Necic acids structure

The known alkaloids senecionine, senkirkine, and retrorsine have been isolated from Senecio vernalis Wald, et Kit. by Roder et al.26 A new alkaloid, named senecivernine (59), was also present. The mass spectrum of (59) showed a molecular ion at m/z 335, and fragment ions at m/z 291, 248, and 220, characteristic for a macrocyclic diester of retronecine, arising from cleavage of the allylic ester.17 Basic hydrolysis of senecivernine gave a new necic acid which had spectroscopic data in accord with the proposed structure. Retronecine was not isolated. The necic acid from senecivernine is a Ci0 acid of an unusual structural type (cf. Vol. 8, p. 55). 

Axillarine (40) was isolated from C. axillaris Ait. by Crout.20 The crystal structure of the ethanol solvate of axillarine hydrobromide has been determined by X-ray diffraction methods.21 The absolute configurations of the four chiral centres in the necic acid portion have been established. The overall shape of axillarine is somewhat similar to fulvine (41),22 which also has an 11-membered macrocyclic... 

The absolute configuration of monocrotalic acid (44), the necic acid component of monocrotaline (45), has been elucidated aside from the acid derived from retusamine, whose structure has been defined by X-ray crystallography, this is the first necic acid component of a pyrrolizidine diester alkaloid containing an eleven-membered ring to have its stereochemistry unambiguously established. 

Axillarine and axillaridine therefore contain Cjo necic acid components belonging to a new structural type. The four groups of necic aads previously known, of which senecic acid (63) may be cited, contain a common C5 structural component [indicated to the right of the dotted line in (63)], which suggests that in the biosynthesis of the necic acids this unit is coupled to various intermediates derived from common amino-acids. In the biosynthesis of axillarine and axillaridine, however, it would appear that this same C5 unit is involved, but with a different mode of coupling to the other 5-carbon unit. This adds credence to the earlier proposal that in the biosynthesis of the necic acids, the common C5 unit (derived from isoleucine ) is coupled as an intact unit. ... 

The writer prefers structure CLXIc for this necic acid by analogy with other acids derived from alkaloids of Senecio species, on the usual requirement of an a-hydroxyl for lead dioxide oxidation, and on the basis of possible biosynthesis (74). 

Structure CLXXXVIII for monocrotaline also satisfactorily accounts for its transformations by the action of alkali into retronecine, o,/S-di-methyllevulinic acid, ethyl methyl ketone, and carbon dioxide (142). Saponification of the alkaloid may follow or precede the breakdown of the necic acid portion of the molecule (74). 

With the foregoing information, partial structures of the necic acid corresponding to sceleranecic dilactone and of the C8H12O4 oxidation product may be written as CXCVIII and CXCIX, respectively. Structure CXCVIII satisfies the 8- and y -lactone formation, especially the... 

With a knowledge of the structures of the necines and necic acids and with the location of ester linkages ascertained, it is possible to write structural formulas to represent the pyrrolizidine alkaloids. Configurations (absolute and relative) at asymmetric carbons and double bonds are indicated when the author feels that these have been established with a reasonable degree of certainty. Structures have not been provided where the information is deemed insufficient, so that not all of the alkaloids listed in Table 1 will be given representations. The alkaloids are divided into three main categories monoesters, diesters (two different necic acids), and cyclic diesters. The amine iV -oxides are not given since their structures are obvious from the amines. 

The necic acids, which have not been previously reported, and those for which further information has become available since (1) (see Table III in Volume VI, Chapter 3) are shown in Table V with their structure and the new parent alkaloids. 

Clivonecicacid, C10H12O4 [mp 142°-144° [a] — 208° (ethanol), -91° (water)], obtained by Klasek (10) from clivorine by alkaline hydrolysis has been assigned the absolute structure by Cervinka 141) with an S-configuration at C-2 and hence may be regarded as dehydrohygrophylli-necic acid. 

The general structure CXLIII of the Cio necic acids envisaged as two units advanced originally by Kropman and Warren 174) has been found in 12 acids shown in Chart IV. The structures of sceleranecic acid (CXLa)... 

Chart IV. The necic acids having the structure of Cio adipic acids. 

The previously proposed structure (5) for swazine has been revised to (6) with reversal of the mode of attachment of the necic acid to the necine base, retronecine. The revised structure brings swazine (6) into line with the majority of cyclic diester ... 

Of all the Senecio alkaloids, the structure of monocrotaline is known with most certainty as a result of the work of Adams and his co-workers over a period of five years or more. The alkaloid monocrotaline (I) is the ester of retronecine vith monocrotalic acid. The structure of the necine portion has been proved conclusively, while the structure of the necic acid portion is considered the most likely of three possible configurations. The position of attachment of the two portions is known with certainty. The... 

These illustrations may be regarded as typical experimental procedures for the extraction, hydrolysis, and hydrogenolysis of a Senecio alkaloid. In order to assign a structure to a particular Senecio alkaloid, it is first necessary to prove the structure of the portions obtained on hydrolysis and hydrogenolysis of the alkaloid. Accordingly, the structure of the necines and necic acids will be considered before that of the parent alkaloid, which is necessarily represented by their combination. 

The necic acids are those acids which are bound in ester combination with the hydroxyl group of the necines. Due to the wide divergencies in composition, properties, and structure, they will be treated individually in the order of increasing carbon content. 

Pyrrolizidine alkaloids (PAs) belong to a class of naturally occurring compounds characterized by a bridged dipyrrole structure. They encompass more than 400 different structures, which consist of a necine base of type 25 that may also be saturated between carbons 1 and 2 and esterified with one or more necic acids which exist as 5-11 carbon membered types (Figure 5.25). Thus, there are monosters such as supi-nine 27, indicine 28 obtained from retronecine 25a, and (-)-trachelanthic acid 26. Heliosupine 29 is an example of an open-chain diester, and retrorsine 30 is, instead, a macrocyclic diester. PAs are constitutively produced by the plant and are believed... 

Figure 5.25 Pyrrolizidine alkaloids structure of necine base 25, trachelanthic acid 26, a necic acid supinine 27 and indicine 28, monoester pyrrolizidine alkaloids heliosupme 29, a diester pyrrolizidine alkaloid retrorsine 30, a macrocyclic diester pyrrolizidine alkaloid senecionine N-oxide 31, a non-toxic pyrrolizidine alkaloid.

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