The scientific value of the proposed research lies in the contributions to basic and applied synthetic carbohydrate chemistry that will result upon successful completion of the project. Glycosyl thioimidates are potentially valuable synthetic building blocks due to their unusual reactivity profile, stereoselectivity, ease of preparation, and stability. Exploration of these glycosyl donors will provide better understanding of the mechanism of activation and the departure of the leaving group. Due to their remarkable stereoselectivity and reactivity vs. stability, the thioimidates have a potential to find an important niche in the arsenal of modern glycosylation techniques. Upon development of the thioimidate method, the focus will shift to the investigation of arming and disarming effects in carbohydrate chemistry and invention of the inverse armed-disarmed approach. Investigation of these important aspects will only be possible due to the unusual reactivity and activation profile of glycosyl thioimidates. Developing these techniques will serve to demonstrate the synthetic potential of thioimidate method while also delivering synthetic analogs of natural glycoconjugates that mediate important biological processes in carcinomas. Other important aspects of this work relate to the professional training in preparative organic and carbohydrate chemistry, as well as modern physico-chemical methods for analysis of complex organic molecules that the undergraduate and graduate research participants will receive. 2 summer research undergraduate fellowships and 2 graduate student positions are budgeted in this proposal; the PI's group has traditionally supported the involvement of women, children, and minorities. The multidisciplinary nature of the proposed research will allow students to expand their scientific base in both an intellectual and a practical sense. During their laboratory experience they will learn important tools that allow chemists to synthesize, modify, and analyze organic molecules while developing new ('their own') synthetic methodologies and participating in elaboration of state-of-the-art, multi-step syntheses. Student researchers will also become fully integrated into the scientific community through participation in the preparation of peer-reviewed manuscripts and through attendance at professional meetings. In this manner, students will develop better communication skills, while also being exposed to scientific discourse outside their focused area of research. ? ? ?
| Hasty, Scott J; Bandara, Mithila D; Rath, Nigam P et al. (2017) S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active-Latent, Armed-Disarmed, Selective, and Orthogonal Activations. J Org Chem 82:1904-1911 |
| Ranade, Sneha C; Demchenko, Alexei V (2015) Glycosyl alkoxythioimidates as building blocks for glycosylation: a reactivity study. Carbohydr Res 403:115-22 |
| Nigudkar, Swati S; Stine, Keith J; Demchenko, Alexei V (2014) Regenerative glycosylation under nucleophilic catalysis. J Am Chem Soc 136:921-3 |
| Gyore, Jacob; Parameswar, Archana R; Hebbard, Carleigh F F et al. (2014) 2-Acylamido analogues of N-acetylglucosamine prime formation of chitin oligosaccharides by yeast chitin synthase 2. J Biol Chem 289:12835-41 |
| Nigudkar, Swati S; Parameswar, Archana R; Pornsuriyasak, Papapida et al. (2013) O-Benzoxazolyl imidates as versatile glycosyl donors for chemical glycosylation. Org Biomol Chem 11:4068-76 |
| Avegno, Elizabeth Alverson-Banks; Hasty, Scott J; Parameswar, Archana R et al. (2013) Reactive thioglucoside substrates for ?-glucosidase. Arch Biochem Biophys 537:1-4 |
| Heuckendorff, Mads; Premathilake, Hemali D; Pornsuriyasak, Papapida et al. (2013) Superarming of glycosyl donors by combined neighboring and conformational effects. Org Lett 15:4904-7 |
| Ganesh, N Vijaya; Fujikawa, Kohki; Tan, Yih Horng et al. (2012) HPLC-assisted automated oligosaccharide synthesis. Org Lett 14:3036-9 |
| Hasty, S J; Demchenko, A V (2012) Glycosyl Thioimidates as Versatile Building Blocks for Organic Synthesis. Chem Heterocycl Compd (N Y) 48: |
| Tsytsarev, Vassiliy; Maslov, Konstantin I; Yao, Junjie et al. (2012) In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog. J Neurosci Methods 203:136-40 |
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