Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ Alexander E. Sorochinsky, Santos Fustero,*,‡,§ Vadim A. Soloshonok,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andreś Estelleś, 46100 Burjassot, Valencia, Spain Laboratorio de Molećulas Orgańicas, Centro de Investigacioń Príncipe Felipe, C/ Eduardo Primo Yuf́era 3, 46012 Valencia, Spain Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine

Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

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.

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Synthesis and Applications of Small Molecule Libraries.

1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

Cloning and characterization of the

Les enolates de titane sont prepares a partir des precurseurs carbonyles correspondants avec TiCl 4 et une amine tertiaire, dans des conditions douces

New procedure for the direct generation of titanium enolates. Diastereoselective bond constructions with representative electrophiles

or a decrease in the aggregation of silyl ion pairs in the presence of THF. Polymerization in a mixture of benzene (40%) and THF (60%) is completed within less than 2 min at the same initiator concentration as shown in Figure 1 . However, after 1 h, nearly all polymer has been degraded to cyclopentaand cyclohexasilanes. Polymerization in pure T H F yields only cyclics. Polymerization is completed within seconds in benzene in the presence of equimolar amounts of cryptands ([2.2.2] for silylpotassium and [2.1. I ] for butyllithium); however, in contrast to THF, no depolymerization was observed within 24 h. Thus, the polarity and solvation power of a reaction mixture influences propagation, macrocyclization, and termination. There are three important regions in the methyl group area of the 'H NMR spectrum. The most deshielded region (>0.6 ppm) corresponds t o four-membered rings. The relative reactivities of the isomers must be similar, since the peak intensities do not change during polymerization. The most shielded region (down to -0.6 ppm) corresponds to poly(methylphenylsilylene). Relative intensities of three broad peaks, assigned to iso-, hetero-, and syndiotactic structure^,'^ remain similar during polymerization. The sharp signals in the intermediate region are due to cyclopenta-

Fèlix Urpí

Papers

New procedure for the direct generation of titanium enolates. Diastereoselective bond constructions with representative electrophiles

Stereoselective aldol reactions of chlorotitanium enolates. An efficient method for the assemblage of polypropionate-related synthons

Synthesis of six-membered oxygenated heterocycles through carbon-oxygen bond-forming reactions

A fast procedure for the reduction of azides and nitro compounds based on the reducing ability of Sn(SR)3-species

New synthetic “tricks”. Triphenylphosphine-mediated amide formation from carboxylic acids and azides