Login

Publications  •  Project Statistics

Glossary  •  Schools  •  Disciplines
People Search: 
   
Title/Abstract Search: 

Dissertation Information for Marike Herold

NAME:
- Marike Herold

DEGREE:
- Ph.D.

DISCIPLINE:
- Chemistry

SCHOOL:
- Emory University (USA) (2005)

ADVISORS:
- Dennis C. Liotta

COMMITTEE MEMBERS:
- Frank E. McDonald
- Debra L. Mohler

MPACT Status: Fully Complete

Title: Part I: Diastereoselective one-pot syntheses of azetines and beta-lactams starting from nitriles. Part II: Novel curcumin analogs as antitumor agents

Abstract: Part I of this dissertation describes the addition of chlorotitanium enolates of N -acylated thiazolidine-2-thiones to sulfinimines to form azetine derivatives as single diastereomers. This reaction shows remarkable preference for the formation of strained four membered over that of six membered rings. Azetine derivatives could also be formed in a highly diastereoselective and high yielding one-pot procedure starting from accessible nitriles. This methodology was found to be applicable for non-enolizable as well as enolizable nitriles. By using more thiaphilic than oxaphilic Lewis acids this reaction could be redirected and â-lactams were formed in high yields instead of azetines. A combination of Lewis acids, namely pentamethylcyclopentadienyl titanium trichloride and titanium chloroisopropoxides, results in diastereoselectivities up to 10 to 1. But interestingly, the absolute stereochemistries observed in the formation of lactams are opposite to those observed in the azetines. The power of this novel methodology was demonstrated by the efficient synthesis of the cholesterol absorption inhibitor SCH 48462. Part II examines the design and syntheses of novel curcumin analogs as inhibitors of tumor growth. The GI 50 values in breast cancer cell lines (MDA-231) ranged from 1 to 5 ìM and thus inhibit tumor cell growth with a higher potency than the commonly used chemotherapeutic drug, cisplatin. A biotin and two fluorescent labels were attached to a lead compound allowing to observe localization of the drug in the nucleus of the cancerous cell with light and confocal microscopy.

MPACT Scores for Marike Herold

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-03-22 16:00:50

Advisors and Advisees Graph