Structure elucidation, natural products

The tropane alkaloids are a well-recognized group of structurally related natural products. Long before elucidation of the structures, the mydriatic and anesthetic action of several compounds was exploited (6). The very extensive literature covering the pharmacological properties of the tropane alkaloids will be considered only briefly in this chapter. Readers with a deeper interest in the subject are referred to other publications (7-14) and to the references given in Section VII. 

In summary, NMR spectroscopy is an extremely versatile tool useful that enables researchers to understand the structure of natural products such as carotenoids. For a full structural assignment, the compound of interest has to be separated from coeluents. Thus, it is a prerequisite to employ tailored stationary phases with high shape selectivity for the separation in the closed-loop on-line LC-NMR system. For the NMR detection, microcoils prove to be advantageous for small quantities of sample. Overall, the closed-loop system of HPLC and NMR detection is very advantageous for the structural elucidation of air- and UV-sensitive carotenoids. 

The chemical structure of natural products can be identified quickly with a limited amount of materials by utilizing NMR equipment containing cryo probes [60]. More predictable chemical shifts coupled with a reasonable amount of published and internal NMR data [61] will significantly improve the time and accuracy of the structure elucidation process [62,63,64],... 

Historical The fruits of Strychnos nux-vomica (nux vomica, poison nut) were first described by Valerius Cordus in 1540 the alkaloid was isolated in 1818 by Caventou and Pelletier. The structure of S. was elucidated by Leuchs, Robinson, Woodward, and Prelog Woodward achieved the synthesis (30 reaction steps) in 1954 as the first total synthesis of a structurally complicated natural product. For further syntheses, see Ut . 

The absorption spectrum of a compound can be associated with a partial structure of the molecule (sometimes the whole molecule), and it can be expected that all molecules embodying that part as their only chromophore will have the same spectrum. This principle has been applied in the elucidation of structures of natural products Thus for example, it was found that the indole alkaloids have two absorption bands, at about 225 mp, 25000, and at 270-290 max 6000, as in ibogamine (85) alloyohimbine (86) and ajmalicine (87) , shown in Table 16. The enhanced absorption of 87 at 226 mp is due to superimposition of the absorption of the acrylic system also present in the molecule. Some care has to be taken when deciding which is the chromophore responsible for the absorption spectrum of a compound. Thus 2,3-dimethylindole (cf. 84) is a better choice than indole (84) itself, as a model for the spectra of alkaloids 85, 86, and 87, as shown in Table 16. 

NaturalProductReports is the new bimonthly journal that will continue the coverage of literature in these Specialist Periodical Reports and in the companion series The Alkaloids, Aliphatic and Related Natural Product Chemistry, and Terpenoids and Steroids supplemented by occasional reviews of areas of research in which progress suddenly increases and of those physical techniques which gain importance in the elucidation of the structure of natural products. 

However, better use of spectral information for more rapid elucidation of the structure of a reaction product, or of a natural product that has just been isolated, requires the use of computer-assisted structure elucidation (CASE) systems. The CASE systems that exist now are far away from being routinely used by the bench chemist. More work has to go into their development. 

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

H. Budzikiewicz, C. Djerassi and D. H. Williams, Structure Elucidation of Natural Products by Mass Spectrometry, Holden-Day, San Francisco, 1964, Volume 1, Chapter 2. 

Alkaloids containing a quinazoline nucleus form a small but important group of natural products and have been isolated from a number of different families in the plant kingdom. The quinazoline alkaloids are of the four types (48), (49), (50), and (51). The structures of arborine, peganine, febrifugine, rutaecarpine, and evodi-amine have been elucidated by degradation and synthesis and are described in recent reviews on quinazoline alkaloids. ... 

Ibid., Structure Elucidation of Natural Products by Mass Spectrometry,... 

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