The Alkamines

The known alkamines isolated directly from plant material, obtained by acid or enzymatic hydrolysis of naturally occurring glycosides or prepared by microbiological hydroxylation, are summarized in Table III. The related compounds obtained only by synthesis are not included in this table. 

7a-Hydroxytomatidine (XIX) 7j8-Hydroxysolasodine (XX) 7)3-H3 droxysoladulcidine (XXI) Ox-Hj droxj tomatidine (XXII) Oa-Hj droxj solasodine (XXIII) 

15a-Hvdroxysolasodine (XXVIII) 15 -Hydroxysolasodine (XXIX) l-Sa-Hj droxysoladulcidine (XXX) 15jS-Hydroxysoladulcldino (XXXI) 15-Oxosoladulcidine (XXXII) ( )  

l la-Ditiydroxj-toniatidino (XXXIII) 7f,lla-Dih droxj solasodine (XXXIV) ( ) 

Direct isolation Hydrol. of a glycoside Hyxlrol. of a glycoside H drol. of glycosides Hy drol. of glycosides 

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Stereoisomerism in either the alkamine nucleus or the acyl residue has a considerable effect on the pharmacological action of the tropeines and cocaines. Differences in activity of tropine and i/i-tropine and their benzoyl derivatives have been mentioned already, and there seems to be a consensus of opinion that the i/i-cocaines (alkyl- or aryl- acyl esters of 0-ecgonine) are less toxic and more potent local anfesthetics than the corresponding cocaines, derived from 1-ecgonine. ... 

Poethke shows that on alkaline hydrolysis protoveratrine yields acetic, Z-methylethylacetic and methylethylglycollic acids and the alkamine protoverine. It is therefore a triacyl ester of protoverine. 

XXX) by reduction to XXXII and subsequent acetobromolysis, and this product was converted into the ( —)-diol XXXI, identical with the alkamine of natural valeroidine (III). Inversely, partial methylation 39b) of that diol gave the methiodide (XXXIII) of (— )-6(8-methoxy-tropine so that no breaking of the C-6—0 bond occurred during demethy-lation hence, the methoxyl and hydroxyl groups are both The degradation by nitric acid of the (+ )-2,4-dioximino-3-tropanone (39 a,b) furnished 25% of [Pg.280]

Delectine.—A new diterpenoid alkaloid, delectine, has been isolated from Delphinium dictyocarpum7 This base, C31H44N2O8, m.p. 107—109 C, was shown to be the anthranilate ester (6) by chemical and spectral studies and by conversion into 00 -dimethyl-lycotonine (7). Acetylation of delectine gave an NO-diacetyl derivative (8). On alkaline hydrolysis of delectine, anthranilic acid and the alkamine (9) were obtained. Methylation of (9) with methyl iodide-sodium hydride gave (7), which was... 

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. 

The stereochemistry of teloidine, the alkamine of meteloidine, has been elucidated as far as the vicinal hydroxy groups are concerned by its Robinson synthesis from cis-dihydroxysuccinic dialdehyde (68). Their relative positions to the nitrogen, however, have been revealed only by... 

A. majimai Nakai and A. japonicurn and is a benzoate of the alkamine, isohypognavinol (CCXXXVIIa) (70, 92). The latter has three acylatable... 

Despite the fact that the reaction mechanism, by which the ester bond between the alkamine and the acid moiety is formed, is still not fully understood, it has been recently reported [38] that a number of esters can be formed in vitro by acyltransferase reactions involving the transfer of the acidic group from the relevant coenzyme A to tropine or pseudotropine. Thus, tigloyl-CoA pseudotropine acyl transferase, which esterifies the 3P-hydroxy group of pseudotropine with tigloyl-CoA to give 3(3-tigloyloxytropane has been isolated from hairy root cultures of Datura stramonium and characterized [39]. 

Two alkaloids, lindelofine, C16H27O4N (m.p. 106-107°, [a] +50° picrate, m.p. 123-124° picrolonate, m.p. 134-135°), and lindelofamine, C20H33OBN (m.p. 88°), were obtained from this plant. Alkaline hydrolysis of lindelofine yielded an alkamine, CgHuON (m.p. 40-41°), which was shown to be identical with d-isoretronecanol, and trachelanthic acid. Similarly, alkaline hydrolysis of lindelofamine yielded the same alkamine and a mixture of trachelanthic and tiglic acids. It is suggested that trachelanthic acid is bound to the alkamine and that the tiglic acid esterifies one of the hydroxyls of the former (129). 

