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. / Chemistry and Chemical Biology
| Identifer | oai:union.ndltd.org:harvard.edu/oai:dash.harvard.edu:1/11744417 |
| Date | 04 February 2015 |
| Creators | Milgram, Benjamin Charles |
| Contributors | Shair, Matthew David |
| Publisher | Harvard University |
| Source Sets | Harvard University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Rights | open |
Page generated in 0.0018 seconds