A streamlined synthetic pathway to target the core of plakortether B through a zinc-mediated homologation-aldol reaction has been developed. This chemistry was performed on a chiral beta-keto amide, which was synthesized in a few steps. In a one-pot reaction the beta-keto amide could be converted into a furanyl-ketal with high stereocontrol at two chiral centers. The homologation-aldol reaction was followed by a cyclization-allylation to obtain the plakortether backbone.
During the synthesis of plakortether B, a serendipitous byproduct was identified as a [3.1.0] bicyclic lactone. The lactone was seen as a precursor to a peptidomimetic that would contain an embedded hydroxycyclopropyl moiety. The formation of the bicyclic lactones was proposed to involve a cascade of homologation-cyclopropanation-rearrangement-lactonization reactions. Amino acid-derived beta-keto imides were synthesized in order to enhance the stereocontrol of the tandem lactonization reaction. The use of amino acid derived beta-keto imides was beneficial in two ways; first it incorporates an amino acid directly into the peptide isotere and influences the diastereocontrol.
The homologation-cyclization-rearrangement-lactonization reaction of beta-keto imides has proven to be successful for the formation of [3.1.0] bicyclic lactones as precursors to peptide isosteres.
","abstract_html":"<p>A streamlined synthetic pathway to target the core of plakortether B through a zinc-mediated homologation-aldol reaction has been developed. This chemistry was performed on a chiral beta-keto amide, which was synthesized in a few steps. In a one-pot reaction the beta-keto amide could be converted into a furanyl-ketal with high stereocontrol at two chiral centers. The homologation-aldol reaction was followed by a cyclization-allylation to obtain the plakortether backbone.</p><p>During the synthesis of plakortether B, a serendipitous byproduct was identified as a [3.1.0] bicyclic lactone. The lactone was seen as a precursor to a peptidomimetic that would contain an embedded hydroxycyclopropyl moiety. The formation of the bicyclic lactones was proposed to involve a cascade of homologation-cyclopropanation-rearrangement-lactonization reactions. Amino acid-derived beta-keto imides were synthesized in order to enhance the stereocontrol of the tandem lactonization reaction. The use of amino acid derived beta-keto imides was beneficial in two ways; first it incorporates an amino acid directly into the peptide isotere and influences the diastereocontrol.</p><p>The homologation-cyclization-rearrangement-lactonization reaction of beta-keto imides has proven to be successful for the formation of [3.1.0] bicyclic lactones as precursors to peptide isosteres.</p>","abstract_has_math":false,"creators":["Taschner, Ian Scott"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Charles K Zercher"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-01T08:00:00Z","date_published":"2011-01-01T08:00:00Z","updated_at":"2026-07-24T05:22:31Z","subjects":["Chemistry","Organic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholars.unh.edu/dissertation/576","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Charles K Zercher"]},{"key":"dc:creator","label":"Author","values":["Taschner, Ian Scott"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry","Organic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholars.unh.edu/dissertation/576"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A streamlined synthetic pathway to target the core of plakortether B through a zinc-mediated homologation-aldol reaction has been developed. This chemistry was performed on a chiral beta-keto amide, which was synthesized in a few steps. In a one-pot reaction the beta-keto amide could be converted into a furanyl-ketal with high stereocontrol at two chiral centers. The homologation-aldol reaction was followed by a cyclization-allylation to obtain the plakortether backbone.
During the synthesis of plakortether B, a serendipitous byproduct was identified as a [3.1.0] bicyclic lactone. The lactone was seen as a precursor to a peptidomimetic that would contain an embedded hydroxycyclopropyl moiety. The formation of the bicyclic lactones was proposed to involve a cascade of homologation-cyclopropanation-rearrangement-lactonization reactions. Amino acid-derived beta-keto imides were synthesized in order to enhance the stereocontrol of the tandem lactonization reaction. The use of amino acid derived beta-keto imides was beneficial in two ways; first it incorporates an amino acid directly into the peptide isotere and influences the diastereocontrol.
The homologation-cyclization-rearrangement-lactonization reaction of beta-keto imides has proven to be successful for the formation of [3.1.0] bicyclic lactones as precursors to peptide isosteres.
"]},{"key":"dc:title","label":"Title","values":["I Progress towards the synthesis of plakortether B through a zinc-mediated homologation II Synthesis of novel hydroxy-cyclopropyl peptides isosteres"]}]}],"canonical_facts":{"dc:contributor":["Charles K Zercher"],"dc:creator":["Taschner, Ian Scott"],"dc:description.abstract":["A streamlined synthetic pathway to target the core of plakortether B through a zinc-mediated homologation-aldol reaction has been developed. This chemistry was performed on a chiral beta-keto amide, which was synthesized in a few steps. In a one-pot reaction the beta-keto amide could be converted into a furanyl-ketal with high stereocontrol at two chiral centers. The homologation-aldol reaction was followed by a cyclization-allylation to obtain the plakortether backbone.
During the synthesis of plakortether B, a serendipitous byproduct was identified as a [3.1.0] bicyclic lactone. The lactone was seen as a precursor to a peptidomimetic that would contain an embedded hydroxycyclopropyl moiety. The formation of the bicyclic lactones was proposed to involve a cascade of homologation-cyclopropanation-rearrangement-lactonization reactions. Amino acid-derived beta-keto imides were synthesized in order to enhance the stereocontrol of the tandem lactonization reaction. The use of amino acid derived beta-keto imides was beneficial in two ways; first it incorporates an amino acid directly into the peptide isotere and influences the diastereocontrol.
The homologation-cyclization-rearrangement-lactonization reaction of beta-keto imides has proven to be successful for the formation of [3.1.0] bicyclic lactones as precursors to peptide isosteres.
"],"dc:identifier":["https://scholars.unh.edu/dissertation/576"],"dc:subject":["Chemistry","Organic"],"dc:title":["I Progress towards the synthesis of plakortether B through a zinc-mediated homologation II Synthesis of novel hydroxy-cyclopropyl peptides isosteres"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:22:31Z"}