| Research Abstract |
An effective method for the preparation of 8-membered ring enone, an important synthetic intermediate of anti-tumor agent Taxol, in sufficient quantities was developed. First, optically active trialkoxyaldehyde was prepared by diastereoselective dihydroxylation of the olefm derived from D-pantolactone. Secondly, 8-chloro-7-oxoaldehydes were newly synthesized by the following reactions:namely, MgBr2-OEt2-mediated diastereoselective aldol reaction of the aldehyde with ketene(trimethylsilyl) acetal, and direct chloroethylation of an ester prepared from the aldol using 1, 1-dichloroethyllithium. Then, the chiral 8-chloro-7-oxoaldehydes were converted to the 8-membered ring enone by samarium(II) iodide-mediated aldol cyclization.
Furthermore, AB ring model system of 18-hydroxy Taxol was synthesized by cesium fluoride-mediated intramolecular Knoevenagel reaction of a bicyclic precursor possessing diketoester moiety derived from 8-membered ring ketone.
A polyoxy 8-membered ring compound containing a bis-aldol skeleton, a key synthetic intermediate of 19-hydroxy Taxol, was also prepared in high yield from α, β-epoxy ketoaldehyde by the samarium(II) iodide-mediated intramolecular cyclization.
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