Toward a total synthesis of amphidinolide X and Y. The tetrahydrofuran-containing fragment C12-C21.
The key THF derivative (9a) for an enantioselective synthesis of amphidinolide X/Y was obtained from 1a via a selenoetherification reaction. In fact, among the cyclization methods investigated, the highest yield and stereocontrol were achieved at -78 degrees C with PhSeCl/EtiPr2N from diols 1a (anti-Z) and 1b (anti-E) and with PhSeCl/ZnBr2 from diols 1c (syn-Z) and 1d (syn-E). Also, surprisingly, use of protecting groups (on the allylic OH) was detrimental in the cases studied. The diverse THF-tetrasubstituted stereoisomers will provide a series of amphidinolide X/Y analogues. [structure: see text]
Rodríguez-Escrich
Carles
C
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Av. Diagonal 647, 08028 Barcelona, Catalonia, Spain.
Olivella
Anna
A
Urpí
Fèlix
F
Vilarrasa
Jaume
J
D001965:Bromides / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D005663:Furans / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis*; D008956:Models, Chemical; D016566:Organoselenium Compounds / Q000737:chemistry; D013237:Stereoisomerism; D017967:Zinc Compounds / Q000737:chemistry; D000097442:Amphidinolides
D001965:Bromides; D005663:Furans; D018942:Macrolides; D016566:Organoselenium Compounds; D017967:Zinc Compounds; C480942:amphidinolide X; D000097442:Amphidinolides; C482967:amphidinolide Y; C018674:tetrahydrofuran; C093802:zinc bromide