Studies on the Enantioselective Synthesis of <i>E</i>-Ethylidene-bearing Spiro[indolizidine-1,3′-oxindole] Alkaloids
Nihan Yayik,
Maria Pérez,
Elies Molins,
Joan Bosch,
Mercedes Amat
Affiliations
Nihan Yayik
Laboratory of Organic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain
Maria Pérez
Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, and Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
Elies Molins
Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Cerdanyola, Spain
Joan Bosch
Laboratory of Organic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain
Mercedes Amat
Laboratory of Organic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain
A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared.
