Stereo- and substituent-enabled divergent synthesis of 5, 6-spiroketal analogs of avermectin containing a triazole function. Issue 32 (9th August 2017)

• Record Type: Journal Article
• Authors: Yamada, Takeshi; Horimatsu, Yuki; Hirose, Tomoyasu; Sugawara, Akihiro; Ōmura, Satoshi; Sunazuka, Toshiaki
• Is Part Of: Tetrahedron letters. Volume 58:Issue 32(2017)
• Page Start: 3119
• Page End: 3124
• Publication Date: 2017-08-09
• Subjects: Ivermectin -- Spiroketal -- Click chemistry -- Diversity -- Anthelmintic drug; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2017.06.072
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Divergent synthesis and nematocidal activity of avermectin analogs. Stereodivergent 5, 6-spirocyclization. One-pot triazole formation between three TMS-alkynes and organic azides. Alkyne analogs showed comparable nematocidal activity to that of ivermectin. 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.