Natural product scaffold tree

FIGURE 9.12 Structural motifs identified in the natural product scaffold tree and used as templates for natural product-based compound collections. 

FIGURE 9.10 Tree-like graphical representation of natural product scaffolds. For clarity, only scaffolds that cumulatively represent at least 0.2% of the natural products in the DNP are shown. 

Various N-alkylated derivatives of amino acids are natural products [e.g., H-D-(Me)Tyr-OH (D-surinamine) and H-(Me)Trp-OH (abrin) were found in cabbage tree bark1691] and many of them are used as enzyme inhibitors, receptor agonists and antagonists, building blocks for heterocyclic scaffolds in combinatorial chemistry, etc. In this section the preparation of N-alkyl amino acids in solution for their use in peptide synthesis is described. This implies that the synthetic procedures described in this section will ultimately result in V-alkyl amino acids appropriately protected for peptide synthesis. 

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

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.

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-... 

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