Many Solanum species contain alkaloidal glycosides which on removal of the sugar residue by hydrolysis yield alkamines with 27 carbon atoms. A number of the same alkamines have been also isolated along with their glycosides, but since no particular precautions to prevent enzymatic hydrolyses have been taken, it is not always certain that the alkamines are primary plant constituents. The alkamine solanocapsine has only been found as such, and it has not been possible to isolate its glycoside even under conditions designed to circumvent its hydrolysis. 

In the above three formulas the group R represents the alkamine component. The order of attachment of the monosaccharide components was determined by partial and progressive hydrolysis. The pyranose type and the position of coupling of the sugars was determined from the periodic acid oxidation, but the complete structures are not known with certainty. 

On hydrolysis with methanolic potash protoveratridine yields the alkamine germine, C27H430gN, and d-(—)-a-methylbutyric acid, [ ]d — 23.1° (water) (51). 

Alkaline hydrolysis of germerine yields the alkamine germine, D-(—)-o-methylbutyric acid, [ ]d — 22°, —25 (water), and (-l-)-o-hydroxy-a-methylbutyric acid, m.p. 72-73°, [a]o + 4.4° (water). With baryta at 40° it yields protoveratridine on partial hydrolysis and ultimately germine (19, 51). 

Stoll and Seebeck (60b) have reported the isolation of an alkaloid, CaiHeiOisN, m.p. 181-183°, [a]o — 11.7° (pyridine), -t-5.4° (chloroform) from V. album. For it they have proposed the name veralbidine. A thiocyanate, m.p. 235-236°, and a hydrochloride, m.p. 250-251°, are described, but neither the nature of the alkamine nor that of the sugar or acid or both has been reported. 

The most significant chemical progress in the last decade has been the isolation and structural elucidation of an increasing number of new steroidal alkamines and glycosides the structures of which, however, still belong to one of the known types 1-5. Extensive work has also been directed to a number of new partial and total syntheses as well as to the degradation of the alkamines, particularly to pregnane derivatives. A number of review articles have been published in the last years (e.g., 31-38). 

The alkamines isolated directly from plant material or obtained by acid or enzymatic hydrolysis of naturally occurring glycosides between 1967 and 1979 are summarized in Table III. Physical me ods are of increasing importance in structure elucidation. Recent papers have dealt with IR spectra (173), H NMR (174,175), NMR (176-178,357,358), EPR (179), ORD (180-183), and MS (184,351,352) of Solanum alkamines. Some X-ray analyses have been carried out since 1967 (58, 81, 149, 185-189, 359). Tables rV-VI survey the characteristic features of H NMR, NMR, and MS of Solanum alkaloids. Silver nitrate-containing adsorption layers were shown to be useful in TLC separation of 5a-saturated and S-unsaturated alkamines (194,195). High-pressure liquid chromatography has been applied successfully for the separation of steroidal Solanum and Veratrum alkamines (373). 

The quaternary derivatives, not having lone pair electrons attached to the quinuclidine nitrogen to interact with electrophilic centres of the corresponding receptors, are thus compounds of lower pharmacological activity. Experimental data produced in the comparative study of the ganglionblocking action of the bisquatemary derivatives of the alkamine esters of quinuclidinecarboxylic- and 1,6-dimethylpiperidinecarboxylic acids lends sup-... 

In contrast to the alkamines/glycoalkaloids (Sect. 7.8.) their Af-liree homologues could be detected already in basal branches of the family tree, i.e., certain members of the Schwenckioideae and Petunioideae. 

Table 7.3 Steroidal alkaloids (alkamines) alphabetically listed within the different structural types For 41 out of altogether 115 compounds from Solarium spp. (113 compounds), Lycianthes biflora, and Saracha punctata (one compound each) at least one corresponding glycoalktiloid was found and structurally elucidated, i.e., for 36% of the alkamines also corresponding glycosides are known (continued)...

Epiminocholest-22 N)-ene Skeleton. Cyclic azomethines of the structural type CXXXI have been obtained, as mentioned above, by isolation from plant materials (see tomatillidine, verazine, the alkamines from S. congestiflorum), by acetylation of spirosolanes under strong acidic conditions 265, 271, 272), leading to 16)3-acetoxy substituted derivatives, by alkaline treatment of the V-chloro derivatives of 16-unsubstituted 282,286) and 16a-hydroxylated 254,255) 22,26-epimino-cholestanes, as well as by photolytic decomposition of the iV-nitroso-0,0-diacetate LXXXIX which gave the azomethine diacetate XCII 256, 257). 

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