Proposed herein is the development of new chemistry for the de novo synthesis of carbohydrates and the use of this new methodology for the synthesis of new bioactive molecules. These new bioactive structures may have activities against a range of diseases. This proposal is focus on anticancer and antibacterial compounds. The approach toward cancer is to use this new methodology to preform novel SAR studies on the carbohydrate portion of known natural products with anticancer activity. This approach will be conducted on the carbohydrate portions of digitoxin, SL0101 and Landomycin A. With regard to antibacterial agents this proposal is focused on addressing the problem of bacterial resistance. The major objectives of this proposal are to develop a concise methodology toward unnatural sugars, to develop a method for the assembly of unnatural sugars into unnatural oligosaccharides and to incorporate these unnatural sugars into carbohydrate based antibiotics, etc. Having unnatural sugar analogues of these antibiotics/antitumor agents would greatly aid in revealing which functional groups are important to these molecular interactions and in turn help prepared new more potent drugs.
This project from the department of chemistry at West Virginia University proposes to develop a new technology (glycosylation/cyclitolization) for the installation of natural and unnatural complex carbohydrates into existing natural product structural motifs. These new carbohydrate structures are based on naturally occurring structural motifs that nature use to impart biological activity into its existing natural products. Ultimately, we plan to uses these new compounds to development new pharmaceutical based therapies for the treatment of cancer and various infectious diseases. In addition, it is believed that this new approach will empower medicinal chemist to carry out new SAR type studies on the carbohydrate subunits of natural products.
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