Synthesis and kinetic evaluation of substrate-based phospholipid analogues and studies towards the synthesis of 5-hydroxyaloin A

dc.contributor.advisorMartin, Stephen F.en
dc.creatorLi, Hui, 1975-en
dc.date.accessioned2008-08-28T22:08:40Zen
dc.date.available2008-08-28T22:08:40Zen
dc.date.issued2005en
dc.description.abstractIn the studies to establish structure-reactivity relationships in the hydrolytic reaction of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidyl L-serine (PS) catalyzed by the phospholipase C from Bacillus cereus (PC-PLCBc), a number of water-soluble, non-hydrolyzable substrate based inhibitors of PLCBc were prepared. These include ω-hydroxy phosphorodithioates and phosphonates of choline, ethanolamine and L-serine. Kinetic assays reveal that all the ω-hydroxy phosphorodithioates are good inhibitors with good aqueous solubilities. However, ethanolamine and L-serine derivatives of phosphonates fail to inhibit PLCBc at their maximum solubilities. The three-dimensional structures of phosphonate-PS with E4G, E4Q and wild type PC-PLCBc revealed that these mutants bind the PS analogue in a very different manner than wild-type does a PC analogue. The structural difference shed new views on our understanding of the mechanistic and kinetic aspects of PLCBc catalyzed hydrolytic reactions. In the application of our glycosyl furan/benzyne cycloaddition methodology towards natural product synthesis, a two-stage benzyne/furan cycloaddition strategy was used to assemble the anthrone core of Group I C-aryl glycoside 5-hydroxyaloin A. Proof of concept was established in the generation of benzyne from a chloronaphthol precursor 4.142 and subsequent cycloaddition with furan afford the cycloadduct 4.143. However, the cycloadducts of 4.142 and alkoxy/silyloxy furans were unstable, and attempts to convert them into 5-hydroxyaloin A were unsuccessful. During the course of the investigation, cycloadditions using glycal-substituted furans were investigated and a one-step novel approach to the C-aryl glycal was established starting from 2-deoxy sugar lactone.
dc.description.departmentChemistry and Biochemistryen
dc.description.departmentChemistryen
dc.format.mediumelectronicen
dc.identifierb59937087en
dc.identifier.oclc61409213en
dc.identifier.proqst3175268en
dc.identifier.urihttp://hdl.handle.net/2152/1612en
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshPhospholipids--Synthesisen
dc.subject.lcshOrganic compounds--Synthesisen
dc.titleSynthesis and kinetic evaluation of substrate-based phospholipid analogues and studies towards the synthesis of 5-hydroxyaloin Aen
dc.type.genreThesisen
thesis.degree.departmentChemistryen
thesis.degree.disciplineChemistryen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

Access full-text files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
lih79332.pdf
Size:
2 MB
Format:
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.65 KB
Format:
Plain Text
Description: