Tryptophanol-derived oxazolopiperidone lactams: Valuable building blocks for the enantioselective synthesis of piperidine-containing alkaloids

Abstract

Chiral oxazolopiperidone lactams are known to be valuable building blocks for the synthesis of enantiopure piperidines bearing virtually any type of substitution pattern,including diverse natural products and bioactive compounds. These lactams are synthesized by cyclocondensation of prochiral or racemic δ-oxo (di)esters with the chiral amino alcohol. Generally phenylglycinol is used as the amino alcohol and a final debenzylation is needed. In this review it is presented the use of (S)-tryptophanol as the chiral amino alcohol for the construction of complex piperidine-containing derivatives. The starting lactams are easily accessible, with very high stereoselectivities, by a cyclocondensation reaction of (S)-tryptophanol with an appropriate prochiral or racemic δ-oxo (di)esters. Finally, cyclization of the chiral oxazolopiperidone lactams provides a straightforward route to enantiopure indolo[2,3-a]quinolizidine skeleton and, by simply modulating the reactivity of the indole ring by tosylation, allows the synthesis of enantiopure spiro[indole-3,3’-indolizidine] skeleton.