Chiral oxazolopiperidone lactams: versatile intermediates for the enantioselective synthesis of piperidine-containing natural products.
Phenylglycinol-derived oxazolopiperidone lactams are exceptionally versatile building blocks for the enantioselective construction of structurally diverse piperidine-containing natural products and bioactive compounds. These lactams are readily available in both enantiomeric series by cyclocondensation of the chiral amino alcohol with a delta-oxo acid derivative and allow the substituents to be introduced at the different ring positions in a regio- and stereocontrolled manner, providing access to enantiopure polysubstituted piperidines bearing virtually any type of substitution pattern, and also quinolizidines, indolizidines, perhydroquinolines, hydroisoquinolines, as well as complex indole alkaloids. Of particular interest are cyclocondensation reactions with racemic or prochiral delta-oxo (di)acid derivatives in processes involving dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups, as they directly lead to lactams that already incorporate the carbon substituents on the heterocyclic ring. The use of (S)-3,4-dimethoxyphenylalaninol or (S)-tryptophanol in the above cyclocondensation reactions expands the potential and the scope of the methodology, providing a straightforward route to enantiopure benzo[a]- and indolo[2,3-a]quinolizidines.
Escolano
Carmen
C
Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Amat
Mercedes
M
Bosch
Joan
J
D000470:Alkaloids / Q000138:chemical synthesis*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001688:Biological Products / Q000138:chemical synthesis*; D003500:Cyclization; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis*; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis*; D011728:Pyridones / Q000138:chemical synthesis*; D011807:Quinolizines / Q000138:chemical synthesis; D013237:Stereoisomerism
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001688:Biological Products; D006574:Heterocyclic Compounds, 2-Ring; D007769:Lactams; D010080:Oxazoles; D011728:Pyridones; D011807:Quinolizines; C508120:oxazolopyridinone; D009584:Nitrogen