The Ester Alkaloids

Re-examination of the alkaloids of Heliotropium europaeum has revealed the presence of a new alkaloid, acetyllasiocarpine (17) as a minor component. The alkaloid could not be crystallized, but gave lasiocarpine (18) on partial hydrolysis. Proof that the acetoxy group was attached to C-3 was obtained from the C n.m.r. spectrum, which showed a downfield acylation shift of approximately 12 p.p.m. for C-3 by comparison with the corresponding signal in the spectrum of lasiocarpine (18). Acetyllasiocarpine (17) was regenerated from lasiocarpine (18) by acetylation with acetic anhydride. 

Pedersen has examined the pyrrolizidine alkaloid content of 19 Danish species of the Boraginaceae. The isolated alkaloids from ten of these species were purified by preparative thin-layer chromatography and investigated by mass spectrometry. The 

In last year s report the occurrence of a new alkaloid, crotalarine (30), from Crotalaria burhia Buch.-Ham., was reported. Atal et al ° have also reported the presence in this species of an alkaloid, croburhine, which is clearly identical with crotalarine (30). The observation that monocrotaline (31) also occurs in C. burhia 

There are four stereoisomers of 3-hydroxy-2,3,4-trimethylglutaric add [(35)— (37)]. The two meso forms, fulvinic (35) and crispatic (36) adds are the esterifying adds of the alkaloids fulvine and crispatine respectively. Now the two remaining 

The mode of attachment of the necic acid in crotastriatine (from Crotalaria striata) to the nedne (retronedne) has been investigated. Hydrogenolysis of crotastriatine gave a product, presumably the zwitterion (41) the i.r. spectrum of which indicated the presence of an intact a/S-unsaturated ester function, confirming the mode of attachment as in (40). Crotastriatine (40) is the acetate of nilgirine (42) which has also been found in Crotalaria striata (= C. mucronata). Acetylation of nilgirine (42) with acetic anhydride-perchloric acid gave crotastriatine (40). 

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The sugar alkaloid colchicoside and its synthetic sulfur analog thiocol-chicoside were acylated with esters of trifluoroethanol and with isopro-penylacetate in pyridine in the presence of the enzyme subtilisin from Bacillus subtilis (132). The 13C-NMR spectra of the ester alkaloids, which... 

Aspidofractinine (146), the parent member of this third large subgroup of alkaloids of the aspidospermine group, does not occur widely, and the only recent report of its occurrence is in the stem bark and root bark of Hunteria elliottii Pichon (12). Its Na-methyl (147) and Na-methyl-14,15-didehydro (148) derivatives are new alkaloids, which have been found in the roots of Vinca sardoa (67). The ester alkaloids occur much more widely, and several new sources have been reported for (—)-kopsinine (149), (-)-venalstonine (150), (-)-venalstonidine (151), and several minor alkaloids (152-160) (Table I). Of the six reported isolations of 15a-hydroxykopsinine (154), one (16) does not spedfy the configuration of the hydroxyl group. Since it is described as a known alkaloid, it is presumed to be 15a-hydroxykopsinine, because 15/3-hydroxykopsinine is unknown as a natural product. 

The acid components required for the synthesis of the ester alkaloids, (+)-trachelanthic and viridifloric acids, were synthesised by stereospecific routes, since the relative stereochemistry of the asymmetric centres in these acids was still uncertain. Eventually they were obtained by appropriate stereospecific icis or trans) hydroxylation of trans-2-isopropylcrotonic acid (34), and its cis-isomer obtained by photochemical isomerisation. After resolution, (+)-trachelanthic acid was identified as the t/irco-2-isopropyl-2,3-dihydroxybutyric acid (35) the corresponding erythro-isomet was identified as viridifloric acid. 

The ester alkaloids were then synthesised by base-catalysed transesterification of the methyl ester di-O-benzyl ether of the appropriate hydroxyacid with the appropriate 1-hydroxymethylpyrrolizidine, followed by debenzylation of the product by palladium-catalysed hydrogenolysis. In this way the synthesis of trachelanthamine (36), its diastereoisomer viridiflorine (37), and lindelofine... 

