An unusual twist in the synthesis and hydrolysis of the 23,24-epoxide of 22,23-dihydroavermectin B1a

✍ Scribed by Thomas L. Shih; Helmut Mrozik; Mark A. Holmes; Bryon H. Arison; George A. Doss; Frank Waksmunski; Michael H. Fisher

• Publisher: Elsevier Science
• Year: 1992
• Tongue: French
• Weight: 284 KB
• Volume: 33
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)91712-x

✦ Synopsis

Treatment of 4",S-di-G-tert-butyldimethylsilyl(or phenoxyacetyl)-7-0-trimethylsilyl-avenue&n B2a (la,b) with diethylaminosulfur trifluoride (DAST) at 20AC in dichloromethane resulted in net elimination of water to yield 65% of the 23,24-olefin (Za,b), 510% 23-fluoroavermectin derivative (3a,b), and 20-25% of two rearranged products (4a,b:5a,b in a 2:l ratio). The trisubstituted 23,24-olefin (2a,b) was selectively epoxidized with m-chloroperbenzoic acid to give a mixture of alpha (6a,b major) and beta (7a,b minor) 23,24-epoxides in 64% yield. The acid catalyzed hydrolysis of epoxide 6a,b unexpectedly afforded hemiketal 9a,b as the major prduct (60%) and the usual 23,24-diol lOa,b as the minor product (6%). Subsequent Ley perruthenate oxidation of 9b produced lactone 13b in 15% yield. Lead tetracetate oxidation of 10a produced the desired cleavage product 14a in 40-50% yield.