Structural Classification of Natural Products

KochMA, SchuffenhauerA, ScheckM, etfl/. (2005) Charting biologically relevant chemical space A structural classification of natural products (SCONP). Proc. Natl. Acad. Set. 102 11111-11211. 

B. The scaffold tree for structural classification of natural products... 

Koch, M. A., Schuffenhauer, A., Scheck, M., Wetzel, S., Casaulta, M., Odermatt, A., Ertl, P, and Waldmann, H. (2005) Charting biologically relevant chemical space A structural classification of natural products (SCONP). Proc. Natl. Acad. Sci. U.S.A. 102,17272-17277. 

For compound sets with a well defined limit, it is possible to enumerate all the scaffolds in the set and to visualise the chemical relationships. In particular, the Bioactivity guided Scaffold tree method (BIOS) provides a visually compelling means of exploring complex structural relationships. As an example, the Structural Classification of Natural Products (SCONP) arranges the scaffolds of the natural products in this tree-like fashion. This provides a concise and chemistry friendly description of natural product diversity. 

Figure 14.2 The Scaffold tree visualisation of the Structural Classification of Natural Products (SCONP). Reproduced from ref. 61, Waldman et al., Proc. Natl. Acad. Sci. 2005, 102, 17272. Copyright 2005 National Academy of Sciences, U.S.A.

The molecular scaffolds (ring systems) validated by nature or biology can be arranged into hierarchical clusters Structural Classification of Natural Products (SCONP) (Figure 1.2), which could accelerate the design... 

Waldmann et al. have performed a chemoinformatic analysis of all available natural product structures and classified fhe most frequent occurring scaffolds in a hierarchical tree (Structural Classification of Natural Products, SCONP) [115]. This analysis represenfs for fhe first time a quantitative description of privileged structures found among natural products. The Wald-... 

Two chapters in section five describe different aspects of the biosynthesis of polyketides, which are numerically the most abimdant and structurally diverse class of natural products. The first chapter reports in vivo and in vitro studies aimed at enhancing our understanding of the basic pathways of polyketide assembly with a view to producing novel compounds. In the second chapter, a consistent difference in the modes of cyclisation of the fused ring polyketides of fungi and streptomycetes is described, which provides the basis for a new biosynthetic classification of these metabolites. 

The ketone functional group appears in a wide variety of natural products ranging from the simple terpenes to complex macrocycles and polyfunctional molecules. This section will focus on simple, naturally-occurring ketones, largely from the terpene family, which illustrate relationships between structure and 1 0 NMR chemical shifts. Other more complex ketone containing structures will be examined later according to their natural product family classification, e.g. chromones, flavones, etc. 

The diterpenoids are a large and ubiquitous family of isoprenoids derived from 2E,61% ] 0 -geranylgeranvl pyrophosphate. Of all the families of natural products, the diterpenoids have one of the widest ranges of biological activity. The clearest classification of the cyclic diterpenoids (abietane, labdane, clerodane,...) is based on biogenetic considerations. The variety of structural types found amongst the diterpenoids has led to their use as phytochemical markers. Indeed, many of the diterpenoids found in recent years have been isolated in the course of phytochemical surveys of the Compositae. 

Comprehensive examinations of the structures of many natural products and their chemical compositions to further industrial utilization of annually renewable resources have been reported. Earlier research and development work can be extended to yield new industrial products, particularly in modifying the properties of natural products to give currently desired properties, as reported in this symposium. A classification of important structures to be considered is outlined. 

---