Proto alkaloids

The possible therapeutic applications of these alkaloids as proto-zooicidal agents, coronary dilators and ecbolics, and in nervous diseases, for example in the treatment of post-encephalitic conditions, have been discussed by a number of authors. The alkylharmols, referred to above, form part of an extensive series prepared by Coulthard, Levene and Pyman, and tested by these authors for bactericidal properties and by... 

On treatment of N-methylpapaverine, formed by the lithium aluminum hydride reduction of papaverine methiodide with phosphoric acid, N-methylpavine is formed which is identical with the racemic alkaloid argemonine. This reaction was used for the synthesis of the alkaloid (-h)-coreximine (268) (174) and similar compounds containing the proto-berberine grouping in the molecule (269,270). 

Indenobenzazepines have been used as key intermediates for synthesis of rhoeadine, protopine, phthalideisoquinoline, and spirobenzylisoquinoline alkaloids. Several new alkaloids possessing an indenobenzazepine skeleton have been isolated, and they are presumably biosynthesized from proto-berberine alkaloids. 

The precursors of true alkaloids and protoalkaloids are aminoacids (both their precursors and postcursors), while transamination reactions precede pseudoalkaloids (Tables 1 and 10). It is not difficult to see that from all aminoacids only a small part is known as alkaloid precursors (Table 19). Both true and proto alkaloids are synthesized mainly from the aromatic amino acids, phenylalanine, tyrosine (isoquinoline alkaloids) and tryptophan (indole alkaloids). Lysine is the... 

So-called proto- and pseudoalkaloids are known throughout the family and several reviews of these have appeared. Some of the species were assayed here and likewise found to be alkaloid-positive Capsella hursa-pastoris (1/8), Lepidium carlilacineum, Nasturtium montanum (1/2), Raphanus Sativus (2/3). 

Protoberberine Alkaloids.—In the course of the bioconversion of the proto-berberine scoulerine (65) into chelidonine (62) and phthalide-isoquinolines, e.g. narcotine (63), C-13 becomes oxidized.61 Ophiocarpine (68), with a hydroxy-group at C-13, represents an intermediate stage in the modification of the protoberberine skeleton, and results62 of tracer experiments have shown that scoulerine (65) is also to be included in the biosynthesis of this alkaloid. Tetrahydro-protoberberine (67) is also a precursor, its incorporation indicating that C-13 hydroxylation is a terminal step. As for other protoberberine derivatives,63 nandinine (64) was not assimilated,62 and it follows then that (65) is probably converted into (67) by way of isocorypalmine (66). 

In this chapter, we review the enantioselective proto nation of enols/enolates where the asymmetry is brought by cinchona alkaloids, either the natural products or some analogues. The cinchona alkaloids may act as a direct protonating agent of enolates or as an acid-base bifunctional catalyst by first deprotonating the substrate to generate the enolate and then, as an acid, by reprotonating the carbanion. 

The use of u.v. spectroscopy to determine the nature and position of methoxy-and methylenedioxy-substituted aromatic rings has been systematically applied to protoberberine, protopine, benzophenanthridine, and proto-ochotensimine alkaloids.51 I.r. spectra of examples of almost all subgroups of benzylisoquinoline alkaloids, including emetine, have been recorded and characteristic bands in the 1800—1480 cm-1 region have been used to identify a particular subgroup.52... 

The thermal decomposition of tetrahydroberberine methine base hydrochloride has been shown to yield an epimeric mixture of the rearranged product (216).215 An interesting transformation of a protoberberine into a benzophenanthridine alkaloid is discussed in Section 3J. Other work dealing with the synthesis of proto-berberine-type structures has been reported.216—218 A procedure for the preparation of radioiodinated (131I) berberine has appeared.219... 

Two intriguing models for the biogenesis of spirobenzylisoquinoline alkaloids have been proposed.246,247 Knowledge that aurotensine (265) and other proto-berberine-derived alkaloids co-occur with ochotensine, a spirobenzylisoquinoline... 

Various Reactions in the Side-Chains of Thiophens. - The preparation of various iV-substituted thieno[3,2-/]morphans from 2,5-dimethylthieno[3,2-/Jmorphan has been described. Several thiophen isosteres of proto-berberine alkaloids have been prepared, starting from amides between 3-thienylacetic acid and substituted )3-phenylethylamine or 3-(3-thienyl)ethyl-amine, followed by classical cyclization to dihydroisoquinolines, reduction to the tetrahydro system, and Mannich-type reaction with formaldehyde. 

Alkaloids represent one of the largest class of natural products with over 12000 defined structures [1], They can be summarized as nitrogen containing, mostly N-heterocyclic substances whose carbon skeleton is derived from amino acids. In a broader definition this group includes proto- and pseudoalkaloids and a number of microbial metabolites that are usually classified as antibiotics. In this review a broad definition of what to consider an alkaloid was chosen, albeit the emphasis is on alkaloids sensu strictu. 

A new tetrahydroprotoberbine alkaloid is tetrahydrothalifendine (132), found in Thalictrum fendleri Engelm. ex Gray (Ranunculaceae). The first known dimeric proto berberine alkaloid is bisjatrorrhizine (133), obtained from the root of Jatrorrhiza palmata (Lam.) Miers (Menispermaceae) and synthesized by oxidative dimerization of jatrorrhizine. ... 

ISOLATION. Rubijervine was first obtained by Wright and Luff from the rhizomes of V. album (69). Subsequently, Jacobs and Craig (32) gave a more exact description of its isolation. The benzene-extractable alkaloid mixture first deposited the sparingly soluble proto-veratrine and other crystalline bases. The amorphous residue was digested with methanolic sodium hydroxide at 60°. The hydrolyzate on fractional crystallization from chloroform-ethanol yielded rubijervine, isorubijervine, and germine in pure form. 

C. H. Heathcock, S. Piettre, R. B. Ruggeri, J. A. Ragan, J. C. Kath, Daphniphyllum alkaloids. 12. A proposed biosynthesis of the pentacylic skeleton, proto-Daphniphylline, The Journal of Organic Chemistry 57 (1992) 2554-2566. 

FIG. 2 Biosynthetic pathway leading from (S)-reticuline to the proto-berberine alkaloids in Berberis and Coptis. 

Humankind also produces alkaloids. For example, we are continuously producing alkaloids such as l-DOPA (3,4-dihydroxyphenylalanine), adrenaline (epinephrine), serotonin, etc. in our bodies (Chapter 1.2).These alkaloids are formed from amino acids through various oxidation and decarboxylation steps. Occasionally, they are referred to as proto alkaloids or biogenic amines. 

Alkaloids of the benzylisoquinoline type occur mostly in the genera Fagaropsis, Phellodendron, Tetradium, Toddalia (Toddalioideae), and Zanthoxylum Fagara) (Rutoideae) a group of genera considered to represent the proto-Ruta-ceae (Ng et al., 1987 Waterman and Khalid, 1981). 

This group of about 40 alkaloids is known only from the Papaveraceae (Guinaudeau and Bruneton, 1993 Ronsch, 1986). These compounds probably are derived from proto-berberine precursors (Santavy, 1979). (13R)- and (135)-scoulerine (72) are converted in plants of Papaver rhoeas into rhoeadine (89) (Fig. 32.29). This alkaloid had lost 79% of the tritium label from the (135) precursor, whereas the alkaloid retained 74% of the label from the (13/ ) precursor. Although the starting materials were not completely confor-... 

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