Biogenetic pathway

Chemical realization of the biogenetic pathways proposed for fused polycyclic ethers of marine origin 99H(50)561. 

Scheme2 Biogenetic pathway proposed by Crews et al. [25] and Garson et al. [19,20] for the formation of halicyclamine and haliclonaq clamine/arenosclerin alkaloid skeletons...

Scheme 4 Biogenetic pathway proposed by Cimino et al. [30] for the formation of misenine (41)...

Scheme 5 Biogenetic pathway proposed by Andersen et al. [33,34] for the formation of the madangamine skeleton...

Synthesis of ( )-untenone A from 5-substituted furylacetate 50 by using bromine oxidation in MeOH followed by acidic hydrolysis, an approach based on a likely biogenetic pathway, has appeared <00TL3467>. 

In the particular case of natural products, once all the possibilities that the "logic-centred methodology" offers have been explored, it is pertinent to consider the biogenetic pathways by which they are synthesised in Nature since these can be a source of inspiration and may introduce an intrinsic element of elegance into the synthetic plans. In this context, tropine (131 offers a unique example in the history of organic synthesis. In 1902 this rather simple alkaloid was synthesised by Willstatter from cycloheptanone [8] through a sequence of about twenty steps, as shown in Scheme 3.4. 

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]. 

Strategies based on biogenetic pathways which apply only to natural products as in, for instance, usnic acid, tropinone, thebaine, strychnine, steroids etc. 

It is difficult to reconcile the unique chemical structure of tetrodotoxin with that of an animal product. Its structure is not related to that of other animal products by any readily recognized biosynthetic scheme. It is not a terpenoid, not obviously formed from amino acid or carbohydrate units, and apparently not constructed from acetate or propionate units. Nor does it resemble any of the various plant alkaloid patterns. It thus appears to be a very unlikely animal product to result from known biogenetic pathways. In this connection the metabolic incorporation of radioactive precursors using torosa and ]C. granulosa salamanders was studied by Shimizu et al. (47). They observed significant isotopic incorporation into amino acids and steroid metabolites, but they found no such incorporation associated with tetrodotoxin. 

In the biogenetic pathway depicted in Scheme 3.1 (362-366), the formation of 3-methylcarbazole (2) it is considered to arise from 3-prenylquinolone (402) through 2-prenylindole (403). Although 2-prenylindole alkaloids are rare in nature, there is another major source in the Rutaceae in the form of the dimeric indoles of Flindersia fournieri, such as isoborreverine, which could arise from the monomeric units of... 

The biogenetic pathway proposed by Chakraborty for the formation of carbazole (1) and 3-methylcarbazole (2) proceeds through Af-phenylated anthranilic acid (406). This hypothesis is based on aromatic C-methylation of aniline with methionine, and originates from anthranilic acid (397) and prephenic acid (404). Until now, there are no N-phenylated anthranilic acid derivatives known naturally, therefore, this hypothesis is lacking substantial biogenetic evidence. However, the isolation of carbazole (1), 3-methylcarbazole (2), and several derivatives of 3-methylcarbazole... 

Owing to their pleasant odours many y-lactones and d-lactones are known to be Important flavour compounds of fruits and contribute essentially to the characteristic and distinctive notes of strawberries, peaches, apricots and many other fruits [24]. Chiral aroma compounds from fruits and other natural sources are characterised by origin-specific enantiomeric ratios, as their biogenetic pathways normally are catalysed by enzymes. 

From the analytical point of view, it is worth noting the biogenetic pathway of 2-methylbutanoic acid starting from isoleucine [(2S)-amino-(3S)-methylpenta-noic acid]. The (S)-configuration of the precursor is expected to remain but also enzymatic racemisation (by enolisation of the intermediate 2-oxo-3-meth-ylpentanoic acid) is known from the literature. It is not surprising that in some cases 2-methylbutanoic acid is detected as an enantiomeric ratio more or less different from the expected homochiral S enantiomer (Table 17.2) [35-40]. 

The structural similarity between arsenobetaine and glycine betaine suggested that arsenic may substitute for nitrogen in pathways of phospholipid biosynthesis and was the basis for a proposed biogenetic pathway for arsenobetaine (174). The proposed pathway begins with arsenic present as either arsenoethanolamine or arsenocholine. However, the origin of these two compounds is not discussed, and there has been no experimental evidence to support the hypothesis. 

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