicates other biologically important purines that are not components of nucleic acids. Hypoxanthine, orotic acid, and xanthine are biosynthetic and/or degradation intermediates of purine and pyrimidine bases, whereas xanthine derivatives—caffeine, theophylline, and theobromine—are alkaloids from plant sources. Caffeine is a component of coffee beans and tea, and its effects on metabolism are mentioned in Chapter 16. Theophylline is found in tea and is used therapeutically in asthma, because it is a smooth muscle relaxant. Theobromine is found in chocolate. It is a diuretic, heart stimulant, and vasodilator. 

Occurence and New Alkaloids.—Six acridone alkaloids have been isolated from the leaves of Bauerella simplicifolia subsp. neo-scotica. Four of the alkaloids, i.e. melicopine (27), melicopidine (28 R = Me), 1,3-dimethoxy-JV-methylacridone (29 R1 = Me, R2 — H), and xanthovodine (28 R = H), have been obtained from other sources, but the alkaloids (29 R1 = H, R2 = OMe) and (29 R1 — R2 = H) were known previously only as synthetic compounds. The new alkaloids were identified by spectroscopy, by chemical correlation, and by synthesis. 

Keeler RF, Binns W. Teratogenic compounds of Veratrum californicum (Durand). V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources. Teratology. 1968 1(1) 5-10. 

Phytochem., 1980, 19, 718). This last compound has previously been isolated from other sources, its stereochemistry has been deduced by chemical correlation with alkaloids of known structure (T. Ravao et al.. Tetrahedron Letters, 1985, 26, 837). 

The alkaloid edulinine was first obtained from Casimiroa edulis Llave and Lex., and it was assigned the diol structure 54 on the basis of NMR and mass spectra (17). An optical rotation was not recorded, but the alkaloid from this source was later described as being optically active, [a]D-15° (47). The constitution was confirmed by comparison with ( )-edulinine obtained from synthetic Af-methylplatydesminium iodide by treatment with aqueous ammonia at 20° (37) and with (-)-edulinine, [a]D-20° (CHC13), resulting from a similar reaction on (+)-7V-methylplatydesminium salt (37). The alkaloid has been obtained from a number of other sources ... 

From the comments set forth above, it is obvious that the characteristics of the cinchona alkaloids must be the primary subject for the present discussion. Only brief reference will be made to alkaloids derived from other sources, inasmuch as none of these has been of sufficient interest to justify more than cursory study at the therapeutic level. 

Numerous bisindole alkaloids, formed by dimerization of monomeric monoterpenoid-derived indoles, have been isolated. Probably the best source of these alkaloids is Cathara-nthus roseus bisindole alkaloids from this source have been tabulated (Blasko and Cordell, 1990). Several of these alkaloids antitumor activity (Blasko and Cordell, 1988) most important in this regard are vincristine (55) and vinblastine (56) from Catharanthus roseus (Fig. 34.15). Certain other dimeric indole alkaloids known as curares have paralytic effects in animals (see the subsection Curares from Strychnos species, above). 

Related alkaloids have been obtained from other sources Lunasia amara, Ptelea trifoliata, Orixa japonica, Skimmia japonica, etc. 

Like plasma and urine, matrixes from plant or environmental sources contain a vast diversity of components. Thus, achiral-chiral LC-LC is also useful for analysis involving samples from these sources. Stalcup et al. (1991) studied the enantiomeric purity of scopolamine extracted from Datura sanguinea in both homogenized plant leaves and commercial extracts. A reverse-phase separation on a C j g column separated the scopolamine from other alkaloid and matrix components while the enantiomeric separation (also in the reverse-phase mode) was carried out on two coupled [3-cyclodextrin columns or a single acetylated (3-cyclodextrin column. The single... 

NPR191>. Periodical reports on other types of alkaloids from the same sources also contain information on certain arenoquinolizine alkaloids like the berberin and emetan derivatives that are normally classified as isoquinoline alkaloids. For surveys of the literature published prior to 1996, perusal of the corresponding chapters in previous editions of this work <1984CHEC(2)525, 1996CHEC-II(8)507> is recommended. 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

With the advent of modern techniques, instrumentation and automation in isolation and structural characterization, numerous antidiabetic compounds have been isolated, purified and identified from different natural sources, especially medicinal plants. This part summarizes promising natural chemical entities with diverse structures reported for their therapeutic activities against diabetes. These compounds are broadly categorized into alkaloids, terpenoids, flavonoids, and phenolics, including compounds from other groups. 

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