Plausible biosynthetic pathway

Scheme 4 Plausible biosynthetic pathway of the seco-pseudopterosins and pseudopterosins...

Zyzzya genus [58]. The structure of prianosin A (= discorhabdin A) (52), including its absolute configuration, was unequivocally defined by X-ray analysis [54], while those of discorhabdins B (54) and D (57) were based on spectral data. The previous structures proposed for prianosins C and D [55] were revised to 2-hydroxydiscorhabdin D (56) and discorhabdin D (57), respectively [59]. A plausible biosynthetic pathway for these compounds suggests the involvement of a-amino acids tyrosine (C-l-N-9) and tryptophan (C-10-C-21) [55]. 

Scheme 1. Formation of viniferins and plausible biosynthetic pathways of some stilbene dimers...

Scheme 2. Plausible biosynthetic pathways of some stilbene tetramers...

Brasiliamides are comprised of two phenylpropane moieties and acetates. The plausible biosynthetic pathway of brasiliamides starting with the formation of diketopiperazine ring is outlined in Fig. (23). Phenylalanine and 3-methoxy-4,5-methylenedioxyphenylalanine are combined into a diketopiperazine (111). Reduction of ketones, dehydration reaction, and rearrangement of the double bond lead to intermediates 112 and 113. Acetylation of the two compounds 112 and 113 leads to brasiliamide C (106) and brasiliamide B (105), respectively. The two compounds 112... 

A plausible biosynthetic pathway to perfamine and thence to more reduced alkaloids of the haplophyllidine type involves C-prenylation of a hydroxymethoxydictamnine. 

Figure 15. Plausible biosynthetic pathway for the production of Daphtiiphyllum alkaloids.

Scheme 1. Plausible biosynthetic pathways leading to the generation of colombiasin A (1) from other natural products isolated from various members of the Pseudopterogorgia genus.

With all these elements in hands, a plausible biosynthetic pathway has been proposed, but the exact mode of connection between lysine- and tyrosine-derived precursors remains unknown (Scheme 44). 

Along with the structural elucidation of nirurine (45), Cordell and coworkers proposed a plausible biosynthetic pathway leading to this compound (Scheme 46). One of the key features of this mechanism was the involvement of a dopamine-building block instead of the usual tyrosine precursor for the elaboration of the CD rings. Thus, the cormection of ornithine unit (266) to dopamine (267) could give rise to intermediate 268 after butenolide formation. Then, attack of the nitrogen to the carbonyl moiety followed by reduction of the C8—C9 double bond and elimination of a molecule of water would furnish compound 43. Finally, a nucleophilic attack of the C8—OH onto the corresponding C5—N1 iminium ion of 43 would deliver nirurine (45). 

A plausible biosynthetic pathway to madangamines from partially reduced bis-3-alkylpyridine macrocydes is outlined in Scheme 3. A distinguishing... 

SCHEME 5 Conversion of vibsanin C (2) to vibsanin E (16) and a plausible biosynthetic pathway for cyclovibsanins. 

SCHEME 10 Plausible biosynthetic pathways for the formation of various neovibsanins from vibsanin B (1). 

Whole-cell feeding experiments imply adding labeled putative precursors (radioactive or stable isotope label) to the whole organism, which is grown on a synthetic media. The products and intermediates are then isolated, purified, and analyzed by the various methods. This type of experiment enables one to propose a plausible biosynthetic pathway. Isolation and purification of the enzymes responsible for each step of the pathway enable verification at the enzymatic level. The in vitro conversion of a putative precursor by the pure enzyme to the product constitutes unambiguous proof of the biosynthetic reaction. The ultimate proof of a biosynthetic pathway depends, therefore, on the characterization of the enzymes involved in each step of the pathway. The only major drawback is that the procedure is extremely difficult, and the detailed enzymology for polyketide-derived eompounds deserves further study. The problems are (a) instability of the enzymes, (b) lack of reproducibility, and (c) variability of activity in different enzymatic preparations (some of these enzymes are membrane bound and easily deactivated by isolation). Despite the difficulties involved, some of the enzymes involved in the biosynthesis of patulin and penicillic acid have been partially purified and characterized. 

The proliferation in the number of new and diverse fungal metabolites in recent years complicates a comprehensive survey of their biogenetic origin. The biosynthesis of many metabolites appears to be trivial, because a cursory chemical inspection of the structure allows the formulation of a plausible biosynthetic pathway. For many new metabolites, no toxicological data are available and only the structural elucidation together with a biosynthetic postulate is reported. Thus the biosynthetic origin of viridicatumtoxin (1), a toxic metabolite from Penicillium viridicatum (Kabuto et al., 1976), has not been studied, but is most probably closely modeled on that of the tetracyclines (McCormick, 1967). Similarly, verruculotoxin (2), isolated from cultures of Penicillium verruculosum, is most probably derived from two L-amino acids, phenylalanine and pipecolic acid (Macmillan et aL, 1976). 

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