Securinine alkaloids

Although reference to individual securinine alkaloids have been made in previous volumes of this treatise (Vol. VII, XIII) and the literature dealing with work since 1969 has been summarized (9), no comprehensive review on this subject has appeared. It is the purpose of this contribution to fill this gap in the alkaloid literature. Coverage is complete through March 6, 1972 Chemical Abstracts. 

Undoubtedly owing to the potentially beneficial biological activity of the securinine alkaloids (Section V) most of the synthetic work has been covered by patents (71, 72). 

The potential pharmacological properties of securinine alkaloids (Section V) no doubt are responsible for the development of teehniques suitable for both rapid and exact analysis of these alkaloids (Table V) (84-94). A number of other papers have dealt with determination of the most effective methods for alkaloid extraction (86, 95, 96). 

Securinine [3610-40-2] (137), C 2H 5N02, is the major alkaloid of Securinega surroticosa Rehd. and has been shown to arise from two amino acid fragments, lysiae (24) andtyrosiae (25). 

Reactions at the aromatic nucleus that are quite different from the usual mild condensations and rearrangements which apparendy generate the typical alkaloids already discussed must be iavolved. Securinine (137) is reported to stimulate respiration and increase cardiac output, as do many other alkaloids, but it also appears generally to be less toxic (98). 

Carbon-13 n.m.r. assignments have been reported for a number of isomeric 3-butyl-5-methyloctahydroindolizines that were synthesized in studies of the trial pheromone of the Pharaoh ant, and for some closely related indolizidines. This work includes a detailed discussion of the preferred conformations of these compounds.15 Securinegine, a minor alkaloid from Securinega suffruticosa Rehd., is isomeric with securinine, and the structure (22) has been proposed.16... 

Securinine.—Further details of one group s study of the biosynthesis of securinine (13) have been published.21 The origins of this alkaloid are well defined,22 and information which adds to this definition is that tyrosine is incorporated without loss of tritium from the carbon atoms flanking the phenolic hydroxy-group.21... 

Rather similar degradation processes are reported for the indolizi-dine alkaloid securinine.66... 

BicucuUme (AA), cryptopine, hydrastine, corlumine, and related isoquinoline alkaloids (AA) securinine harmaline and related (J-carbohne alkaloids (A) muscimol (A) securinine (AA)... 

DL-[2- C]Lysine [as (1)] and [2- C]-A -piperideine [as (2)] afforded securinine (3) in which the label was confined essentially to the asterisked carbon atom. Further, [i 5-6- H 6- C]-DL-lysine [as (1)] gave securinine without loss of tritium. Consequently C-6 of lysine does not undergo oxidation in the course of securinine biosynthesis and so the e-amino-group of (1) must be retained whilst the a-amino-group and carboxy-function are lost. The combined results are consistent with the hypothetical route to securinine shown in Scheme 1. This pathway will now gain more validity if alkaloids with structures similar to those of the proposed intermediates can be found in Securinega or related plants. 

It is interesting to note that securinine (3) is the first among those alkaloids with a nitrogen atom common to two rings which is known to avoid a symmetrical intermediate (c/. ref. 17). 

Seourinine, the most abundant alkaloid of this group, was first isolated by Russian workers in 1956 but its structure was fully established only in 1962. In the subsequent years a variety of alkaloids of the same skeletal type (1) but differing in stereochemistry and minor functionality were isolated and characterized. More recently, three alkaloids possessing a lower homolog structmre (2) of the seourinine type were discovered. Table I lists the known alkaloids according to these two subgroups. Several alkaloids (phyllanthidine, suffruticodine, and suffruticonine) have not been structurally elucidated but their molecular formulas and spectral properties indicate most probably a securinine-type skeleton (Section II, L). 

Securinine, the major alkaloid in the leaves of Securinega suffruticosa (Pall.) Rehd. was first described by Murav eva and Bankovskii (10, 11). These Russian workers determined the empirical formula (CisH gNOg) and some other physical properties of securinine and prepared a series of derivatives. They also established the absence of A-methyl, 0-methyl, hydroxyl, methylenedioxy, and ketone groups by functional group analysis and the presence of a lactone moiety and extended conjugation by IR and UV spectroscopy (12). The skeletal structure was first established independently and almost simultaneously by two Japanese teams on securinine isolated from domestic S. suffruticosa plants (13, 14). Subsequently, securinine was also isolated from... 

Aside from securinine, allosecurinine is the only other Securinega alkaloid whose structure and relative stereochemistry has been confirmed by X-ray analysis. Although Nakano s stereochemical investigations (Section II, G) pointed to a trans A/B ring junction (103) for allosecurinine, the X-ray determination on allosecurinine methiodide showed a cis A/B arrangement (104) (41). This is almost certainly a... 

Thus allosecurinine (96) is a C-2 epimer of securinine (27). Further stereochemical interrelationships of allosecurinine with other Securinega alkaloids which establish its absolute configuration as represented by formulation 96 are described in Section II, G. 

In their structural elucidation work on securinine and allosecurinine, Parello et al. carried out detailed NMR analysis by which they were able to assign precisely most of the protons in the alkaloids 16). Subsequently, Parello elaborated on certain aspects of these assignments 41a) and also investigated the NMR spectra of dihydro and tetrahydro derivatives of these alkaloids with the aid of deuterated... 

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