Tropane group alkaloids

Tritopine. See Laudanidine. Tropacocaine, 62, 64, 79, 100 pharmacological action, 106 Tropane, 87, 108 Tropane group alkaloids, 64, 776 pharmacological action, 105 Tropeines, 73, 79, 81 Tropehone, 80 Tropic acid, 72... 

Tropane Group. SolanaceOus Alkaloids, Convolvine and Allied Alkaloids, Dioscorine, Alkaloids of Coca Leaves (Erythroxylon coca). ... 

N. tfibacuTn of nomicotine in N. glutinosa and of anabasine in N. glauca. In the tropane group, i-hyoscyamine predominates in A. belladonna and f-hyoscine in Datura metel L. (68). The distribution of the alkaloids in a graft whose stock and scion produce different kinds may thus prove illuminating. 

Results of some of the grafting experiments described in the previous section sug t strongly that alkaloids, in particular those of the.nicotine and tropane groups, are carried from the root and distributed throughout the aerial parts of the plant. The obvious agent of transport is the transpiration stream, and its participation has been confirmed by Dawson s (82) observations on the sap bleeding from cut stumps of Connecticut tobacco plants. The sap could be seen to exude from the xylem only and contained... 

Duboisia. Interesting observations have been made on the alkaloids of the Duboisias in recent years. Duboisia myoporoides contains alkaloids of the tropane group. It has a wide geographical range in Eastern Australia... 

The alkaloids of the tropane group show a series of common chemical characteristics, particularly that of being esters of organic acids combined with bicyclic hydramines. They include Z-hyoscyamine and its isomer atropine, cocaine, scopolamine or hyoscine, and a series of secondary alkaloids. 

Similar results have been published for other Solanaceae alkaloids, namely, those of the tropane group. Heine (1942) grafted Datura scions upon Nicotiana rustica and found that nicotine accumulated instead of tropane alkaloids. This finding was confirmed by Hills et al, (1946) with Nicotiana-Duboisia grafts. The tobacco scion on Duboisia root was found to accumulate tropane alkaloids. Surprisingly, the tobacco scion accumulated both hyoscine and the unesterified tropine. In all grafts between plants... 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

The tropane alkaloids are a well-recognized group of structurally related natural products. Long before elucidation of the structures, the mydriatic and anesthetic action of several compounds was exploited (6). The very extensive literature covering the pharmacological properties of the tropane alkaloids will be considered only briefly in this chapter. Readers with a deeper interest in the subject are referred to other publications (7-14) and to the references given in Section VII. 

It has been confirmed that isoleucine but not 3-hydroxy-2-methylbutanoic acid is a precursor for the tiglic acid which is the esterifying acid in some tropane alkaloids [e.g., meteloidine (77) (735)]. In the biosynthesis of meteloidine (77) from 3a-hydroxytropane (1), the hydroxyl groups at C-6 and C-7 are most probably introduced after esterification at C-3 (5) (Scheme 23). In this connection we would point out that scopolamine (89) is a well-known 2,3) metabolite of hyoscyamine (27) and that the reaction proceeds via 6-hydroxyhyoscyamine [(—)-anisodamine (63)] and 6,7-dehydrohyoscyamine (211) (Scheme 26). 

These are the group of alkaloids that possess a 8-methyl-8-aza-hicyclo [l,2,3]octane or tropane skeleton, e.g. atropine, cocaine and scopolamine. Tropane alkaloids occur mainly in plants from the families Solanaceae and Erythroxylaceae. 8-Aza-hicyclo[l,2,3]octane, i.e. tropane without the 8-methyl group, is known as nortropane. 

The a-methoxylated derivatives are shown to be versatile synthons because of the reactivity of the methoxy group near the nitrogen atom, a-Methoxycarbamates, prepared by anodic oxidation, were used as key intermediates in the synthesis of a-amino acids,200 a new carbon-phosphorus bond-forming reaction,200 and in a new method of acylation of aliphatic amines at the -position.201 The application of this reaction to the synthesis of pyrrolidine, piperidine, and tropane alkaloids is also described.202... 

The alkaloids of this group are derived from a combination of a piperidine and a pyrrolidine ring, designated as tropane (Figure 14.2). The 3-hydroxy derivative of tropane is known as tropine and is the basic component of atropine. When atropine is hydrolyzed, it forms tropine and tropic acid (a-phenyl-p-hydroxy-propionic acid). Atropine is the tropic acid ester of tropine. It has been prepared synthetically. Tropic acid contains an asymmetric carbon atom. The racemic compound (atropine) as obtained naturally or as synthesized may be resolved into its optically active components, d- and /-hyoscyamine. Atropine is racemic hyoscyamine that is, it consists of equal parts of /-hyscyamine and plant cells and also in the process of extraction, so that the relative proportion of the isomers in the plants and in the preparations varies. However, atropine itself does exist in small amounts in the plants, although most of it is formed from the /-hyoscyamine in the process of extraction. 

In contrast to the observation of the French group that rat liver microsomes did not possess an esterase capable of hydrolyzing tropane alkaloid... 

Tropane Alkaloids.—It is known that tropine (26) is a precursor for meteloidine (27),42 and its close relative hyoscyamine (29) is a precursor for scopolamine (28).43 Experiments with samples of (26) labelled with /3-tritium at C-6 and C-7 show that entry of the two /S-hydroxy-groups in (27) must occur with normal retention of configuration since almost complete loss of tritium occurred.44 Tritium was again lost almost completely on formation of scopolamine (28). On the assumption that early conclusions45 on the sequential intermediacy of (30) and (31) in the biosynthesis of (28) are correct, formation of (30) involves normal retention of configuration (loss of half the tritium) and cis-dehydration then occurs to give (31) (loss of remaining tritium). [In these experiments the hyoscyamine (29) isolated showed appropriately no loss of tritium.]44... 

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