Biogenetic analyses

Another approach ( biogenetic analyses ) involves considerations of a reasonable biogenesis of a target compound. Reflections on relationships of components which belong to the same odour bouquet or which have already been known from related species may suggest structures to be expected and, thus, be helpful in the identification process. 

Since then, more polycyclic alkaloids whose rings lack methyl groups have been described. Retro-biogenetic analyses of the new related metabolites have been proposed in recent publications. These studies have outlined how the seemingly varied frameworks of such compounds are actually analogous. 

Fig (5). Biogenetic analysis of marine sponge alkaloids formed by the condensation of ammonia, acrolein and an acyclic dialdehyde. 

This type of biogenetic analysis, based essentially on the acetate hypothesis, combined with an analysis of structural relationships... 

COSY, HMQC, HMBC, and HSQC-TOCSY NMR spectra. The relative stereochemistry of each of the piperidine rings in 21 was estabhshed by analysis of NMR and NOESY spectra. However, the authors have not obtained experimental data to relate the relative stereochemistry of each piperidine moiety to the other. They suggested the relative stereochemistry indicated in 21, based on the Baldwin and Whitehead biogenetic proposal [24] (see below) and also by comparison with data for haliclonacyclamine E (5) and arenosclerin A (14). 

On acetylation, a monoacetate (M+- 704) was formed in which a 1H singlet appeared at 5.20 ppm (versus 3.87 ppm in 242), suggesting the presence of a secondary hydroxyl surrounded by two nonprotonated carbons. This feature, coupled with biogenetic reasoning (see below) led to structure 242 for er-vafolidine, and it was further supported by comparison of the 400-MHz H-NMR spectrum with that of 3-epiervafolidine (243) (see below) whose structure was based on X-ray analysis. 

In the first place, the structure of the target molecule is submitted to a rational analysis in order to perceive the most significant structural features, and it may be useful to use different types of molecular models at this point. It should be remembered that a molecular structure has "thousand faces" and finding the most convenient perspective may greatly simplifly the synthetic problem. The synthesis of opium alkaloids, for instance, is much simplified if one realises that they are, in fact, derivatives of benzyltetrahydroisoquinoline (18) (see Scheme 3.8). This was indeed the inspired intuition of Sir Robert Robinson which led to the structural elucidation of morphine (19) and to a first sketch of the biogenetic pathway [22], and later on to the biomimetic synthesis of thebaine 20 [23] [24]. 

The revised structure for clavicipitic acid, suggested earlier by King etal.,44a has been confirmed, and the stereochemistry elucidated, by X-ray crystal-structure analysis.446 The major component of the naturally occurring mixture that constitutes clavicipitic acid was obtained pure by t.l.c. on silica gel, and proves to have the (55,10/ ) stereochemistry depicted in (53). The minor component of the mixture is presumably the (55,105)-diastereoisomer. It should be noted that, at present, the absolute configuration of clavicipitic acid rests only on its biogenetic derivation from L-tryptophan.446... 

Manzamines comprise a new group of /3-carboline alkaloids having polycyclic ring systems, the provenance of which is problematical as there appears to be no obvious biogenetic path. Manzamine A (180) was isolated from an Okinawan sponge (Haliclona sp.) and shown to exhibit antitumor activity. Its structure and absolute configuration were determined by X-ray analysis (150). From an Okinawan sponge (Pellina sp.) keramamines A (180) and B (181) were isolated as antimicrobial substances (151), and keramamine A was found to be identical with manzamine A. 

Daphnimacropine (17) has been isolated from the bark of D. macropodum and characterized as the corresponding methiodide, the structure of which has been reported by Nakano, Osaki, and their coworkers on the basis of an X-ray crystallographic analysis of the methiodide (15). Although the structure 17a thus obtained is of interest from a biogenetic point of view it is questionable on the basis of the following reasons ... 

Neodihydrothebaine (7), which was known as a synthetic derivative of the-baine (45), has been found in Papaver bracteatum, from which it was extracted as an inseparable mixture with bractazonine (8). The composition of the mixture was determined by GC-MS analysis and 1H-NMR studies and was further confirmed by comparison with an artificial mixture of synthetic neodihydrothebaine (7) and bractazonine (8) (24). Both alkaloids are considered to be biogenetically derived from thebaine (45) or its immediate precursor salutaridinol (103). 

Fiebig et al. (1985). It exhibited cytotoxic activity against certain cell cultures. Its structure was established as 1-m ethoxy -3-hydroxymethylcarbazole by analysis of spectroscopic data and was confirmed by partial synthesis from murrayanine isolated from M. siamensis roots. Koenoline exhibited cytotoxic activity against the KB cell-culture test system. Bhattacharyya and Chakraborty (1984) described mukonal, a probable biogenetic intermediate of pyrano-... 

X-ray analysis of the free base.4 The future study of the exact biogenetic pathway for the formation of this alkaloid should prove to be a fascinating endeavour. 

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