Natural Product-like Combinatorial Libraries Based on Privileged Structures. 2. Construction of a 10 000-Membered Benzopyran Library by Directed Split-and-Pool Chemistry Using NanoKans and Optical Encoding

Nicolaou, K. C.; Pfefferkorn, Jeffrey A.; Mitchell, Helen J.; Roecker, Anthony J.; Barluenga, Sofía; Cao, Gengyu; Affleck, and R. L.; Lillig, John

doi:10.1021/ja002034c

Cited by 287 publications

(147 citation statements)

References 8 publications

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“…[10][11][12] Toward this end, several natural product-like templates have been tethered to a solidsupport utilizing an intramolecular, selenium-mediated cycloaddition procedure. Encouraged by their success in developing chemistry and technology to produce natural productlike libraries of oxygen-containing heterocycles and carbocyclic frameworks [13][14][15][16] and due to the potential utility of such libraries in chemical biology investigations, 17,18) they sought to expand the scope of this selenium-based solid-phase chemistry to include nitrogen-containing heterocycles.…”

Section: Selenium-based Solid-phase Chemistry To Include Nitrogen-conmentioning

confidence: 99%

Solid-phase organic synthesis of heterocyclic compounds

Izumi

2006

J. Pestic. Sci.

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The establishment of an efficient method of synthesizing heterocycles is required for the development of pharmaceuticals and agrochemicals, since many bioactive compounds have a heterocyclic ring. It is also necessary to prepare libraries of small organic compounds for investigations of function and the discovery of more bioactive compounds in pharmaceutical and agrochemical chemistry. Combinatorial and parallel synthetic methodologies provide the main driving force for the preparation of libraries for applications in the discovery of lead compounds and high-throughput medicinal chemistry within the pharmaceutical industry. [1][2][3] Many different formats of high-throughput chemistry are available and solid-phase organic synthesis (SPOS) plays a pivotal role allowing the convenient handling of large numbers of synthetic intermediates. 4,5) Since the combinatorial chemistry first appeared in the early 1990s, the way drugs are discovered has changed dramatically. The SPOS strategy has been a strong tool for high throughput synthesis and combinatorial chemistry.6-9) Synthetic intermediates are retained on the support and can be, therefore, quickly separated from the reaction mixture without extraction, concentration, and purification. SPOS is thus particularly advantageous for multi-step iterative synthesis. Various solid-phase automated synthesizers have been developed and are now commercially available. Even though several synthesizers for solution synthesis have been developed, automation is essentially easier in solid-phase synthesis than solution synthesis. In particular, the automated synthesis of peptides and oligonucleotides has allowed their facile and rapid preparation and greatly contributed to the elucidation of their functions. However, SPOS is not without its drawbacks since often extended development times are required to optimize new solid-phase chemical reactions. Actually, many laboratories have been engaged in the development of novel solidphase linking strategies and chemical technologies. This paper describes recent findings in, and a useful method for, the synthesis of heterocycle and nitrogen heterocycle compounds. Selenium-based solid-phase chemistry to include nitrogen-containing heterocyclesNicolaou and co-workers have been engaged in the development of novel solid-phase linking strategies and chemical technologies aimed at the construction of discovery-oriented, natural product-like libraries. [10][11][12] Toward this end, several natural product-like templates have been tethered to a solidsupport utilizing an intramolecular, selenium-mediated cycloaddition procedure. Encouraged by their success in developing chemistry and technology to produce natural productlike libraries of oxygen-containing heterocycles and carbocyclic frameworks [13][14][15][16] and due to the potential utility of such libraries in chemical biology investigations, 17,18) they sought to expand the scope of this selenium-based solid-phase chemistry to include nitrogen-containing heterocycles. Recently, they reported t...

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Section: Selenium-based Solid-phase Chemistry To Include Nitrogen-conmentioning

confidence: 99%

Solid-phase organic synthesis of heterocyclic compounds

Izumi

2006

J. Pestic. Sci.

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“…The integration of the NanoKan microreactors in the solid-phase method described above, allowed the rapid construction of a 10000-membered benzopyran libraries, whose constituents were obtained in quantities of 1-2 mg each. 161 In addition to these natural and natural product-like libraries based on the benzopyrans scaffold, other molecules of biological interest, which includes an aldosterone biosynthesis inhibitor and related analogues, and a phosphodiesterase IV inhibitor, were also synthesized according the selenoether linking strategy. 151 Based on the fact that many natural and designed benzopyrans that contain modifications of the pyran olefin exhibit higher and/or different activity than that of the parent molecule (ex.…”

Section: Flavonoidsmentioning

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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“…This triflates. The triflate derivatives were displaced by aminoindole 11.4 in dichloromethane after the removal functionality is contained in numerous classes of natural product-like compounds) for combinatorial synthesis of chalcones and pyranocoumarins [55][56][57][58]. products, such as flavanoids, comarins, rotenoids, stilbenoids, chromene glycosides, etc.…”

Section: Highly Functionalized Polycyclic Derivativesmentioning

confidence: 99%