Stereoselective synthesis and anticancer activity of broussonetine analogues

Synthesis and Glycosidase Inhibition of Broussonetine M and Its Analogues

“…According to our previous study on the synthesis and glycosidase inhibition of broussonetines [39,40], enantiomers of the above broussonetines would probably demonstrate a similar inhibitory profile by analogy with LAB ( ent -1 ) and l -DMDP ( ent -2 ), and as such [22,26,41,42], these compounds may have potential in the treatment of type II diabetes, cancers, and viral infections [43,44,45,46]. Hence, in this work, broussonetine M ( 3 ) was selected as the research objective; synthesis and glycosidase inhibition of the natural product and its analogues, including l -enantiomers and pyrrolidine core stereoisomers, were finished, aiming for a better understanding of structure–activity relationship (SAR) of this interesting class of pyrrolidine iminosugars.…”

“…Though the first synthesis of broussonetine M ( 3 ) was accomplished with d -serine as the starting material [47], we have shown that most broussonetines can be efficiently constructed via a general synthetic strategy employing sugar-derived cyclic nitrones [39,40]. The pyrrolidine core of this class of iminosugars can be derived from cyclic sugar nitrones [44,48,49,50] with the corresponding stereochemistry in the hydroxylated pyrrolidine ring, while the various side chains could be installed via cross-metathesis (CM) reactions [46,47,51,52]. This general strategy is capable of synthesizing a number of natural broussonetines, as well as a variety of broussonetine analogues for SAR study; it has been successful in the synthesis of broussonetine I ( 7 ), J 2 ( 10 ), and W ( 11 ) [39,40].…”