Aziridines as a structural motif to conformational restriction of azasugars

Abstract

In order to investigate the hypothesis that the glycosidase inhibitor isofagomine was bound to alpha- or beta-glucosidase in a 1,4B conformation, a number of bicyclic aziridines that adopt the 1,4B or B1,4 conformations were synthesised and investigated. (1R)-2-endo,3-exo-2,3-Dihydroxy-4-endo-4-hydroxymethyl-6- azabicyclo[3.1.0]hexane (5) and its N-methyl and N-benzyl analogues and (1S)-2-exo-3-endo-2,3-dihydroxy-4- endo-4-hydroxymethyl-6-azabicyclo-[3.1.0]hexane (6) were synthesised. The aziridines 5 and 6 were found to be weak or not inhibitors of alpha-glucosidase, beta-glucosidase and alpha-fucosidase.

The Synthesis of Cyclophellitol‐Aziridine and Its Configurational and Functional Isomers

“…The above schemes represent all configurational and functional cyclophellitol‐aziridines (namely, 1 , 12 , 31 , 32 , and 39 ) whose synthesis has been reported to date. Studies on the synthesis of related compounds exists, however, both targeting cyclopentitol‐aziridines (not shown here) and in particular conduritol‐aziridines (Scheme ).…”

Rational Design of Mechanism-Based Inhibitors and Activity-Based Probes for the Identification of Retaining α-l-Arabinofuranosidases

“…No route to the synthesis of covalent inhibitors of α- l -arabinofuranosidases has previously been identified. The first synthesis of covalent furanose-configured inhibitors was the preparation of β- d -arabinofuranosyl and α- l -xylofuranosyl aziridines reported by Bols et al in 2003 . These were prepared via N–O reduction of cyclopentaisoxazolidines.…”

“…The first synthesis of covalent furanose-configured inhibitors was the preparation of β-D-arabinofuranosyl and α-L-xylofuranosyl aziridines reported by Bols et al in 2003. 21 These were prepared via N−O reduction of cyclopentaisoxazolidines. Due to the inverted stereochemistry of the electrophilic moiety with respect to C4 (carbohydrate numbering), this synthetic strategy cannot be translated to α-L-arabinofuranose analogues, so new synthetic methodologies are needed to expand the scope of synthetically accessible furanoside mimics.…”

An overview of key routes for the transformation of sugars into carbasugars and related compounds

“…Catalytic hydrogenation afforded aziridine 206a, which finally gave 206b after removal of the protecting groups (Scheme 45). 94 Recently, an intramolecular ketonitrone-olefin cycloaddition reaction was used for the synthesis of aminocyclopentitol 209 (Scheme 46). 95 Using a 1,3-dipolar reaction as the key step, Gallos and co-workers synthesised ent-gabosine E. Condensation of N-methylhydroxylamine with lactol 210a led to the formation of cycloadducts 211 and 212 in a 2:1 ratio (Scheme 47), via the corresponding nitrone.…”