Application of Mn(III)-catalysed olefin hydration reaction to the selective functionalisation of avermectin B1

The Mn(dpm)3-catalysed olefin hydration reaction of α,β-unsaturated esters and ketones discovered by Mukaiyama in 1990 and further developed by Magnus in 2000 was applied to the challenging environment of avermectin B1. Different avermectin substrates such as 4″,7-OTMS-5-oxo-avermectin B1 3, avermectin B1 1 and Δ2,3-avermectin B1 6 were thus treated with Mn(dpm)3, PhSiH3 in isopropanol under oxygen atmosphere to afford several novel analogues, including 3,4-dihydro-3-hydroxy-avermectin B1 8 with high level of regio- and stereoselectivity, 2-hydroxy-3,4-dihydro-avermectin B1 7, the first example of a 2-substituted avermectin and the novel 22,23-dihydro-22-hydroxy-avermectin B1 9a and 9b, epimeric at C(22). Biological activity of these new avermectin derivatives is also reported.