The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as α-l-fucosidase inhibitors.

The ability of a series of pyrrolidines to inhibit several glycosidases was investigated. Using Fleet's 'mirror-image postulate', it was proposed that enantiomeric derivatives of 1,4-dideoxy-1,4-imino-d-lyxitol (a known α-d-galactosidase inhibitor) would show inhibitory activity against α-l-fucosidases. Some modest α-l-fucosidase inhibitory activity was observed for selected compounds (particularly an aminomethyl pyrrolidine) and it was proposed that better activity could be obtained by modifying the C-2 side chain of the pyrrolidine core. The d-galacto carbamate scaffold also exhibited somewhat selective, albeit modest, α-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development.

I(2)-mediated carbamate annulation: scope and application in the synthesis of azasugars.

The I(2)-mediated carbamate annulation provides an efficient and highly stereoselective route for the synthesis of a variety of pyrrolidines and piperidines, both in the presence and absence of protecting groups. Evidence for the formation of an iodoamine intermediate during the annulation is provided and, for the first time, we explore possible mechanisms of the annulation. The high cis-selectivity of the carbamate annulation is also compared to other N-halocyclisations and aminomercurations and some general conclusions about the diastereoselectivity of these types of reactions are made.

Stereoselective total synthesis of aminoiminohexitols via carbamate annulation.

New methodology for the preparation of a variety of aminoiminohextitols is described. Key in the synthesis is the application of a diastereoselective Strecker reaction and the extension of our carbamate annulation methodology to protected and functionalized alkenylamines. Insight into the effects that the substitution patterns of the alkenylamines have on the diastereoselectivity of the iodocyclization and carbamate annulation is discussed. An evaluation of the glycosidase inhibitory activity of the aminoiminohexitols and derivatives is also presented, with the previously undisclosed D-talo isomer showing good selective inhibition of ß-D-glucosidase.

Protecting-group-free synthesis of amines: synthesis of primary amines from aldehydes via reductive amination.

New methodology for the protecting-group-free synthesis of primary amines is presented. By optimizing the metal hydride/ammonia mediated reductive amination of aldehydes and hemiacetals, primary amines were selectively prepared with no or minimal formation of the usual secondary and tertiary amine byproduct. The methodology was performed on a range of functionalized aldehyde substrates, including in situ formed aldehydes from a Vasella reaction. These reductive amination conditions provide a valuable synthetic tool for the selective production of primary amines in fewer steps, in good yields, and without the use of protecting groups.