Absfracfi Avemectin B la A44,4a ,2, has been obtained from avenneztin B la. 1, and its bioactivity evaluated. The key step of the transfommtion is the reduction of an intemxdiate allylic radical with aBu@nH. The avermectins are disaccharide derivatives of a structurally similar group of pentacyclic 16membered lactones with unprecedented insecticidal and antiparasitic activities.1 Avermectin Bla 1 is the most important member, owing to its high potency against a broad spectrum of endo-and ecto~msites of farm animals and a variety of agricultural pests.2 Chemical modifications in all of the different regions of these molecules3 have been undertaken in the hope of improving their biological profile. The hexahydrobenzofuran unit, I, is of primary interest because it is one of the most delicate regions of the molecule. Owing to the presence of the A 3.4 double bond, C-2 epimerization to give II occurs readily, and under basic conditions the A314 double bond migrates into conjugation to give III.4 Interestingly II and III do not retain the biological activity of I, and hence our laboratory has devoted special attention to the development of strategies to avoid conjugation and epimerization of avermectin derivatives. 56 The lack of activities of II and III indicates the importance of the C-2 configuration, and it seemed to us that relocation of the C-3 double bond in 1 into an exccyclic position, as in 2, would (a) eliminate the deconjugation problem and (b) reduce the tendency for C-2 epimerization, and provided that no major conformational change would be involved,7 improved biological properties might result. In this communication we report on this transformation, 1 into 2, as well as on the bioactivity of 2.