Biogenesis of natural products

A fascinating area of research linking organic chemistry and biology is the study of the biogenesis of natural products the detailed sequence of reactions by which a compound is formed in living systems, plant or animal. All the isoprene units in nature, it appears, originate from the same compound, isopentenyl pyrophosphate. 

Barton and Cohen 10) and Erdtman and Wachtmeister 11) have related the concept of free radical coupling of phenols to the biogenesis of natural products, and suggested that bisbenzylisoquinoline alkaloids are formed by this reaction from benzylisoquinoline units. The mechanism of the reaction consists of generation of the resonance-stabilized phenoxy free radical by one-electron oxidation of the phenoxy anion, followed by coupling and tautomerization to form hydroxylated diphenyls or diphenyl ethers. Intermolecular coupling may involve any... 

Mattoon, J. R. In P. Bernfeld, Biogenesis of Natural Products, S. 1. Oxford Pergamon Press 1963. 

Besides the use of chiral amines to activate nucleophiles via enamine formation, their use as acceptor-activating catalysts via iminium formation has resulted in the development of numerous impressive applications over the last decade. The concept of iminium activation of conjugated enones has been postulated to play a pivotal role in the biogenesis of natural products as proposed by Baldwin et al. for the key Diels-Alder step in e.g. the biosynthesis of himgravine 188-190). 

Bernfeld, P. (Ed.) Biogenesis of Natural Products, Pergamon Press, 1964. 

Examination of the charts in Chapters 6.1.1 to 6.1.3 shows that the American and eastern tropical areas contribute more that the African tropics to the diversity of natural products. In particular the African tropics are poor in terpenoids, except secologanin, which is involved on a world basis in the formation of mixed-biogenesis alkaloids. 

The term meroterpenoids is generally used to denote a wide range of natural products of mixed (polyketide-terpenoid) biogenesis [121]. In our laboratory, the titanocene-catalyzed 6-endo/6-endo cyclization of 31, ob-... 

A resurgence of interest and accomplishment in the field of biosynthe sis of natural products - including antibiotics - has occurred. The powerful methods for determination of a new structure with small amounts of material (mass and nmr spectroscopy, etc.) together with the development of 13C nmr spectroscopy for following the pattern of incorporation of precursors into these structures is one major reason. The subject of biogenesis of antibiotics has not been dealt with specifically in this series and this brief review will include some literature from earlier years than 1976. 

The book by Mann et al. (1994) on natural products provides a good introduction to the biogenesis of natural perfume ingredients and the review by Croteau (1987) gives further detail on the biosynthesis of monoterpenes. 

Despite their great structural variety, isoquinoline alkaloids were, for a long time, considered as a vast, but biosynthetically uniform family of natural products, the common key step of their biogenesis always being the Mannich-type condensation of phenylethylamines with aldehydes or a-ketoacids (7). The preparative imitation of this reaction principle, the Pictet-Spengler-type isoquinoline synthesis (2), has been the basis for countless biomimetic alkaloid syntheses (5). 

The chemistry of natural products encompasses their isolation, structure elucidation, partial and total synthesis, elucidation of their biogenesis, and the biomi-metic synthesis of N. p. Major breakthroughs in analysis were, e.g., the structural clarifications of morphine, lignin, insulin, estrones, and cholesterol as well as the elucidation of the biosyntheses of terpenoids, morphine, penicillin, chlorophyll, and vitamin B 2. Major advances in synthetic chemistry were, e.g., the total syntheses of camphor, hemin, quinine, saccharose, tropine, stryehnine, chlorophyll, vitamin B 2, erythromycin, taxol and palytoxin. Numerous N. p. of the so-ealled ehiral pool are used as starting materials for the synthesis of optically active compounds or serve (in the form of their derivatives) as catalysts for enantioselective syntheses. 

Williams, R. T. The biogenesis of conjugation and detoxication products. In Biogenesis of Natural Compounds (P. Bernfeld, ed.), pp. 589-639. Pergamon Press, Oxford 1967... 

Rosenthal, G. A., Bell, E. A. Naturally occurring, toxic nonprotein amino acids. In Herbivores, Their Interaction with Secondary Plant Metabolites (G. A. Rosenthal, D. H. Janzen, eds.), pp. 353-385. Academic Press, New York 1979 Smith, R. L. The Excretory Function of Bile. Chapman and Hall, London 1973 Williams, R. T. The biogenesis of conjugation and detoxication products. In Biogenesis of Natural Compounds (P. Bernfeld, ed.), pp. 589-639. Pergamon Press, Oxford 1967... 

As a further consequence of the recent discoveries in the field of biogenesis as previously outlined, it is now apparent that terpenoids and their derivatives do, in fact, occupy a position in modern clinical practice completely in keeping with their stature as one of the major groups of natural products, and that the earher tendency to regard them as something in the nature of curiosities in the realm of therapeutic agents must now be retracted. 

Similarities in structure commonly reflect similarities in biogenesis. Consideration of the architectural patterns and structural relationships of natural products enabled Collie, Robinson, Ruzicka and others to discern the biogenetic units from which certain phenolic compounds, alkaloids and terpenes were formed. A survey of the antibiotics indicates that one large collection of these substances can be derived mainly from amino acid residues, another mainly from acetate (or, on occasion, propionate) and a third from simple sugars. Some structures can be dissected into two or more different fragments that are derived from different types of biogenetic unit. 

In this chapter, some of the latest developments in the groups of natural products collectively known as the quinolin/one, quinazolin/one, and acridone alkaloids are presented. Emphasis is placed on their biogenesis, biological activities, and... 

The vast array of natural products produced from these simple building blocks can only be viewed with considerable awe. The chemistry involved in isolation, proof of structure, synthesis, and tracing the biogenesis includes some of the most impressive chemistry of this century. But we also need to stand in awe of Nature wherein natural selection has led to the elaboration of ever more complex natural products to protect the tree and promote survival. These extractives have a long history of serving humankind where no synthetic substitute existed. 

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