{"id":4217,"date":"2023-09-28T08:28:03","date_gmt":"2023-09-28T06:28:03","guid":{"rendered":"https:\/\/ospt.osi.lv\/2023\/09\/28\/macrocyclic-peptidomimetic-plasmepsin-x-inhibitors-with-potent-in-vitro-and-in-vivo-antimalarial-activity-2\/"},"modified":"2023-11-10T12:05:15","modified_gmt":"2023-11-10T10:05:15","slug":"macrocyclic-peptidomimetic-plasmepsin-x-inhibitors-with-potent-in-vitro-and-in-vivo-antimalarial-activity-2","status":"publish","type":"post","link":"https:\/\/ospt.osi.lv\/macrocyclic-peptidomimetic-plasmepsin-x-inhibitors-with-potent-in-vitro-and-in-vivo-antimalarial-activity-2\/","title":{"rendered":"47. Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N-Acetylamino Malonic Acid Derivatives"},"content":{"rendered":"<div class=\"wpb-content-wrapper\"><p>[vc_row][vc_column][vc_column_text]Koleda O., Prane K., Suna E. <em>Org. Lett.<\/em> <strong>2023<span class=\"cit-volume\">, <\/span><\/strong><span class=\"cit-volume\"><em>25 (<\/em><\/span><span class=\"cit-issue\">44)<\/span><span class=\"cit-pageRange\"><em>,<\/em> 7958\u20137962<\/span>.<br \/>\nDOI: <a href=\"https:\/\/doi.org\/10.1021\/acs.orglett.3c02687\">https:\/\/doi.org\/10.1021\/acs.orglett.3c02687<\/a>.<\/p>\n<p>&nbsp;<\/p>\n<p><!--more--><\/p>\n<h4>Abstract<\/h4>\n<p style=\"text-align: justify;\">Broad application of \u03b1,\u03b1-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing amino acid derivatives that relies on anodic decarboxylation-intramolecular etherification of inexpensive and readily available <i>N<\/i>-acetylamino malonic acid monoesters under Hofer\u2013Moest reaction conditions. The decarboxylative cyclization proceeds under constant current conditions in an undivided cell in an aqueous medium without any added base. A successful bioisosteric replacement of the 1-aminocyclohexane-1-carboxylic acid subunit by the THP-containing amino acid scaffold in cathepsin K inhibitor balicatib helped to reduce lipophilicity while retaining low nanomolar enzyme inhibitory potency and comparable microsomal stability.<\/p>\n<p>[\/vc_column_text][\/vc_column][\/vc_row]<\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>[vc_row][vc_column][vc_column_text]Koleda O., Prane K., Suna E. Org. Lett. 2023, 25 (44), 7958\u20137962. DOI: https:\/\/doi.org\/10.1021\/acs.orglett.3c02687. &nbsp;<\/p>\n","protected":false},"author":5,"featured_media":4219,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"image","meta":{"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[43,16],"tags":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts\/4217"}],"collection":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/comments?post=4217"}],"version-history":[{"count":4,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts\/4217\/revisions"}],"predecessor-version":[{"id":4246,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts\/4217\/revisions\/4246"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/media\/4219"}],"wp:attachment":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/media?parent=4217"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/categories?post=4217"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/tags?post=4217"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}