Evoninic acid

Natural sesquiterpene pyridine alkaloid formation needs two precursors, one for the pyridinium moiety and another for the sesquiterpene moiety. The a for formation of the pyridinium moiety is nicotinic acid, which reacts with isoleucine and, by oxidative reaction, produces evoninic acid, wilfordic acid or edulinic acids, a for the sesquiterpene moiety is still open to question, but E, E-famesyl cation has been suggested as one possibility and hedycarylol as a second. This moiety is dihydroagarofuran. Therefore, a for the sesquiterpene pyridine alkaloids is nicotinic acid and E, E-famesyl cation and, controversially, hedycaryol. The /3 is amacrocycling ring formation substance (two moieties), from which the alkaloid forms (Figure 62). 

In early work Stockman (8,9) had obtained an alkaloid preparation from khat which he called cathidine, and mass spectrometric examination of an old preparation led Luftmann and Spiteller (44) to the view that it was a mixture based on a reduction product of the evonine sesquiterpene core esterified with acetic, benzoic, trimethoxybenzoic, nicotinic, and evoninic acids. Ginsburg and colleagues (45) also examined cathidine which they had reisolated from khat and found that it contained at least four compounds. One of these, cathidine D, was studied in some detail and formulated as being either 28 or 29 (45). 

The acids which esterify the core were isolated as esters from the alcoholysis. Both cathic (38) and edulinic (37) acids were new acids, and their structures were determined from chemical and spectroscopic studies evoninic acid was already known from previous work on celastraceous alkaloids. Simpler acids were identified and quantified by NMR and GLC means. 2-Hydroxyisobutyric acid had not been found previously as an esterifying acid in celastraceous alkaloids, and its high water solubility and steam volatility made it difficult to isolate an added difficulty was its tendency to react by a B l2 mechanism in alcoholysis, giving the free acid when the ester was expected. 

The edulinic acid residue found in K17 and K19 may share a similar bio-genetic origin to evoninic acid. Both may be viewed as products of coupling of (at a different oxidation level) nicotinic acid (or quinolinic acid) at C-2 with C-4 or C-5 of isoleucine as in 63. The absolute configuration at C-3 of isoleucine is the same as at C-8 of evoninic acid, but that of edulinic acid is not yet known. 

A synthesis of the racemic diastereoisomers of evoninic acid has been reported by Pailer and Pfleger 64). 2-Ethyl nicotinate was brominated to form 78, and the... 

Acanthothamine (45) was isolated from Acanthothamnus aphyllus, and its structure was determined using H NMR, 13c NMR, and chemical transformations [164]. The position of the secondary hydroxyl groups was established after oxidation of 45 with pyridinium dichromate followed by H NMR analysis. Methanolysis of 45 followed by 1h NMR analysis demonstrated that an iso-evoninic acid residue was present [ 164], X-ray crystallography confirmed the proposed structure and established the absolute stereochemistry for the cvoninic acid residue as 1R, 185 [165]. 

Two new evoninate-type alkaloids have recently been described, peritassin A and B, obtained from species of the genus Peritassa. These structures are distinguished by the macrocyclic unit which consists of an evoninic acid isomer in which the pyridine ring of the dibasic acid is substituted at 4 -5 instead of the more usual substitution of evoninic acid at 2 -3 [44],... 

Concurrent investigations in several parts of the world helped to establish the structures of a series of alkaloids from Euonymus europaeus and E. siebol-dianus. Japanese workers deduced the structure of evonine (61 R = R = Ac, R = OH, R = O) by extensive spectral analysis and chemical degradation.Earlier work had established the structure and stereochemistry of evoninic acid (68 R = H), obtained by basic hydrolysis of evonine. More... 

Once the structure ofevonine was established as (61 R = R = Ac,R = OH, R = O), related alkaloids isolated from Euonymus sieboldianus (see Table) were readily shown to be slight functional group modifications of this major alkaloid by spectral comparison and simple chemical transformation. Further confirmation of the manner in which evoninic acid (68 R = H) is attached to the sesquiterpenoid portion was also obtained in this study. The stereochemistry of evonine indicated in structure (61) and thus also of neoevonine, euonymine, and neoeuonymine (see Table) were advanced on the basis of n.m.r. and nuclear Overhauser effect experiments. ... 

H)2,3f dimethyl -3-(3 carboxy-2-pyridyl )-propionic (evoninic) acid... 

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