Novel Cyclic Sugar Imines:  Carbohydrate Mimics and Easily Elaborated Scaffolds for Aza-Sugars

Abstract

[reaction: see text] Representative simple or polyhydroxylated, pyrrolidine (e.g, DRAM) or piperidine (e.g., DNJ) imines not only are potential carbohydrate-processing enzyme inhibitors that may be formed as regioisomeric variants but also are scaffolds that may be rapidly elaborated to diversely functionalized aza-sugars through highly diastereoselective organometallic additions.

Highly Diastereoselective Additions to Polyhydroxylated Pyrrolidine Cyclic Imines: Ready Elaboration of Aza‐Sugar Scaffolds To Create Diverse Carbohydrate‐Processing Enzyme Probes

“…This inhibition of the D,L galactosidase/ fucosidase enzyme pair by erythritol family 34 is, as for the threitol family 33, partially consistent with configurational mimicry of the cis-diol OH-3,4 unit of galactosidase/fucosidase by the cis-diol OH-2,3 unit of 34 ( Figure 4). Consistent with these results, methyl erythritol aza-sugar 34 a has previously been shown to be a good inhibitor of a-lfucosidase (K i 2.0 mm), [22] although this activity is modest compared with some of the most potent a-l-fucosidase azasugar inhibitors known (for example, the piperidine DFJ, the l-fuco analogue of DNJ, displays a K i of 0.029 mm towards the same enzyme [50] ). Thus, again the Fleet mirror-image postulate correctly predicts the observed additional inhibition of agalactosidase by this family of racemates.…”

“…Some initial aspects of this work have previously appeared in a brief communication. [22] Additionally, these imines allow access to scaffolds similar to those found in natural products of known activity, such as anisomycin 5, a clinically proven peptidyl-transferase inhibitor, which exhibits strong and selective activity against pathogenic protozoa and fungi. [23] This paper demonstrates that this methodology may be applied to the addition of a variety of functional groups with excellent diastereoselectivities and in good to excellent yields beyond those previously observed for cyclic imines.…”

Development and pharmacologic characterization of deoxybromophospha sugar derivatives with antileukemic activity

“…Replacement of the oxygen atom in the hemiacetal ring of normal sugars by a carbon or heteroatom leads to the formation of pseudo-sugars, several of which have been heavily investigated in the fields of synthetic, biological, and medical chemistry [3]. Novel nucleoside derivatives of pseudo-or hetero-sugars reported to date include aza-sugar (nitrogen instead of an oxygen atom; amino sugar) [4][5][6][7], thio-sugar (or thia-sugar; sulfur instead of an oxygen atom) [8,9], and carba-sugar (oxygen atom replaced by a methylene group) [10,11]. Further, the potential bioactivity of hetero-sugar nucleosides and glycosides (e.g., glycosidase and nojirimycin) has also been reported [12].…”

The Reaction of N-Isocyaniminotriphenylphosphorane with Cyclopentanone and A Primary Amine in the Presence of An E-Cinnamic Acid Derivative

“…To the best of our knowledge, this is the first report in which N-isocyaniminotriphenylphosphorane is participated in a four-component condensation reaction in the presence of cyclopentanone followed by an intramolecular aza-Wittig, 21,22 ring closure of the iminophosphorane moiety with the ester carbonyl. Finally, we are reporting a new IMCRs, 23 yielding 2,5-disubstituted 1,3,4-oxadiazole derivatives, by a sequence of a multicomponent reaction, and an intramolecular aza-Wittig closure.…”