Alkaloids, biogenesis, from amino acids

In the development of the theory that alkaloids derive from amino acids it was early suggested that the benzylisoquinoline bases could be formed by condensation of 2 molecules of tyrosine (CLI) via 3,4-di-hydroxyphenylalanine (CLII). Leete and Murril (229) have pointed out that if iV-norlaudanosoline (CLV R = H) is an intermediate in the biogenesis it could be formed by condensation of 1 mole of 3,4-dihydroxy-phenylethylamine (dopamine) (CLIII) and 1 mole of 3,4-dihydroxy-phenylpyruvic acid (CLI V) and the differential incorporation of each unit of tyrosine could be rationalized. When dopamine (CLIII) is the labeled material fed to the plant then the moiety of the suggested intermediate (CLV R = H) which derives from the pyruvic acid CLIV will not be radioactive. 

As far as the biosynthesis is concerned Winterstein and Trier pointed out in 1931 that, according to their structure, alkaloids must be derivatives of amino acids. Thus, an amino group supplies the N of the alkaloids. Today no one doubts the correctness of this statement. Indeed, their biogenesis from amino acids is that which allows the heterogeneous collection of alkaloids to be considered as a group. That does not exclude the possibility that sometimes building blocks other than amino acids, in particular isopentenyl pyrophosphate, can be drawn upon for the biosynthesis of alkaloids. 

This applies especially to substances such as the essential oils or lignin. The comparatively small amount of tvork so far done on the biogenesis of alkaloids from isotopically labeled amino acids suggests that theories of biogenesis of alkaloids from amino acids are probably justified. 

Similarities in structure commonly reflect similarities in biogenesis. Consideration of the architectural patterns and structural relationships of natural products enabled Collie, Robinson, Ruzicka and others to discern the biogenetic units from which certain phenolic compounds, alkaloids and terpenes were formed. A survey of the antibiotics indicates that one large collection of these substances can be derived mainly from amino acid residues, another mainly from acetate (or, on occasion, propionate) and a third from simple sugars. Some structures can be dissected into two or more different fragments that are derived from different types of biogenetic unit. 

The biogenesis of alkaloids from the aromatic amino acids forms an enormously rich field for work with modern isotopic and chromatographic techniques, which as yet has hardly been touched. 

The parent compound of the secoiridoids is secologa-nin (see secoiridoids), the most important intermediate in the biogenesis of alkaloids that are not derived from an amino acid. This includes most indole alkaloids, the ipecac, the Cinchona, and the pyrroloquinoline alkaloids as well as simple monoterpene alkaloids The best known biological property of the I. is their bitter taste. However, bitter principles are mostly not used as pure substances, instead alcoholic extracts are preferred to stimulate appetite (increased secretion of gastric juice). Furthermore, bitter substances are used to modify the taste of pharmaceutical products. Some I. exert various effects on the central nervous system as a consequence of their volatility and lipophilicity, e.g., nepetalactone, iridodial, teucrium lactones, and valepotriates. 

That tyrosine plays a role in the biogenesis of several types of benzylisoquinoline alkaloids results from its incorporation to the hydrophen-anthrene bases (thebaine, codeine, morphine) and to the benzylisoquino-lines papaverine, narcotine, and narcotoline w hen the generally labeled amino acid was fed to P. somniferum 219). 

Following up this idea they synthesized )8-carboline and 1-methyl-/3-carboline by reaction of tryptophan with formaldehyde and acetaldehyde, respectively, under oxidizing conditions. The steps of this biogeneticaUy patterned synthesis have been repeatedly studied and are fuUy discussed in Sections III, A, l,aand III,E,2,a,i. The formation of l,2,3,4-tetrahydro-)8-carbolines as the initial step in the biogenesis of jS-carboline alkaloids, by reaction of tryptophan or trypta-mine or the corresponding hydroxylated derivatives with aldehydes or a-keto acids, derivable from a-amino acids, is a widely held concept. Two lines of circumstantial evidence favor this hypothesis. First, a number of simple l,2,3,4-tetrahydro-)8-carboline derivatives have been found to occur naturaUy. l-Methyl-l,2,3,4-tetrahydro-]8-carbo-line (461 = B = H eleagnine) has been isolated from Elaeagnus... 

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