Asymmetric synthesis of polycyclic polyketides via the double Diels-Alder addition of 2,2 '-ethylidenebis[3,5-dimethylfuran]
The Diels-Alder adduct 3 of 2,2'-ethylidenebis(3,5-dimethylfuran) to diethyl (E,E)-4-oxohepta-2,5-diene-1,7-dioate was converted into meso-(1R,2R,4R,4aR,5S,7S,8S,8aS,9aS,10aS)- 1,8-bis(acetoxymethyl)- 1,3,4,5,6,7,8,8a,9,9a-decahydro-2,4,5,7,10 -pentamethyl-3,6,9-trioxo-2H,10H-2,4a:7,10a-diepoxy-anthracene (9). Enantioselective monoreduction of 9 with BH3. Me2S and a catalytic amount of methyloxazaborolidine derived from L-diphenylprolinol gave (1S,2S,4S,4aS,5S,6R,7R,8R,8aS,9aR,10R,10aS)-1,8-bis(acetoxymethyl-1,3,4, 5,6,7,8,8a,9,9a-decahydro-6- methyl-3,9-dioxo-2N,10H-2,4a:7,10a-diepoxyanthracene with 90% ee. Its absolute configuration was established by single crystal X-ray diffraction studies of the camphanate (-)-13 (1S,2S,4S,4aS,5S,6S,7R,8R,8aS,9aR,10R,10aS)- 8-acetoxymethyl-1-[(2'S,5'R)-camphanoyloxymethyl]-1,3,4,5,6,8,8a,9,9a-de cahydro-6-(methoxymethyl)-2,4,5,7,10-penta 2H,10H-2,4a:7,10a-diepoxyanthracene). Basic treatment of (-)-10 led to regioselective ethereal ring opening of the 7-oxabicyclo[2.2.1] heptan-2-one moiety at C-1,2,3,4,4a,9a with formation of (1R,2R,3R,4S,4aR,5S,7S,8S,9aS,10S)-1,8-diacetoxymethyl-1,3,4,5,6,7,8,9,9 a,10-decahydro-3,7-dihydroxy-2,4,5,7,10-pentamethyl methyl-6,9-dioxo-2H-2,4a-epoxyanthracen. Thus, desymmetrization of 9 via enantioselective triketone reduction allows the preparation of polycyclic polyketides with high stereochemical complexity and with high stereo- and enantioselectivity.
Univ Lausanne, BCH, Chim Sect, CH-1015 Lausanne, Switzerland. Univ Lausanne, BSP, Inst Cristallog, CH-1015 Lausanne, Switzerland.
Record created on 2005-11-09, modified on 2016-08-08