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.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.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.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 University of Texas at Austinen of Philosophyen

Access full-text files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
2 MB
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
1.65 KB
Plain Text