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.