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Synthesis 2009(20): 3477-3487  
DOI: 10.1055/s-0029-1216954
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Vivien Henryona, Jean-Pierre Férézou*b
a Activation Chemical Process Research & Catalysis, 11, avenue Albert Einstein, 69100 Villeurbanne, France
Fax: +33(4)78931964;
b Laboratoire de Syntèse Organique, DCSO, UMR CNRS 7652, Ecole Polytechnique, 91128 Palaiseau cedex, France
Fax: +33(1)69335972; e-Mail: ferezou@dcso.polytechnique.fr;
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Publikationsverlauf

Received 10 June 2009
Publikationsdatum:
21. August 2009 (online)

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Abstract

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.

Key words

antibiotics - stereoselective synthesis - macrocycles - spiro compounds - cyclizations

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