Natural product-like combinatorial libraries

Abstract

A química combinatorial emergiu ao longo dos últimos anos como uma importante ferramenta na pesquisa de moléculas pioneiras para a modelagem de novos fármacos. Nesta perspectiva, a diversidade estrutural e a vasta gama de propriedades biológicas exibidas pelos metabolitos secundários, constituem um desafio à implementação de estratégias combinatórias na síntese e derivatização de produtos naturais. Este artigo ilustra a aplicação das técnicas combinatórias no desenho e formação de bibliotecas baseadas em produtos naturais de diversa origem biossintética, e seus análogos estruturais.Combinatorial chemistry has emerged over the last few years as an important tool for drug discovery and lead optimisation. In this approach, the molecular diversity and range of biological properties displayed by secondary metabolites constitutes a challenge to combinatorial strategies for natural products synthesis and derivatization. This article surveys the application of combinatorial techniques to the design of "natural product-looking" libraries covering a wide range of structural diversities.

Natural Products in Drug Discovery: Impacts and Opportunities — An Assessment

“…Natural products have been used also as starting templates in the synthesis of combinatorial libraries. 92,[106][107][108][109][110] Natural product pharmacophores are well represented in lists of "privileged structures", which make them ideal candidates for building blocks for biologically relevant chemical libraries. 111,112 Natural products still constitute a prolific source of novel lead compounds or pharmacophores for medicinal chemistry, and hence, natural products should be incorporated into a well-balanced drug discovery program.…”

Advances in Solution- and Solid-Phase Synthesis toward the Generation of Natural Product-like Libraries

“…Parallel to this approach, the goal of DOS is to populate the unexplored chemical space by developing methods that allow rapid access to natural product-like compounds having three-dimensionally complex architectures. 1,[70][71][72][73][74][75][76][77][78][79][80][81][82][83] In addition to generating the libraries of natural product derivatives, interest is also growing in developing methods for obtaining bioactive natural product-inspired scaffolds. These scaffolds could then be utilized in the library generation protocols.…”

Charting Biological and Chemical Space: PSSC and SCONP as Guiding Principles for the Development of Compound Collections Based on Natural Product Scaffolds

“…For example, Ley and co-workers have extensively used polymer-supported reagents and scavengers in the total synthesis of epothilone C and other natural products [17]. A variety of libraries derived from natural products such as carbohydrates, steroids, fatty acid derivatives, polyketides, peptides, terpenoids, flavonoids and alkaloids has been designed and synthesized in recent years (for representative examples, see Figure 1) [18,19]. Strategies for the exploitation of natural products in compound library synthesis on solid supports have been reviewed recently [19,20].…”