Veratrum alkaloids are produced by lilaceous plants of the suborder Melanthaceae of which Veratrum album, the hellebore of Europe and northern Asia, Veratrum viride, the swamp hellebore or Indian poke of North America, and Schoenocaulon officinale of Central and South America are the best known. The latter yields the sabadilla seed which was used as an insecticide by Indians in pre-Columbian times (Crosby 1971). The alkaloid fraction of the seeds, often termed veratrine, is a poorly defined mixture mostly of the ester alkaloids, veratridine, and cevadine and of the alkamine veracevine or its isomer cevine. 

Mixture of the alkaloids of Veratrum viride, alkavervir, Veriloid. Partially purified prepn of the ester alkaloids, Vogitryi. 

The interpretation should find the explanation of the following facts 1. The coupling reaction with biogenic amines is selective, if it is at all, in favour of the 3R or 1R epimer (R series), and the selectivity could be increased (especially in the vincoside series) by increasing the bulkiness of the ligand attached to N-4 (or N-2). 2. The A -benzyl oxotryptamine derivative gave the ester (35-78b) as main product, the oxotryptamine derivative the (3R-19) lactam. 3. The lactamization of the ester alkaloids is much faster in the R series, than in the S series. 4. The neo compounds are formed in smaller amount than the normal products. 

Tropane Alkaloids.—Previous research had shown that the tiglic acid (55) moieties of the ester alkaloids of Datura species, e.g. (56), (57), and meteloidine (58), arise specifically from L-isoleucine (52). " This amino-acid is also a source for angelic acid (the geometric isomer of tiglic acid) in Cynoglossum officinale and it is degraded in animal tissues to tiglic acid, probably by way of 2-keto-3-... 

The structure of the ester alkaloid, schizophylUne followed from its facile conversion (chromatography over activity I alumina) into isoschizogaline 42). 

The benzene extracts of a crude alkaloid mixture contain the alka-mines as well as the ester-alkaloids. The former are largely eliminated by crystallization and the amorphous ester-alkaloid mixture is acetylated and extracted with 5% tartaric acid. The resultant extracts, mostly... 

Sample preparation methods without any loss of the target compounds are important, especially when a quantitative assessment of all alkaloids in a given plant sample is required. Eor many alkaloids, the sample preparation procedure is based on the difference in the solubility of the alkaloids salt in comparison with the free bases. An acidic aqueous extraction must be basified to transfer alkaloids into the free base for extracting into organic solvents nonmiscible with water. Excessive use of alkali, however, is detrimental for the ester alkaloids. 

The phenylquinolizidine alkaloids lasubine I and lasubine II were obtained from the leaves of Lagerstroemia subcostata as major alkaloids, together with the ester alkaloids subcosine I and subcosine II. These alkaloids are considered to be intermediates in the biogenetic route of the lactonic alkaloids. Thus, lysine, phenylalanine, and a C2 unit (acetate) produce the phenylquinolizidine alkaloids. These are then esterified with another phenylalanine unit to the ester alkaloids, followed by conversion to the lactonic alkaloids by oxidative coupling. 

Phenylalanine as a Precursor.— Tropic acid is found in Nature as the add moiety of the ester alkaloids hyoscyamine and hyosdne. A large amount of information, some conflicting, has been published in the past decade on the origin of this relatively simple molecule. We will review these data critically in the hope that it will aid work on the currently unsolved problem of its biosynthesis. It was discovered in 1960 that the administration of [3- C]phenylalanine to intact Datura stramonium plants yielded tropic acid having essentially all its activity at C-2. Later workers confirmed this result in D. stramonium (intact plants) and D. metel (sterile root cultures). It was then established that the other carbons of the phenylalanine side-chain were used for the production of the side-chain of tropic acid. The pattern of labelling found in the tropic... 

Activity was found in these necine bases, which were obtained by hydrolysis of the ester alkaloids found in this species. Labelled material was obtained with Intact plants, and de-rooted ones, indicating that the roots are not necessary for the formation of these pyrrolizidine bases. The specific activity of the trachelanthamidine was, in general, higher than the other two bases, consistent with the biosynthetic pathway ... 

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