Many bioactive natural products contain a spiroketal moiety in their complex structure. Recently, simplified spiroketals with antitumoral activity were described. Incorporation of a nitrogen atom can enhance the bioactivity, so we focused on the original class of spiroaminoketals. We have developed an enantioselective synthesis of spiroheterocycles allowing to vary the ring-size and the heteroatoms nature. Our strategy lies on an iterative one-pot alkylation keystep of acetone dimethylhydrazone with polyfunctionalised iodo synthons, followed by a deprotection-spirocyclisation process. Its efficiency has been illustrated by the synthesis of 1,7-dioxaspiro[5.5]undecane, 1,7-dioxaspiro [5.5]undecan-3-ol, 1,6-dioxaspiro[4.5]decanes and 7-aza-1-oxaspiro[5.5]undecane. We have also explored 6-aza-1-oxaspiro[4.5]decane and 7-aza-1-oxaspiro[5.4]decane series. The structural and conformational analysis (NMR and molecular modeling) and the first biological results on various cancer cells are given. Key
