Soluble-Polymer Supported Synthesis of a Prostanoid Library:  Identification of Antiviral Activity

Lee, Kyung Joo; Angulo, Ana; Ghazal, Peter; Janda, Kim D.

doi:10.1021/ol991130j

Cited by 54 publications

(28 citation statements)

References 16 publications

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“…Examples of libraries based on natural products scaffolds. A library based on prostaglandins yielded compound 7aa, a novel antiviral compound [35]. A library based on prostaglandins yielded compound 7aa, a novel antiviral compound [35].…”

Section: Synthesis Of Natural Products Librariesmentioning

confidence: 99%

Chemical and Biological Integrity in Natural Products Screening

Harrigan¹,

Goetz²

2005

CCHTS

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Due to pressure from combinatorial chemistry and the streamlining of the drug discovery process through automated high-throughput screening technologies, pharmaceutically based natural products programs are under increasing scrutiny. However by taking advantages of technologies originally developed for high-throughput screening and combinatorial chemistry and applying them to processes considered as bottlenecks in classical natural products chemistry (purification, structure elucidation, sample availability) it is our opinion that natural products can still contribute to the effective discovery of novel bioactive and pharmaceutically relevant metabolites. We describe here several such strategies that if universally implemented, will demonstrate i) whether chemical diversity is truly being accessed, ii) that novel metabolites can be formatted in a manner appropriate for modern screening paradigms, and iii) that natural products can be rapidly identified not only for novelty and pharmaceutical relevance but to assess their true biological origin.

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Section: Synthesis Of Natural Products Librariesmentioning

confidence: 99%

Chemical and Biological Integrity in Natural Products Screening

Harrigan¹,

Goetz²

2005

CCHTS

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“…Using a parallel-pool library strategy, the same research team prepared a library of 16 prostaglandin derivatives distributed in four pools, each containing a constant α-side-chain with four different ω-side-chains resulting from the Noyori's reaction. 83 Some of these prostaglandin analogues, as compounds 17a-d, have proved to inhibit the growth of the herpes-family virus CMV on infected murines.…”

Section: Fatty Acids Derivativesmentioning

confidence: 99%

Natural Product‐Like Combinatorial Libraries

Abreu

Branco

2004

ChemInform

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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.

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“…Contrary to the use of cross‐linked polystyrenes, and of macropores, non‐cross‐linked polystyrene copolymer supports have been introduced to overcome the restricted access to active sites 24. These polymers are soluble in most organic solvents but precipitate in certain cooled solvents, for example, methanol 25, 26. This development is in line with the use of other soluble polymers and in particular soluble poly(ethylene glycol) (PEG)27 in polymer‐supported synthesis.…”

Section: Polymer Supportsmentioning

confidence: 99%

Functionalized Polymers-Emerging Versatile Tools for Solution-Phase Chemistry and Automated Parallel Synthesis

Kirschning

Monenschein

Wittenberg

2001

Angew. Chem. Int. Ed.

379

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As part of the dramatic changes associated with the need for preparing compound libraries in pharmaceutical and agrochemical research laboratories, industry searches for new technologies that allow for the automation of synthetic processes. Since the pioneering work by Merrifield polymeric supports have been identified to play a key role in this field however, polymer‐assisted solution‐phase synthesis which utilizes immobilized reagents and catalysts has only recently begun to flourish. Polymer‐assisted solution‐phase synthesis has various advantages over conventional solution‐phase chemistry, such as the ease of separation of the supported species from a reaction mixture by filtration and washing, the opportunity to use an excess of the reagent to force the reaction to completion without causing workup problems, and the adaptability to continuous‐flow processes. Various strategies for employing functionalized polymers stoichiometrically have been developed. Apart from reagents that are covalently or ionically attached to the polymeric backbone and which are released into solution in the presence of a suitable substrate, scavenger reagents play an increasingly important role in purifying reaction mixtures. Employing functionalized polymers in solution‐phase synthesis has been shown to be extremely useful in automated parallel synthesis and multistep sequences. So far, compound libraries containing as many as 88 members have been generated by using several polymer‐bound reagents one after another. Furthermore, it has been demonstrated that complex natural products like the alkaloids (±)‐oxomaritidine and (±)‐epimaritidine can be prepared by a sequence of five and six consecutive polymer‐assisted steps, respectively, and the potent analgesic compound (±)‐epibatidine in twelve linear steps ten of which are based on functionalized polymers. These developments reveal the great future prospects of polymer‐assisted solution‐phase synthesis.

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Soluble-Polymer Supported Synthesis of a Prostanoid Library: Identification of Antiviral Activity

Cited by 54 publications

References 16 publications

Chemical and Biological Integrity in Natural Products Screening

Chemical and Biological Integrity in Natural Products Screening

Natural Product‐Like Combinatorial Libraries

Functionalized Polymers-Emerging Versatile Tools for Solution-Phase Chemistry and Automated Parallel Synthesis

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