Nitrone Cycloadditions to Isolevoglucosenone:  Ready Access to a New Class of Directly Linked (1→3)-Imino-C-disaccharides

Abstract

Straightforward access to a new class of d-gulo- and d-allo-derived directly linked (1-->3)-imino-C-disaccharides by means of cycloaddition reactions of enantiopure polyhydroxylated pyrroline N-oxides with isolevoglucosenone is reported. The cycloaddition reactions display a high level of double asymmetric induction, which allows a partial kinetic resolution of a racemic nitrone. [reaction: see text]

Synthesis of Aza-C-disaccharides (Dideoxyimino-alditols C-Linked to Monosaccharides) and Analogues

“…Shortly after, further examples of branched aza-C-disaccharides were presented by Johnson, 39 and more recently by Mootoo 35 and Argyropoulos. 40 Pseudo aza-C-disaccharides (no linker between the two monosaccharide analogues: X = no atom) have been obtained by Cardona et al [41][42][43][44] In our group, Cardona realized the syntheses of homo-(1→3)-C-linked iminodisaccharides, with X = CH 2 CH= , 45 and X = -CH 2 CH 2 -, 46 Figure 3). Interest in these disaccharide mimetics is to find more potent and more specific glycosidase or/and glycosyltransferase inhibitors as they may provide potential drugs in new therapy strategies, for instance against HIV 47 and cancer, 48 or to generate immunostimulatory agents 49 as well as haptens for the generation of catalytical antibodies.…”

Current applications of kinetic resolution in the asymmetric synthesis of substituted pyrrolidines

“…Imino-C-disaccharide precursors featuring a trisubstituted pyrrolidine subunit were synthesised by Cardona and coworkers (Scheme 29). 88,89 A partial kinetic resolution of racemic five-membered ring nitrone (±)-cis-112 was achieved in a 1,3diploar cycloaddition with isolevoglucosenone 114. 88 Moderate enantioselectivity was obtained for the recovered nitrone.…”

“…88,89 A partial kinetic resolution of racemic five-membered ring nitrone (±)-cis-112 was achieved in a 1,3diploar cycloaddition with isolevoglucosenone 114. 88 Moderate enantioselectivity was obtained for the recovered nitrone. They adapted this method, employing both levoglucosenone 115 and its isomer 114, to achieve a parallel kinetic resolution (PKR) obtaining two distinct products in moderate to good yields.…”

Quasienantiomeric Levoglucosenone and Isolevoglucosenone Allow the Parallel Kinetic Resolution of a Racemic Nitrone

“…We noticed that levoglucosenone ( 1 ) and isolevoglucosenone ( 2 ) are quasienantiomers, 1c, and we envisaged that they could be ideal substrates to be used in PKR experiments. We report here our results on the parallel kinetic resolution (PKR) of a racemic nitrone 3 with 1 and 2 en route to the stereodivergent synthesis of imino- C -disaccharide precursors 1 Dipolarophiles and nitrones employed. …”

“…The activated double bond in levoglucosenone ( 1 ) and isolevoglucosenone ( 2 ) ensures a high reactivity and regioselectivity in 1,3-dipolar cycloadditions. However, while cycloadditions of nitrones and nitrile oxides to 1 have been reported early by Paton and co-workers, use of 2 in cycloaddition chemistry has been proved only recently …”