Strychnine structural formula

Alkaloids are compounds of biosynthetic origin that contain nitrogen, usually in a heterocyclic ring. These compounds are produced by plants in which they are usually present as salts of organic acids. They tend to be basic and to have a variety of physiological effects. One of the more notorious alkaloids is cocaine, and alkaloidal strychnine is a deadly poison. The structural formulas of these compounds and three other alkaloids are given in Figure 15.10. 

Although the correct structural formula had been intuitively proposed earlier, the structure of strychnine was founded on a firm basis only when Woodward 6t al.8 discovered that strychnone obtained from the oxidation of IP-strychnine gave ultra-violet absorption maxima resembling those of N-acylindoles. Strychnine, oh the other hand, gives bands similar to N-acyldihydroindoles. Woodward and McLamore recently established the structure of another alkaloid, semperivinine, on the basis of its ultra-violet absorption spectrum. (For absorption data of alkaloids. see references 94 and 95.)... 

Comparatively few alterations have been made since 1989 in the structures accepted for well-known alkaloids. A slight but important change has been adopted in the formula of strychnine and contributions to the chemistry of that alkaloid and its associates are still being made, though the formula seems now so well established that Woodward has recently suggested and discussed a scheme for the biogenesis of strychnine on which Robinson has commented favourably. Robinson has also proposed a scheme for the biogenesis of emetine. This involves a modification in the formula of that alkaloid, which is supported by Dewar s interpretation of the results of recent chemical work on emetine by Karrer et al., by Spath and by Pailer. ... 

The conquest of strychnine has finally been achieved, after almost a century and a half of prodigious effort. The ultimate conclusion from the herculean assaults of the degradative chemistsf has now been confirmed in full structural and stereochemical detail with the announcement of the complete delineation by X-ray crystallography (299, 300) and the total synthesis of the molecule (301, 302), which may be represented by the formula overleaf ... 

In conclusion, the completed X-ray crystallographic studies on the structure of strychnine salts from two laboratories have been published (299, 300) and find themselves in complete agreement with the formula derived by chemical means and now synthesized. The conformational conclusions from these sources are best summarized, and the singular intricacy of the strychnine architecture pictorialized, in the following expression ... 

In the event of the validity of Leuchs objection to Robinson s strychnine formula, alternate positions for the location of the ethanamine side chain must be considered, namely, Cs or Ce. The modified structure L has also been considered. The location of the carbonyl group in curbine at Ce eliminates this position from consideration. Furthermore, the formation of carbazole from strychnine would be hard to accommodate on L without the assumption of an attendant rearrangement, while the C5 and... 

If the nuclear structure of vomicine may be represented in a manner similar to that shown in strychnine formula LXXXIX then it is understandable why CXXII and CXXIV should differ from vomipyrine. 

Today the molecular formula and the obvious chromophoric moieties along with the type of double bond can be established rapidly by techniques which allow by and large for complete recovery of the alkaloid in question, e.g. for strychnine (Chart 3.1) the units shown by the more heavily shaded positions. This sort of information was available in the past via pyrolytic methods and two examples are given for strychnine and yohimbine in Chart 3.1. It can be seen that despite the so-called brutality of the method it did provide accurate structural information the problem being, of course, that in hindsight it is more obvious. 

The carbon patterns of the products (Chart 3.1) of the drastic degradation of strychnine can all be discerned in the parent molecule but cannot by themselves be used to deduce a unique formula. That the A and B rings were six and five membered respectively was reconfirmed over the years often at the cost of considerable labour. One such case concerned dinitrostrychol-carboxylic acid, one of the nitric acid oxidation products of strychnine. It was first obtained about the turn of the century and after considerable work in the late twenties was found in the early thirties to be 5,7-dinitroindole-2-carboxylic acid. Actually the structure of strychnine would probably have been realized much earlier than it was if any one of a number of degradations had been persevered with in a systematic way. The constitution arrived at by the chemical methods rests on the properties of the functionalities in their special environments and their interlocking reactions. The advent of commercial recording infrared and ultraviolet machines played an important part in the latter phase of this work. A synthesis of the alcohol, isostrychnine I (strychnine with its cyclic ether opened at dotted line and A double bond) has confirmed these conclusions as has the determination of the structure and absolute stereochemistry by the X-ray crystallographic method. 

AspMospemiine. The first inkling that the structure of aspido spermine was different firom the yohimbine or strychnine types was the formation on zinc dust distillation of 3,5-diethyIpyridine and since this carbon nitrogen pattern turned out not to be present in the original alkaloid it could only lead to erroneous formulae, which it did. The nature of rings A and B became clear... 

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