Stereo- and substituent-enabled divergent synthesis of 5,6-spiroketal analogs of avermectin containing a triazole function

Abstract Stereo-divergent construction of a 5,6-spiroketal moiety, together with an efficient strategy to access various avermectin analogs containing a triazole group, has been accomplished. In the spirocyclization event, a C21 R spiroketal product was selectively obtained using Zn(OTf) 2 as a Lewis acid. Conversely, use of Sc(OTf) 3 afforded a C21S spiroketal compound as the major product. One pot triazole formation between three TMS-alkyne substrates and organic azides effectively provided the corresponding anti-triazole products. This strategy generates stereochemical and substituent diversity among avermectin analogs. Some of the 5,6-spiroketal analogs showed anti-nematodal activity comparable to ivermectin.