Strychnine chemical structure

L. B. Slater, Woodward, Robinson and strychnine chemical structure and chemists challenge , Ambix, 2001, 48, 161-189. 

The dopaminergic potential of the Dendrobium species is, to date, open for exploration. An interesting feature of the Dendrobium species is their ability to elaborate sesquiterpene alkaloids, the chemical structure of which resembles the one of strychnine. One such alkaloid is dendrobine, which is widespread in the genus. Kudo et al. noted that dendrobine, isolated from Dendrobium nobile, exhibits a strychnine-like presynaptic inhibition in frog spinal cord (64). 

Using either of the methods just described in successive steps allows the identification of progressively larger fragments of the chemical structure of the molecule being studied or elucidated. In the case of strychnine, 1, shown... 

Sweetness Production by the Combination of Bitter and Sweet Tastes. Sensory tests using typically bitter compounds such as brucine, strychnine, phenylfiiiourea, caffeine and bitter peptides were performed. Sensory tests using typically bitter compounds such as brucine, strychnine, phenylthiourea, caffeine and bitter peptides were performed. Sensory taste impression were also measured for combinations of acetic acid (sour) and typical bitter compounds (5). The data from these studies indicated that the tastes of ese bitter/sour mixtures changed to a sweet taste regardless of their chemical structure of the bitter component (Table II). 

The data shown in Table 2 illustrate the general paucity of comparative toxicity data within an isosteric series of chemicals. In this Table a variety of toxic end-points observed for benzene and naphthalene have been compared with those of their simple heterocyclic analogues, and it is clear that it is almost impossible to derive chemical structure-biological activity relationships from the published literature for even such a simple series of compounds. Even basic estimates of mammalian toxicity such as LD50 values cannot be accurately compared due either to the absence of relevant data or the noncomparability of those available. Thus in a field where there are little comparative data on the relative toxicity to mammals of pyrrole, thiophene and furan for example, it is difficult to relate chemical structure to biological activity in historical heterocyclic poisons such as strychnine (3) and hemlock [active agent coniine (4)]. 

The toxiferines (see Figure 6.85, page 359) also share the diquaternary character. Alcuronium is a semi-synthetic skeletal muscle relaxant containing the dimeric strychnine-like structure and is produced chemically from C-toxiferine (see page 360). 

Fig. 3 Structural diversity of bitter compounds. The chemical structures of absinthin, aristolochic acid, denatonium, strychnine, D-(-)-salicin, and phenylthiocarbamate (PTC) are depicted. Note the different sizes, charges, and three-dimensional architectures of these compounds that all activate at least one of the human bitter taste receptors...

Ptomaines. Name, derived from modern Greek ptoma=cadaver, for the so-called cadaveric poisons formed from putrefying proteins. The enzymatic decarboxylation products of the amino acids lysine and L-omithine ( cadaverine and putrescine), previously known as R, are, however, relatively non-toxic biogenic amines. Today the name P. is used for the toxic metabolic products of putrefactive bacteria that colonize rotting, protein-containing foodstuffs such as meat, fish, etc. These P. have widely differing chemical structures their activities are purported to be similar to those of the plant toxins such as strychnine, atropine, etc.. 

Strychnine and brucine were isolated as the main alkaloids of vomica (also known as nux vomica in other parts of the world). Strychnine was isolated at the beginning of the nineteenth century, but it was not until the middle of the twentieth century when the chemical structure of this alkaloid was clarified [1]. The now-classic total synthesis of strychnine was achieved by Woodward et al. [2]. 

The Strychnos alkaloids possess diverse chemical structures that have attracted considerable attention in organic synthesis during the last decades. Recent studies on the synthesis of akuammicine, strychnine and leuconicine A and by Andrade et al. proved that the intramolecular Heck reaction is extremely valuable for the construction of complex polycyclic molecules. Based on Rawal s method for the construction of the D ring of Strychnos alkaloids, vinyl iodides 37, 39, and 42 undergo a regioselective and stereoselective palladium-catalyzed cychzation in the presence of Pd(OAc)2, PPha in Et3N to furnish ( )-akuammi-cine 38, and the advanced intermediates 40 and 43 in excellent chemical yields (Scheme 13.11). 

In the post-World War II years, synthesis attained a different level of sophistication partly as a result of the confluence of five stimuli (1) the formulation of detailed electronic mechanisms for the fundamental organic reactions, (2) the introduction of conformational analysis of organic structures and transition states based on stereochemical principles, (3) the development of spectroscopic and other physical methods for structural analysis, (4) the use of chromatographic methods of analysis and separation, and (5) the discovery and application of new selective chemical reagents. As a result, the period 1945 to 1960 encompassed the synthesis of such complex molecules as vitamin A (O. Isler, 1949), cortisone (R. Woodward, R. Robinson, 1951), strychnine (R. Woodward, 1954), cedrol (G. Stork, 1955), morphine (M. Gates, 1956), reserpine (R. Woodward, 1956), penicillin V (J. Sheehan, 1957), colchicine (A. Eschenmoser, 1959), and chlorophyll (R. Woodward, 1960) (page 5). ... 

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. ... 

Although far less numerous than the terpenoid/isoprenoid or polyketide NPs, the alkaloids (with an estimated 20,000 different structures) have a special place in NP research because a few are of great value to humans—for example, morphine, theobromine, caffeine, vincristine, quinine, codeine, cocaine, nicotine and strychnine. These often complex chemicals are found in about 20% of vascular plants and a smaller number of fungi, marine invertebrates and a few bacteria. ... 

Strychnine is a famous poison featured in many detective stories and a molecule with a beautiful structure. All chemists refer to it as strychnine as the systematic name is virtually unpronounceable. Two groups of experts at IUPAC and Chemical Abstracts also have different ideas on the systematic name for strychnine. Others like this are penicillin, DNA, and folic acid. 

The very interesting stereochemical arguments based on the chemical properties of strychnine and its degradation products, that were elaborated by Holmes and published in 1952 (38), did not prove the complete stereochemistry of the molecule, but they did show that all the previous observations that had stereochemical implications were in accord with the X-ray structure. 

The labors of Pasteur and others have completely established the correlation which exists between molecular asymmetry and rotatory power. If the asymmetry exists only in the crystalline molecule, the crystal alone will be active if, on the contrary, it belongs to the chemical molecule the solution will show rotatory power, and often the crystal also if the structure of the crystal allows us to perceive it, as in the case of the sulphate of strychnine and the alum of amylamine. 

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