Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

The Synthesis of Oxazole-containing Natural Products

Graham, Thomas H. (2006) The Synthesis of Oxazole-containing Natural Products. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (6MB) | Preview


The first section describes the synthesis of the C1' to C11' side chain of leucascandrolide A. The key step of the synthesis is a modified Robinson-Gabriel synthesis of the oxazole. The C1' to C11' side chain was constructed in 9 steps and 7% overall yield.The second section describes the synthesis of 2-alkynyl oxazoles and subsequent transformations into a variety of useful motifs. The conjugate addition of nucleophiles to 2-alkynyl oxazoles under basic conditions affords vinyl ethers, vinyl thioethers and enamines. The addition of ethanedithiol affords dithiolanes that can be transformed into ethyl thioesters and ketones. Nucleophilic additions of thiols to 2-alkynyl oxazolines affords oxazoline thioethers. Additions of halides under acidic conditions stereoselectively affords vinyl halides that can be further transformed by Sonogashira cross-coupling reactions.The third section describes the synthesis of (-)-disorazole C1 and analogs. The macrocycle was constructed with minimal protecting group manipulations, using mild esterification and Sonogashira cross-coupling reactions. The convergent synthesis of disorazole C1 allowed for the synthesis of additional analogs. These analogs include the C14-t-butyl and C17-18-cyclopropane derivatives. Results from preliminary biological evaluations of synthetic intermediates, analogs and derivatives are also discussed.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Graham, Thomas H.thgraham@pitt.eduTHGRAHAM
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWipf, Peterpwipf@pitt.eduPWIPF
Committee MemberLazo, John S.lazo@pitt.eduLAZO
Committee MemberKoide, Kazunorikoide@pitt.eduKOIDE
Committee MemberFloreancig, Paul E.florean@pitt.eduFLOREAN
Date: 1 June 2006
Date Type: Completion
Defense Date: 5 January 2006
Approval Date: 1 June 2006
Submission Date: 4 January 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: disorazol; macrodiolide; tubulin; anti-cancer; Sorangium cellulosum
Other ID:, etd-01042006-164032
Date Deposited: 10 Nov 2011 19:30
Last Modified: 15 Nov 2016 13:35


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item