Natural product-like libraries

Soldi AM. Libraries from natural product-like scaffolds. Curr Opin Chem Biol 2004 8 281-6. 

Scheme 3.32 Prototypical structures for the synthesis of natural product-like libraries.

Abreu PM, Branco PS. (2003) Natural product-like combinatorial libraries. J Braz Chem Soc 14 675-712. 

Boldi AM. (2004) Libraries from natural products-like scaffolds. Curr. Opin. Chem. Biol. 8 281-286. 

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... 

Ertl, P., Roggo, S. and Schufienhauer, A. (2008) Natural product-likeness score and its application for prioritization of compound libraries. Journal of Chemical Information and Modeling, 48, 68-74. 

Nicolaou, K.C. Pfefferkom, J.A. Barluenga, S. Roecker, A.J. Cao, G.-Q. (2000C) Natural product-like combinatorial libraries based on privileged structures. 3. The libraries from libraries principle for diversity enhancement of benzopyran libraries. J. Am. Chem. Soc., 122, 968-76. 

Two strategies have emerged for the synthesis of natural-product-like libraries on solid. The first involves building the entire core structure on solid support, a very challenging proposi-... 

A discussion to the concept of natural product-like combinatorial libraries based on privileged structures and an impressive experimental proof of concept has been disclosed by the Nicolaou group a) K. C. 

After the advent of combinatorial chemistry and its lack of success, it was recognised that the combinatorial libraries lacked diversity. Hence, new approaches were applied to design compounds that allowed the introduction of many points of diversity, such as chiral centres to mimic natural products.6 These libraries are also called natural product-like libraries.7... 

Several attempts have also been reported to integrate natural products and combinatorial synthesis, either by using natural products as scaffolds for combinatorial modification or by building libraries of natural product-like... 

The selection and quality of a screening library with drug-like and lead-like structures is a critical endeavour. The features of drug-like and lead-like structures continue to be better defined, at the same time as the diversity of drug-like and lead-like molecular space continues to be explored and categorised. Other areas of development focus on the discovery of small molecules suitable for modulating protein-protein interactions, with a greater focus on natural product-like compounds. 

A combinatorial natural-product-like and diversity-orientated library of 10 000 benzopyran-based small molecules was constructed by Nicolaou and coworkers [74, 75]. They chose a solid-phase approach and an anchoring strategy that does not limit complexity building operations (Scheme 14.11). They used a polystyrene-based selenyl bromide resin (43) on which substrates can be immobilized by electrophilic cyclization reactions. Here, ortho-prenylated phenol 44 was reacted with the selenyl bromide (43) to form the benzopyran scaffold (45) via a 6-endo-trig cyclization. 

Scheme 14.11 Solid-phase synthesis of a benzopyran-based natural-product-like combinatorial library.

The first part of the chapter covers several examples of stereoselective solution and solid-phase approaches to obtaining natural product analogs. The examples discussed here represent focused strategies to library generation that are based on specific bioactive natural products. These libraries have often served as natural product analogs in searches for better biological responses than those exhibited by the parent natural products. The generation of libraries of natural product-like compounds by solution and solid-phase synthesis methods is discussed in the second half. 

Diversity-oriented Synthesis of Natural-product-like Libraries... 

Fig. 17.13 The use oftetrahydroaminoquinoline and aminoindoline scaffolds in the library generation of natural product-like compounds and in silico testing of these two libraries as small molecule binders to Bcl-2/Bcl-XL...

In collaboration with the Gehring laboratory, the tetrahydroaminoquinoline and aminoindoline-derived natural product-like libraries, and several related... 

From Natural Products to Natural Product-Like Libraries - Hubris or Progress ... 

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