dc.contributor.advisor | Shair, Matthew David | |
dc.contributor.author | Milgram, Benjamin Charles | |
dc.date.accessioned | 2014-02-25T17:45:10Z | |
dash.embargo.terms | 2015-02-04 | en_US |
dash.embargo.terms | 2015-02-04 | |
dc.date.issued | 2014-02-25 | |
dc.date.submitted | 2013 | |
dc.identifier.citation | Milgram, Benjamin Charles. 2013. Progress Toward the Total Synthesis of Vinigrol and Hibarimicin B. Doctoral dissertation, Harvard University. | en_US |
dc.identifier.other | http://dissertations.umi.com/gsas.harvard:11220 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:11744417 | |
dc.description.abstract | Vinigrol is a structurally unique diterpenoid natural product featuring a tricyclo[4.4.4.0.4a,8a]tetradecene carbon skeleton containing eight contiguous stereocenters and a challenging oxygenation pattern. Vinigrol has been demonstrated to possess a wide array of biological activities including tumor necrosis factor (TNF) antagonism, antihypertensive activity, and platelet aggregation inhibitory activity. Our first-generation plan for the synthesis of vinigrol utilized a cascade reaction sequence involving: (1) diastereoselective alkylation of an α-alkenyl-β-ketoester, (2) retro-aldol-aldol equilibration (3) anion-accelerated oxy-Cope rearrangement, and (4) transannular Dieckmann condensation to afford the bicyclo[5.3.1]undecene ring system of vinigrol in a single operation. Discoveries concerning the limitations of this process are disclosed. Our second-generation approach to vinigrol employed a cis-decalin substrate in an alternative cascade reaction sequence, which was expected to deliver the complete tricyclo[4.4.4.0.4a,8a]tetradecene carbon skeleton of vinigrol in one step. An unexpected deviation from the envisioned reaction pathway instead afforded an alternative tricyclic enol silane. | en_US |
dc.description.sponsorship | Chemistry and Chemical Biology | en_US |
dc.language.iso | en_US | en_US |
dash.license | LAA | |
dc.subject | Organic chemistry | en_US |
dc.subject | Angelmicin | en_US |
dc.subject | Hibarimicin | en_US |
dc.subject | Natural Product | en_US |
dc.subject | Total Synthesis | en_US |
dc.subject | Vinigrol | en_US |
dc.title | Progress Toward the Total Synthesis of Vinigrol and Hibarimicin B | en_US |
dc.type | Thesis or Dissertation | en_US |
dash.depositing.author | Milgram, Benjamin Charles | |
dc.date.available | 2015-02-04T08:30:40Z | |
thesis.degree.date | 2013 | en_US |
thesis.degree.discipline | Chemistry and Chemical Biology | en_US |
thesis.degree.grantor | Harvard University | en_US |
thesis.degree.level | doctoral | en_US |
thesis.degree.name | Ph.D. | en_US |
dc.contributor.committeeMember | Myers, Andrew | en_US |
dc.contributor.committeeMember | Kishi, Yoshito | en_US |
dash.contributor.affiliated | Milgram, Benjamin Charles | |