Natural product scaffolds, examples

Figure 2 Examples of natural product scaffolds missing from commercial sources.

Derivatization of functional groups in a natural-product scaffold can also be effectively performed on the solid-phase. An example of this is the synthesis of a small compound collection (27-compounds) based on the tetrahydroquinoline scaffold. A chiral tetrahydroquinoline scaffold was synthesized in solution from 5-hydroxy-2-nitrobenzaldehyde (Scheme 4). The synthesis involved a key asymmetric aminohydroxylation step. This building block was anchored to the solid support with a Wang linker and diversity was introduced by selective deprotection and derivatization of the protected hydroxyl and amino substituents. 

There are several ways to prepare libraries of natural product derivatives on a solid phase. These include (a) total synthesis on the resin (b) derivation of supported natural products and (c) syntheses of analogs based on a natural product scaffold. This review will provide examples of all these approaches. 

Figure 11 Three examples of natural product scaffolds that have been diversified by decoration...

Scheme 21.1 Selected examples of solid phase immobilization of important natural product scaffolds for diversification.

FIGURE 5.1 Selected examples of natural product scaffolds. 

The utility of the privileged structure concept is illustrated by compound library synthesis based on the indole scaffold and the biologically active compounds resulting from that. The indole scaffold is found in natural products, like for example, the neurotransmitter serotonin (5-hydoxytriptamine, 5-HT) and in well-know drugs, like for example, the... 

Aryl indole as a G-protein-coupled receptor (GPCR) privileged scaffold. The indole ring is a premier example of a privileged scaffold. The heterocycle is present in a profusion of medicinally important natural products and pharmaceutical substances, and it is associated with an extraordinary manifold of biological... 

This is the first of two syntheses included in this chapter to highlight how natural product-based scaffolds can be attached to a resin for convenient derivatization into libraries. The other example is the synthesis of sarcodic-tyin libraries described in the next section. In both cases, interesting libraries were made with minimal development time by performing scaffold construction in solution or obtaining it from a natural source. 

Type 1 MTs, currently exclusive for oxygen atoms (OMTs), methylate hydroxyl moieties of phenylpropanoid-based compounds (Fig. 2.3). The phenylpropanoid scaffold is used as a building block for many other types of compounds in the plant. Modification of this basic unit by multiple condensation reactions yields chalcone, flavonoid, isoflavonoid, and pterocarpan skeletons, for example. Flavonoids are ubiquitous in higher plants, where they function as UV protectants,5 defense compounds,6 and stimulators of beneficial mutualistic interactions with microorganisms, insects, and other organisms.7 Isoflavonoid natural products are limited primarily to leguminous plants, where they function as pre-... 

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