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 γ-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 (21S)-spiro
isomers were obtained under mild cyclization conditions.
antibiotics - stereoselective synthesis - macrocycles - spiro compounds - cyclizations