Beyond the traditional antibacterial uses, aminoglycosides have been explored for their unforeseen applications, including potential treatment for genetic neural disorders, diseases associated with mutations of gap junction proteins and fungal infection. Among these novel applications of aminoglycosides, chemical modification of naturally occurring aminoglycosides is often necessary. One of such modified aminoglycosides, TC007, has been identified as a potent lead in the treatment of spinal muscular atrophy (SMA). However, the synthesis of 3-aminoglucopyransyl donor, essential for the synthesis of this compound is challenging, it either involves metal-based reagents or requires more than ten synthesis steps with a very poor overall yield. Therefore, there is a need for improving the synthesis of 3-aminoglucopyransyl donor that is crucial for the preparation of TC007. Many naturally occurring or synthetic bioactive compounds contain 3-aminoglucopyranosyl moieties. An alternative approach is to utilize natural products containing 3-aminopyranose. Herein, the acid catalyzed hydrolysis of kanamycin is utilized to obtain 3- aminoglucopyranose. The synthesis of the donor by this alternative method reduce the synthesis steps resulting in an overall improved yield of TC007.

Revised synthesis of TC007: Potent lead for SMA treatment

2019 Fall National Meeting

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