Hydroxy-directed diastereoselective installation of a methyl group on indalone models and spiroketal potential precursors for the bafilomycin A(1) C15-C25 subunit.
Current efforts devoted to the synthesis of Bafilomycin A(1) led us to investigate a synthetic route through a spiroketal intermediate for the construction of the C15-C25 subunit. Preliminary studies for the diastereoselective installation of the methyl-16 cis with respect to the vicinal OH-15 group through radical opening of either siloxafuran intermediate 7 or cyclopropyl compounds 9 and 13 have been carried out using model compounds derived from commercial Indalone 6. In each case the expected "cis" diastereoisomer was obtained in good to excellent yield. Application of these results to Bafilomycin A(1) synthon led to the opposite "trans" stereoselectivity when alpha-carboxy- or alpha-keto-substituted spiroketals 4 or 19 were used. However, the expected potential intermediate has been obtained from the alpha-hydroxymethyl cyclopropanated synthon 21. A Barton-Motherwell xanthate radical deoxygenation-cylopropane opening methodology, followed by a hydroboration-oxidation of the exovinylic intermediate, delivered the expected product 22cis in high yield and excellent stereoselectivity.
Poupon
Jean-Christophe
JC
Laboratoire de Synthèse Organique associé au CNRS, UMR 7652, Ecole Polytechnique, DCSO, 91128 Palaiseau, France.
Lopez
Roman
R
Prunet
Joëlle
J
Férézou
Jean-Pierre
JP