The synthetic methods to build the 2,6-disubstituted piperidine structural motif were described focusing on stereochemical control of two substituents at C2 and C6 with specific examples of natural products.

Alkylative ring-opening of bicyclic aziridinium ion generated from 4-hydroxybutylaziridine with organocopper reagent was achieved successfully to afford 2-alkylsubstituted piperidine in high or moderate yield. This method allowed carbon-carbon bond formation of “non-activated” aziridine via aziridinium ion ring-opening in regio- and stereo-selective manner for the first time. This newly developed reaction was applied for an efficient synthesis of alkaloid with the representative example of conine and epiquinamide.

The classical Prins cyclization has been one of the most intensively studied reactions during the last two decades, and it has found many applications in key steps of natural product syntheses, especially for products containing tetrahydropyran motifs and related structures in their core skeletons. The application of this reaction to the synthesis of spirocylic networks has made substantial progress recently. Spiro motifs are found in many natural products with promising biorelevance and are increasingly being incorporated in drug candidates. Further, various spirocyclic chiral ligands have shown promising efficiency in asymmetric synthesis. Here a compilation of recent spiroannulation reactions by Prins cyclization is presented, focusing on the scope and versatility of this method.

The first expedient asymmetric synthesis of both enantiomers of 5,6-dihydrouracil-type marine natural products biemamides B and D was achieved from chiral 1-(α-methylbenzyl)­aziridine-2-carboxylate. The key steps involved in the synthetic route are regio- and stereoselective aziridine ring opening via azide followed by a base-induced cyclization reaction. After comparison of ECD and optical rotation data of both synthetic enantiomers, the absolute configuration of natural biemamides B and D at the C5 position has been assigned as (−)-(5S), which is an enantiomer to the originally proposed structure (−)-(5R).