Title:An Efficient Gram-Scale Total Synthesis of Neoponkoranol as Potent α-Glucosidase Inhibitor
VOLUME: 22 ISSUE: 9
Author(s):Wang Zihao, Huang Yuhao, Liu Dan, Xu Jinyi, Tanabe Genzoh, Muraoka Osamu, Wu Xiaoming* and Xie Weijia*
Affiliation:Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009
Keywords:Gram-scale total synthesis, Salacia, neoponkoranol, antidiabetic, α-glucosidase inhibitor, thiosugar.
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.
