Fluorine substitution is a highly effective approach for altering the chemical properties of compounds that affect the biological activity and pharmacological distribution of numerous drugs, including anti-depressants, anti-inflammatory agents, anti-psycho-tics, steroids, antivirals and anesthetics [1]. Given the importance of small molecule combinatorial libraries in the process of drug design, we decided to explore the synthesis of fluorinated compounds using solid-phase chemistry. The Reformatsky reaction with ethyl bromodifluoroacetate is commonly used for the incorporation of the-CF2CO- group [2], Katrizky et al. [3] successfully developed the Reformatsky reaction of bromofluoroacetates with N-(α-aminoalkyl)benzotriazole in solution, and showed its utility in the synthesis of difluoro-β-amino esters. Herein, we describe the solid-phase Reformatsky reaction of ethyl bromodifluoroacetate and a polymer-supported imine for the parallel synthesis of α-difluoro-β-amino acids.

Solid phase synthetic approaches enable the preparation of large numbers of new biologically interesting compounds. Small molecule libraries of heterocycles have proven effective for the identification of various bioactive compounds [1]. 4-Imidazolidinones belong to a group of biologically interesting and less-explored heterocyclic compounds. This type of molecule was identified as a product of a spontaneous cyclization of N-terminal amino groups of peptides or proteins, with formaldehyde, acetone or acetaldehyde in aqueous solutions [2]. N-terminal 4-imidazolidinones derivatives of proteins or peptides were also identified in the human liver during chronic ethanol oxidation [3]. The same type of modification was used to form enzymatically stable prodrugs based on peptides [4].

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTSolid-Phase Synthesis of α,α-Difluoro-β-amino Acids via the Reformatsky ReactionAgnès Vidal, Adel Nefzi, and Richard A. HoughtenView Author Information Torrey Pines Institute for Molecular Studies, San Diego, California 92121 [email protected]Cite this: J. Org. Chem. 2001, 66, 24, 8268–8272Publication Date (Web):November 3, 2001Publication History Received27 August 2001Published online3 November 2001Published inissue 1 November 2001https://pubs.acs.org/doi/10.1021/jo010872zhttps://doi.org/10.1021/jo010872zbrief-reportACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views590Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aldehydes,Fluorine,Monomers,Peptides and proteins,Reagents Get e-Alerts

Tritiated leukotriene A(4) and 8-epi-prostaglandin F-2 alpha methyl esters were prepared from the corresponding acetylenic precursors by selective reduction with tritium gas to provide a probe for the metabolite identification of these oxylipins. Partially deactivated Pd-catalysts were prepared from commercial products and their composition was optimized to achieve the better selectivity. A micro-method for the saponification of labelled oxylipins methyl esters was used.

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Different (omega-1)-functionalized phosphonium ylides 5 were obtained from commercially available 5-chloropentan-2-one 3 and but-3-yn-1-ol 4 in several steps. Some of the phosphonium ylides obtained were coupled using a Wittig reaction with a chiral epoxydienal 1 (prepared from (-)-2-deoxy-D-ribose 2 as starting material) to afford (omega-1)-functionalized leukotriene A(4) (LTA(4)) methyl ester analogues. The described strategy demonstrates a general and flexible approach to other leukotriene analogues stable to beta-oxidation, and/or molecular probes carrying reporter groups to characterize a potential LTC4 receptor.