Cyclisations and Strategies for Stereoselective Synthesis of Piperidine Iminosugars

Abstract

This personal account focuses on synthesis of polyhydroxylated piperidines, a subset of compounds within the iminosugar family. Cyclisations to form the piperidine ring include reductive amination, substitution via amines, iminium ions and cyclic nitrones, transamidification (N-acyl transfer), addition to alkenes, ring contraction and expansion, photoinduced electron transfer, multicomponent Ugi reaction and ring closing metathesis. Enantiomerically pure piperidines are obtained from chiral pool precursors (e. g. sugars, amino acids, Garner's aldehyde) or asymmetric reactions (e. g. epoxidation, dihydroxylation, aminohydroxylation, aldol, biotransformation). Our laboratory have contributed cascades based on reductive amination from glycosyl azide precursors as well as Huisgen azide-alkene cycloaddition. The latter's combination with allylic azide rearrangement has given substituted piperidines, including those with quaternary centres adjacent to nitrogen.

Stereoselective Synthesis of Nojirimycin α-C-Glycosides from a Bicyclic Acyliminium Intermediate: A Convenient Entry to N,C-Biantennary Glycomimetics

“…Most efforts on the chemistry side have been directed to devise efficient strategies matching the stereochemical and substitution profiles of the monosaccharides. 28 , 29 − 31 Replicating the glycosidic linkage distinctive of glycoconjugates, however, has proven much more challenging. The intrinsic instability of aminoacetal functionalities makes impractical the synthesis of iminosugar O -glycosides or of analogues having other heteroatom substituents at the pseudoanomeric position.…”

Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance

“…Several reviews on the topic of multivalent iminosugars have been published; however, large parts deal with the synthesis and biological properties of multivalent piperidine iminosugars rather than pyrrolidine [ 12 , 14 , 71 , 72 ]. Moreover, the latter research field was scarcely reviewed in the decade of its rapid development (2012–2022) [ 73 ].…”

Exploiting angled thin film vortex microfluidics for expeditious syntheses of iminosugars

“…18 As a result of the biological importance of iminosugars, there have been a number of syntheses published to date. 9,20 Here we describe the use of the VFD in developing a microuidic-based platform to synthesis iminosugars, using a simple yet robust synthesis, in a timely and efficient manner. A synthetic methodology that we were drawn to involves the use of 1,5-dicarbonyl compounds, which are easy to prepare, and have been shown to be a useful synthon in preparing iminosugars of various types 8,[21][22][23][24][25] and specically the work of Baxter and Reitz who developed a synthesis of iminosugars using this approach (Fig.…”