eprintid: 9885
rev_number: 5
userid: 6
dir: disk0/00/00/98/85
datestamp: 2011-11-10 20:07:00
lastmod: 2016-11-15 13:52:30
status_changed: 2011-11-10 20:07:00
type: thesis_degree
metadata_visibility: show
contact_email: Nachemura.org@gmail.com
item_issues_count: 0
eprint_status: archive
creators_name: Nakamura, Akira
creators_email: akn8@pitt.edu, Nachemura.org@gmail.com
creators_id: AKN8
title: Enantioselective Synthesis of Mefloquine Analogs and Their Derivatives
ispublished: unpub
divisions: sch_as_chemistry
full_text_status: public
keywords: Mefloqune; Palladium cross-coupling
abstract: Mefloquine is a clinically useful anti-malarial compound active against strains of the Plasmodium parasite. The behavioral effects of each of the enantiomers of mefloquine were assessed. The (+)-(11R,12S)-enantiomer showed higher activity against Plasmodium falciparum. Progress has been made toward the enantioselective synthesis of the (+)-(11R,12S)-8-chloromefloquine analog. An enantiometically pure product was obtained by using hydrozirconation followed by a zinc-palladium catalyzed Negishi cross-coupling reaction and a Sharpless dihydroxylation as key steps.A series of mefloquine analogs have been developed to facilitate future structure-activity relationships and the development of new antimalaria agents. A recent study suggested an increase in the potency with electron-withdrawing groups at both the 2- and 8-positions of the quinoline ring. According to this concept, six new 8-position derivatives were synthesized via a palladium mediated coupling reaction.
date: 2010-01-26
date_type: completed
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_chair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Wipf, Peter
etdcommittee_name: Curran, Dennis P
etdcommittee_name: Chapman, Toby
etdcommittee_email: pwipf@pitt.edu
etdcommittee_email: curran@pitt.edu
etdcommittee_email: tchapman@imap.pitt.edu
etdcommittee_id: PWIPF
etdcommittee_id: CURRAN
etdcommittee_id: TCHAPMAN
etd_defense_date: 2009-10-30
etd_approval_date: 2010-01-26
etd_submission_date: 2009-11-30
etd_access_restriction: 5_year
etd_patent_pending: FALSE
assigned_doi: doi:10.5195/pitt.etd.2011.9885
thesis_type: thesis
degree: MS
committee: Peter Wipf (pwipf@pitt.edu) - Committee Chair
committee: Dennis P. Curran (curran@pitt.edu) - Committee Member
committee: Toby Chapman (tchapman@imap.pitt.edu) - Committee Member
etdurn: etd-11302009-133233
other_id: http://etd.library.pitt.edu/ETD/available/etd-11302009-133233/
other_id: etd-11302009-133233
citation:   Nakamura, Akira  (2010) Enantioselective Synthesis of Mefloquine Analogs and Their Derivatives.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/9885/1/Nakamura_etd2009.pdf