Enantioselective synthesis of the C1-C11 fragment of bafilomycin A1 using non-Wittig and desymmetrization strategies.
The synthesis of the C1-C11 fragment 33 of bafilomycin A(1) was achieved. Intermediate ketone 16 was prepared in six steps from 4-oxopimelate 13. Desymmetrization of this ketone using Koga's chiral base followed by TMSCl quench furnished silyl enol ether 17 with excellent enantioselectivity. Further elaboration led to C5-C11 aldehyde 24, which was coupled with sulfone 3 to give lactone 25 in very good yield. The subsequent reductive elimination created the E-trisubstituted C4-C5 olefin with a 13:1 selectivity. The E C2-C3 double bond was then installed by methanol elimination, and compound 33 was obtained after a few functional group manipulations and a Negishi methyl zirconation.
Poupon
Jean-Christophe
JC
Laboratoire de Synthèse Organique associé au CNRS, UMR 7652, Ecole Polytechnique, DCSO, 91128 Palaiseau, France.
Demont
Emmanuel
E
Prunet
Joëlle
J
Férézou
Jean-Pierre
JP
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007659:Ketones / Q000737:chemistry*; D018942:Macrolides / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013305:Streptomyces griseus / Q000737:chemistry
D007659:Ketones; D018942:Macrolides; C057620:bafilomycin A