{"id":13457,"date":"2018-04-14T12:11:00","date_gmt":"2018-04-14T12:11:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&p=13457"},"modified":"2026-01-30T12:15:13","modified_gmt":"2026-01-30T12:15:13","slug":"diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/","title":{"rendered":"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds"},"content":{"rendered":"\n

Dr. Steven M. Wales,\u00a0Dr. Elena G. Merisor<\/strong>,\u00a0Dr. Holly V. Adcock<\/strong>,\u00a0Dr. Christopher A. Pearce<\/strong>,\u00a0Dr. Ian R. Strutt<\/strong>,\u00a0Dr. William Lewis,\u00a0Dr. Daniel Hamza<\/strong>,\u00a0Prof.\u2005Dr. Christopher J. Moody<\/p>\n\n\n\n

Abstract<\/strong><\/p>\n\n\n\n

A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable 2-aryl, 3-carboxy and 4-amino substituents, has been prepared for biological evaluation within the European Lead Factory. Diastereoselective reductive amination of pre-functionalised 4-oxofurans, readily prepared from cinnamate esters via oxa-Michael\/Dieckmann annulation, provided the requisite THF cores on gram scale with three contiguous stereocentres, including full substitution at C-3. In a second series, a pyrrolidine ring was fused to the same oxofuran scaffold via an intramolecular reductive amination, inverting the configuration at C-4 relative to the other ring substituents. The resulting compounds, which displayed desirable physical properties as lead-like scaffolds, were derivatised into a small library of 24\u2005compounds, demonstrating their ability to serve as starting points for drug discovery. Ultimately, this chemistry enabled the preparation of 1948 THF-containing compounds for inclusion in the Joint European Compound Library.<\/p>\n\n\n\n

Ref: Chemistry 2018<\/a><\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"template":"","category":[682,714],"resource_tag":[],"class_list":["post-13457","journal-paper","type-journal-paper","status-publish","hentry","category-chemistry","category-synthetic-chemistry"],"acf":[],"yoast_head":"\nDiastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds - Sygnature<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds - Sygnature\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/\" \/>\n<meta property=\"og:site_name\" content=\"Sygnature\" \/>\n<meta property=\"article:modified_time\" content=\"2026-01-30T12:15:13+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/sygnature-hit-to-lead-team-collaboration-scaled.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"2560\" \/>\n\t<meta property=\"og:image:height\" content=\"1707\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Estimation du temps de lecture\" \/>\n\t<meta name=\"twitter:data1\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\\\/\",\"name\":\"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds - Sygnature\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#website\"},\"datePublished\":\"2018-04-14T12:11:00+00:00\",\"dateModified\":\"2026-01-30T12:15:13+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\\\/#breadcrumb\"},\"inLanguage\":\"fr-CA\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/page-daccueil\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#website\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/\",\"name\":\"Sygnature Discovery\",\"description\":\"\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#organization\"},\"alternateName\":\"Sygnature\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"fr-CA\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#organization\",\"name\":\"Sygnature Discovery\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"fr-CA\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2025\\\/11\\\/Logo.svg\",\"contentUrl\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2025\\\/11\\\/Logo.svg\",\"width\":1,\"height\":1,\"caption\":\"Sygnature Discovery\"},\"image\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds - Sygnature","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/","og_locale":"fr_CA","og_type":"article","og_title":"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds - Sygnature","og_url":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/","og_site_name":"Sygnature","article_modified_time":"2026-01-30T12:15:13+00:00","og_image":[{"width":2560,"height":1707,"url":"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/sygnature-hit-to-lead-team-collaboration-scaled.webp","type":"image\/webp"}],"twitter_card":"summary_large_image","twitter_misc":{"Estimation du temps de lecture":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/","url":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/","name":"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds - Sygnature","isPartOf":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#website"},"datePublished":"2018-04-14T12:11:00+00:00","dateModified":"2026-01-30T12:15:13+00:00","breadcrumb":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/#breadcrumb"},"inLanguage":"fr-CA","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/diastereoselective-synthesis-of-highly-substituted-amino-and-pyrrolidino-tetrahydrofurans-as-lead-like-molecular-scaffolds\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.sygnaturediscovery.com\/fr\/page-daccueil\/"},{"@type":"ListItem","position":2,"name":"Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino-Tetrahydrofurans as Lead-Like Molecular Scaffolds"}]},{"@type":"WebSite","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#website","url":"https:\/\/www.sygnaturediscovery.com\/fr\/","name":"Sygnature Discovery","description":"","publisher":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#organization"},"alternateName":"Sygnature","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.sygnaturediscovery.com\/fr\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"fr-CA"},{"@type":"Organization","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#organization","name":"Sygnature Discovery","url":"https:\/\/www.sygnaturediscovery.com\/fr\/","logo":{"@type":"ImageObject","inLanguage":"fr-CA","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#\/schema\/logo\/image\/","url":"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/11\/Logo.svg","contentUrl":"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/11\/Logo.svg","width":1,"height":1,"caption":"Sygnature Discovery"},"image":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#\/schema\/logo\/image\/"}}]}},"_links":{"self":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/journal-paper\/13457","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/journal-paper"}],"about":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/types\/journal-paper"}],"version-history":[{"count":0,"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/journal-paper\/13457\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/media?parent=13457"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/category?post=13457"},{"taxonomy":"resource_tag","embeddable":true,"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/resource_tag?post=13457"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}