(5S)-5-Benzylswainsonines as potent and selective inhibitors of Golgi α-mannosidase II: synthesis, enzyme evaluation and molecular modelling.

Development of novel anti-cancer therapeutics based on Golgi α-mannosidase II (GMII) inhibition is considerably impeded by an undesired co-inhibition of lysosomal α-mannosidase leading to severe side-effects. In this contribution, we describe a fully stereoselective synthesis of (5S)-5-[4-(halo)benzyl]swainsonines as highly potent and selective inhibitors of GMII. The synthesis starts from a previously reported aldehyde readily available from l-ribose, and the key features include an intramolecular reductive amination with substrate-controlled stereoselectivity and a late-stage derivatisation of the benzyl group via ipso-substitution.

The Bucherer-Bergs Multicomponent Synthesis of Hydantoins-Excellence in Simplicity.

Hydantoins and their hybrids with other molecules represent a very important group of heterocycles because they exhibit diverse biological and pharmacological activities in medicinal and agrochemical applications. They also serve as key precursors in the chemical or enzymatic synthesis of significant nonnatural α-amino acids and their conjugates with medical potential. This review provides a comprehensive treatment of the synthesis of hydantoins via the Bucherer-Bergs reaction including the Hoyer modification but limited to free carbonyl compounds or carbonyl compounds protected as acetals (ketals) and cyanohydrins used as starting reaction components.