dc.creator | Hempel, Jonathan Edward | |
dc.date.accessioned | 2020-08-23T16:23:58Z | |
dc.date.available | 2014-12-21 | |
dc.date.issued | 2012-12-21 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-12212012-101204 | |
dc.identifier.uri | http://hdl.handle.net/1803/15328 | |
dc.description.abstract | The hibarimicin family of natural products was isolated in 1995 from the culture broth of the rare actinomycete Microbispora rosea subsp. hibaria TP-A0121. This complex polyketide type II family exhibits strong inhibition of src tyrosine kinase (IC50 = 580 nM to 2.32 µM), and hibarimicin B exhibited potent growth inhibition of the HL-60 leukemia cell line (IC50 = 58 nM) and in vitro cytotoxicity against B16-F10 and HCT-116 cells. Due to the inaccessibility of these biologically important compounds, we specifically sought out a synthetic route to access quantities of hibarimicin B and its biosynthetic precursors. Thus, chapter I details aromatic polyketides and related structural and synthetic considerations including the hibarimicins. Chapter II highlights application of the Diels-Alder reaction to total synthesis and previous synthetic efforts toward the hibarimicins. Chapter III discusses a two-directional strategy toward HMP-Y1 and hibarimicinone, and Chapters IV and V detail a biomimetic dimerization approach. | |
dc.format.mimetype | application/pdf | |
dc.subject | natural products | |
dc.subject | total synthesis | |
dc.subject | aromatic polyketides | |
dc.subject | Diels-Alder | |
dc.title | Studies Toward the Total Synthesis of HMP-Y1 and Hibarimicinone | |
dc.type | dissertation | |
dc.contributor.committeeMember | Professor Jeffrey N. Johnston | |
dc.contributor.committeeMember | Professor Brian O. Bachmann | |
dc.contributor.committeeMember | Professor Craig W. Lindsley | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Chemistry | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2014-12-21 | |
local.embargo.lift | 2014-12-21 | |
dc.contributor.committeeChair | Professor Gary A. Sulikowski | |