Sukhdev Manku

ADVERTISEMENT RETURN TO ISSUEReviewNEXTSolution- and Solid-Phase Strategies for the Design, Synthesis, and Screening of Libraries Based on Natural Product Templates: A Comprehensive SurveyDennis G. Hall, Sukhdev Manku, and Fan WangView Author Information Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2 Canada Cite this: J. Comb. Chem. 2001, 3, 2, 125–150Publication Date (Web):February 8, 2001Publication History Received20 November 2000Published online8 February 2001Published inissue 1 March 2001https://pubs.acs.org/doi/10.1021/cc0001001https://doi.org/10.1021/cc0001001review-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1523Altmetric-Citations165LEARN 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 options SUBJECTS:Cells,Genetics,Mixtures,Organic polymers,Pharmaceuticals Get e-Alerts

A mild oxidative workup protocol using iodine in an acetic acid-acetate buffer solution is described for the cleavage of borane-amine adducts arising from the borane-promoted reduction of polyamides supported onto practical trityl-based resins. Chiral polyamines with diverse side-chain functionalities can be generated as free bases without premature release from the solid support and with essentially no racemization using this method. A series of model oligomeric secondary diamides 6 containing various alpha-amino acid residues (Val, Phe, Tyr, Ser, Cys, Met, Gln, Trp) provided triamine products 8 in high yields and good to excellent purity. On the other hand, a substrate containing a tertiary amide (15) formed a rather unusual triaminoborane intermediate that required more stringent workup conditions to liberate the polyamine product 20. The reduction of oligomeric tertiary amides such as 9 was found sluggish, but these compounds could nonetheless be obtained in high purity from in situ reductive amination of the corresponding secondary amines. Control studies, carried out in solution with model secondary amide 23, confirmed the efficiency of the buffered iodine solution and highlighted several advantages (no heating necessary, no need for strong bases or acids) over existing methods for the cleavage of borane-amine adducts. A possible mechanism involving all buffer components (iodine, acetic acid, and acetate ion) is proposed in which borane-amine adducts are transformed first to the monoiodoborane-amine and then to the corresponding acetoxyborane-amine adduct of much weaker coordination affinity. The latter would dissociate readily and get trapped by the acetic acid to provide the desired secondary amine. This reduction/oxidative workup protocol is useful as a general method for the facile solid-phase synthesis of polyamines for eventual release in solution and use in various applications. It is also potentially very useful toward the synthesis and screening of bead-supported libraries of free oligoamines assembled through split-pool methods.