Spiro Iminosugars: Structural Diversity and Synthetic Strategies

Abstract

From their discovery in the late 1960's, iminosugars have undergone an expansion from an area of science limited to a few researchers to a field that now attracts the interest of members of the whole synthetic organic chemistry community. Indeed, many tasks concern structural modifications of standard iminosugars in order to improve their biological and pharmacological properties. In this way, the introduction of an adjoining spiro cycle afforded unprecedented polyhydroxyazaspiranes, the structures and syntheses of which are presented in this chapter. Special attention is paid to the key steps involved in the generation of the pivotal quaternary spiro-atom.

From Sweet Molecular Giants to Square Sugars and Vice Versa

“…In parallel with our studies on multivalency, we have continued to enjoy designing ‘small’ molecules with a focus on conformationally constrained glycomimetics. 103 104 Our studies have aimed at exploring unfrequented regions of glycochemical space, while giving the opportunity to address new synthetic challenges. Constraining a given structure in orientations that fit the binding site of the biological target is a popular strategy in drug discovery.…”

Evaluation of Nonnatural L-Iminosugar C,C-Glycosides, a New Class of C-Branched Iminosugars, as Glycosidase Inhibitors

“…To exploit further the synthetic potential of these iminosugar C,C-glycosides, those bearing two terminal alkenes at the pseudoanomeric position were converted into the corresponding spirocyclic iminosugars that are scarce in the literature. 30,31,32 Indeed, the a-L-fucosidase inhibitory potency in the low micromolar range exhibited by derivatives 3a and 3b 33,34 (Scheme 2a) encouraged us to access structural analogues bearing a pseudoanomeric five-or sixmembered ring imposed by the alkene chain length. The RCM of C,C-diallyl iminosugar 1e and previously reported C-allyl, C-homoallyl iminosugar 1f 28 using Grubbs' II catalyst in dichloroethane at 50°C furnished the corresponding bicycles 4a and 4b in satisfactory 62% to 78% yields respectively.…”

Amino Acid-Based Synthesis and Glycosidase Inhibition of Cyclopropane-Containing Iminosugars

“…Herein, we envisioned the preparation of novel bicyclic iminosugars that include the cyclopropane motif fused with piperidine starting from the natural amino acid l -serine as the chiral pool. The final compounds present five stereogenic centers, and the synthesis involves the inversion of the configuration of the starting l -serine ( S -configuration) into the C5 configuration of d -carbohydrates ( R ) . Preliminary glycosidase inhibition evaluation is shown.…”