dc.creator | Dobish, Mark Christopher | |
dc.date.accessioned | 2020-08-23T16:13:06Z | |
dc.date.available | 2015-01-18 | |
dc.date.issued | 2013-01-18 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-12052012-115555 | |
dc.identifier.uri | http://hdl.handle.net/1803/15152 | |
dc.description.abstract | Herein we demonstrate the development and application of chiral bis(amidines) as organocatalysts in novel enantioselective transformations. A chiral, Brønsted base-catalyzed asymmetric alkylation of nitroalkanes is described for the first time using bis(amidine) catalysis, delivering products with synthetically useful values of enantiomeric excess. Additionally, the first enantioselective synthesis of VNI, a potent CYP51 inhibitor, is divulged and highlighted by an enantioselective bromonitromethane aza-Henry addition to afford the desired intermediate with high enantioselectivity. Ultimately, gram quantities of VNI were synthesized to establish its efficacy in a murine model of chronic Chagas, a neglected tropical disease. Finally, the highly enantioselective iodolactonization of 1,1- and 1,2-disubstituted olefinic acids using chiral proton catalysis is reported, where steric and electronic modification of an achiral counterion offers a handle to control enantioselection. | |
dc.format.mimetype | application/pdf | |
dc.subject | bisamidine catalysis | |
dc.subject | small molecule therapeutic | |
dc.subject | organocatalysis | |
dc.subject | chiral proton catalysis | |
dc.subject | Chagas disease | |
dc.subject | enantioselective iodolactonizations | |
dc.title | Chiral bisamidine catalysis: enantioselective alkylations and halolactonizations with applications to small molecule therapeutics | |
dc.type | dissertation | |
dc.contributor.committeeMember | Michael R. Waterman | |
dc.contributor.committeeMember | Ned A. Porter | |
dc.contributor.committeeMember | Timothy P. Hanusa | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Chemistry | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-01-18 | |
local.embargo.lift | 2015-01-18 | |
dc.contributor.committeeChair | Jeffrey N. Johnston | |