An Efficient Gram-Scale Total Synthesis of Neoponkoranol as Potent α-Glucosidase Inhibitor

Author(s): Wang Zihao , Huang Yuhao , Liu Dan , Xu Jinyi , Tanabe Genzoh , Muraoka Osamu , Wu Xiaoming* , Xie Weijia* .

Journal Name: Current Organic Chemistry

Volume 22 , Issue 9 , 2018

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Abstract:

Background: Neoponkoranol is one of de-O-sulfonated sulfonium salts isolated from Genus Salacia showing potent inhibitory activities against α-glucosidases. In previously reported synthetic strategies, the two key coupling partners should be firstly constructed from different starting materials and the following coupling reaction is usually time-consuming. Thus, a more efficient and scalable synthetic protocol would be necessary for further SAR studies of this bioactive natural product.

Objective: Based on our previous synthetic studies on this series of natural products, the aim of the present study is to develop a novel total synthesis of neoponkoranol in a divergent and efficient way starting from inexpensive commercially available D-glucose. This is the first report of gram-scale synthesis of neoponkoranol.

Method and Results: Unlike all other reported strategies, the two coupling partners epoxide (14) and thiosugar (19) were firstly synthesized from an identical intermediate diol (12) which could be easily obtained in 3 steps from D-glucose. Notably, the construction of 14 and 19 could be achieved without any purification process. The subsequent acid mediated coupling reaction between resulted coupling partners was accomplished in only 4 hours while previous strategies usually took several days to complete the process. A gram-scale quantity of coupling reaction was then conducted under the same reacting condition and the desired sulfonium salt was isolated without any loss of the yield.

Conclusion: The newly developed scalable synthesis of neoponkoranol provided a good opportunity for further pharmaceutical studies on this bioactive natural product.

Keywords: Gram-scale total synthesis, Salacia, neoponkoranol, antidiabetic, α-glucosidase inhibitor, thiosugar.

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Article Details

VOLUME: 22
ISSUE: 9
Year: 2018
Page: [930 - 935]
Pages: 6
DOI: 10.2174/1385272821666170821150041
Price: $58

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