Date of Completion
Septanose, Glycosylations, Koenigs-Knorr, Ferrier, 1, 4-Anhydroseptanoses, Protein-Carbohydrate interactions
Dr. Mark W. Peczuh
Dr. Amy R. Howell
Dr. Nicholas E. Leadbeater
Field of Study
Doctor of Philosophy
Protein–carbohydrate interactions play a key role in many biological processes. For lectins, interactions result in the association of two biomolecules, whereas for glycosidases, association ultimately leads to catalysis in chemical reactions. We previously investigated protein–septanose interactions using the model lectin Concanavalin A. Here we report on a route to synthesize indoxyl and p-nitrophenyl septanosides via the corresponding septanosyl halides using a phase-transfer glycosylation methodology. The key intermediates for the synthesis of septanose glycoconjugates via septanosyl halides are per-O-acetyl septanoses which were prepared from benzyl protected pyranose lactols via a five-step reaction sequence.
During the synthetic investigation we observed differential rates of glycosyl halide formation of the per-O-acetyl septanoses based on the stereochemistry at C1 and C2 of the per-O-acetates. Also, we observed unexpected stereoselectivities in glycoside bond formation (α/β) that was dependent on a number of factors including the nature of the reaction method, electrophilic sugar species, and the incoming nucleophile. The results provided new parameters to consider when approaching septanose glycosylations. Importantly, the syntheses of indoxyl and p-nitrophenyl septanosides will enable the products to be used to interrogate septanose-glycosidase binding and hydrolysis.
While synthesizing carbohydrate based oxepines via a reductive elimination method; activation of the intermediate species such as di-O-acetyl septanoses via Bromination or Iodination afforded the unexpected 1,4-anhydroseptanoses. The regioselectivity of the cyclization was conﬁrmed by NMR spectroscopy and an X-ray structure of a glucose-derived 1,4-anhydroseptanose. The transformation is relatively general and was applied to septanoses derived from glucose, mannose, xylose, and galactose. To prove the importance of newly discovered species in glycosylation reactions, selective opening of the 1,4-anhydro species to obtain septanose glycoconjugates in preference to furanoses is also demonstrated.
In a separate study, direct glycosylation using carbohydrate based oxepines via Ferrier glycosylation was tested. Synthesis of glucose derived carbohydrate based oxepines as a starting material from per-O-acetyl septanose intermediates via classical Fisher-Zack reaction method was achieved. Currently, the oxepines are being tested with a variety of Lewis acid catalyst for optimization of yield and selectivity in glycosylations, intended for the direct synthesis of septanose glycoconjugates with desired aglycones.
Pote, Aditya, "Development Of New Strategies For The Synthesis Of Septanose Glycosides And Evaluation Of Their Potential Biological Applications" (2018). Doctoral Dissertations. 1973.
Available for download on Thursday, October 05, 2028