Marshall W. Logue
Professor Emeritus, Chemistry
- PhD, Ohio State University
Dr. Logue's research interests are in the application of organic synthesis to carbohydrates, C-nucleosides, and nucleotide analogues.
A number of nucleoside antibiotics contain unusual carbohydrates. Synthetic routes to these types of antibiotics would be greatly simplified if regio- and stereoselective modifications of the common carbohydrates were available. To this end, we are investigating the reactions of the carbohydrate cyclic ortho esters with organosilicon reagents.
C-nucleosides are nucleosides that contain a carbon - carbon linkage, instead of the normal carbon - nitrogen linkage between the carbohydrate and the heterocyclic base. This carbon - carbon linkage makes the synthesis of C-nucleosides much more difficult than the synthesis of normal nucleosides. Although a number of routes have been developed for C-nucleoside synthesis, most are not very general in scope. Because alkynyl ketones are excellent substrates for elaboration to heterocyclic bases, we are interested in developing short and high-yield syntheses for glycosyl alkynyl ketones, which should serve as excellent precursors for C-nucleosides.
Many of the nucleoside antibiotics exhibit their activity only after conversion into their nucleotide form (mono- or triphosphate) once inside the cell. A number of nucleoside analogues which were expected to exhibit antibiotic activity were inactive because they are not substrates for the enzymes that phosphorylate nucleosides. Nucleotides themselves are not very useful as antibiotics because they are ionized at physiological pH and cannot be readily cross cell membranes. We wish to synthesize some nucleotide analogues, including acyclic C- nucleotide analogues, that have phosphate group masked as phosphate esters. These phosphate esters being covalent will be less polar and more able to cross cell membranes. However, the masking groups must be chosen such that they will be readily cleaved by cellular enzymes once inside the cell to free up the active nucleotide.
- Application of organic synthesis to carbohydrates, C-nucleosides, and nucleotide analogues
- Reactions of carbohydrate cyclic ortho esters with organosilicon reagents
- Developing short and high-yield syntheses for glycosyl alkynyl ketones
- Synthesis of nucleotide analogues, including acyclic C- nucleotide analogues, that have phosphate group masked as phosphate esters