One of the initial steps in the development of therapeutic agents is the identification of lead compounds that bind to the receptor or enzyme target of interest. Many analogs of these lead compounds are then synthesized to define the key recognition elements for maximal activity. In general, many compounds must be evaluated in both the lead identification and optimization steps. Increasing burdens have been placed on these efforts due to the large number of new therapeutic targets that continue to be identified thorough modern molecular biology methods.1 To address this demand, very powerful chemical and biological methods have been developed for the generation of large combinatorial libraries of peptides2 and oligonucleotides3 that are then screened against a receptor or enzyme to identify high-affinity ligands or potent inhibitors, respectively. While these studies have clearly demonstrated the power of library synthesis and screening strategies, peptides and oligonucleotides generally have poor oral activities and rapid in vivo clearance;4 therefore their utility as bioavailable therapeutic agents is often limited. Due to the favorable pharmacokinetic properties of many small organic molecules (<600-700 molecular weight),5 the design, synthesis, and evaluation of libraries of these compounds6 has rapidly become a major frontier in organic chemistry. Lorin A. Thompson was born in Lexington, KY, in 1970. He received the Bachelor of Science degree from the University of North Carolina, Chapel Hill, in 1992 where he worked under the guidance of Joseph Desimone. He is currently pursuing his doctorate in the laboratory of Jonathan Ellman at UC Berkeley where he is the 1994 Glaxo-Wellcome fellow. His research interests include the development of synthetic methodology for organic library construction.

/pdf/synthesis-and-applications-of-small-molecule-libraries-3n3gol8dyk.pdf

Pauson-Khand cycloadditions of polymer-linked substrates

Synthesis and Applications of Small Molecule Libraries.

Linkers for solid phase organic synthesis

Recent advances in the preparation of heterocycles on solid support: a review of the literature.

Five membered carbocycles are important building blocks for many biologically active molecules. Moreover, substituted cyclopentenones (e.g. cyclopentenone prostaglandins) exhibit characteristic biological activity. The efficiency and atom economy of the Pauson-Khand reaction render this process potentially one of the most attractive methods for the synthesis of such compounds. Although it was discovered in its intermolecular form, the scope of the intermolecular Pauson-Khand reaction has always been limited by the poor reactivity and selectivity of the alkene component. The past decade, especially the last three years, has seen concerted efforts to broaden the scope of this reaction. In this overview, we provide a comprehensive and critical coverage of the intermolecular Pauson-Khand reaction based on the reactivity characteristics of different classes of alkenes and a rationalization of successes and misfortunes in this area.

Pauson-Khand cycloadditions of polymer-linked substrates

Citations

Synthesis and Applications of Small Molecule Libraries.

Linkers for solid phase organic synthesis

Recent advances in the preparation of heterocycles on solid support: a review of the literature.

The intermolecular Pauson-Khand reaction.

Carbon-carbon bond forming solid-phase reactions

Related Papers (5)

A general and expedient method for the solid-phase synthesis of 1,4-benzodiazepine derivatives

The khand reaction

Solid-Supported Combinatorial Synthesis of Structurally Diverse β-Lactams

A Silicon-Based Linker for Traceless Solid-Phase Synthesis

"Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity.