Formal Convergent Synthesis of Ivermectin Aglycone - A Synthetic Approach to the C10-C25 Subunit of Avermectins 2b

A convergent, two-fragment synthesis of the C10-C25 northern moiety of avermectins has been developed. Along with our previous work in this area, the present contribution represents a formal synthesis of Ivermectin aglycone. Furthermore, according to a strategy leading to non gamma-pyranone adducts from the condensation reaction between acetylacetone dianion and convenient aldehydes, 23-hydroxylated C10-C25 northern building blocks required for the synthesis of the avermectins series 2b were prepared. Subsequent unexpected kinetically favored unnatural (21 S)-spiro isomers were obtained under mild cyclization conditions.