1,3-Dipolar Cycloaddition Reaction of d-Glucose-Derived Nitrone with Allyl Alcohol:  Synthesis of 2-Hydroxy-1-deoxycastanospermine Analogues

Abstract

[reaction: see text] The synthesis and evaluation of glycosidase inhibitory activity of polyhydroxylated indolizidine alkaloids namely 2-hydroxy-1-deoxycastanospermine 3a,b and 2-hydroxy-1-deoxy-8a-epi-castanospermine 3c,d is reported. The key step involves the intermolecular 1,3-dipolar cycloaddition of allyl alcohol to d-glucose-derived nitrone 4, followed by tosylation, that afforded four diastereomeric sugar-substituted isoxazolidines 5a-d with the desired regioselectivity. The one-pot conversion of 5a-d to pyrrolidines 8a-d by hydrogenolysis, removal of 1,2-acetonoide functionality, and hydrogenation afforded corresponding target molecules 3a-d.

Unprecedented Synthesis of 4‐Ylidene (3 S)‐3‐hydroxy‐1‐aryl (alkyl)‐pyrrolidine‐2,5‐diones Based on 1,3‐Dipolar Cycloaddition of a Sugar‐derived Nitrone to N‐Substituted Maleimides

“…Interestingly, in the case of the ( Z )‐3‐hydroxyglycosyl‐ N ‐methylnitrone, the 1,3‐DC took place through an exo approach presumed to be favoured by a hydrogen bond between the pentose hydroxy group and one of the carbonyl of the N ‐arylmaleimide. With allyl alcohol as dipolarophile, 1,3‐CD with an analogous ( Z )‐3‐benzyloxyglycosyl‐ N ‐benzylnitrone afforded 4 different cycloadducts due to endo or exo approach to either the Re or Si faces of the nitrone …”

Antibacterial Activity, Quantitative Structure–Activity Relationship and Diastereoselective Synthesis of Isoxazolidine Derivatives Via 1,3‐Dipolar Cycloaddition of d‐glucose Derived Nitrone with Olefin

“…The oxygen of the 1,3-dipole 1a attacks the electron-deficient b-carbon of the olefin 2b to form the corresponding single endo-diastereoisomer 3b ( Table 1, entry 2, determined by crude 1 H NMR spectra) in good yield. Dhavale and Aouadi have reported the formation of exo isomer as the major product on reactions between nitrone and olefins with electron-donating substituents (25,45,46). We have employed olefins with electron-withdrawing substitution in our studies and obtained the endo isomer.…”

“…Isoxazolidines derived from carbohydrate based nitrones are potential intermediates for the synthesis of various aza sugars, on account of the presence of amino group in the masked form (19)(20)(21)(22)(23). Torrente et al, Karanjule et al and Jachak et al developed inter-and intramolecular 1,3-dipolar cycloaddition reactions of D-glucose-derived nitrone (22,25,26) and Datta et al reported the formation of oxepanes from intramolecular 1,3-dipolar cycloaddition of D-glucose-derived nitrone (27). Torrente et al, Karanjule et al and Jachak et al developed inter-and intramolecular 1,3-dipolar cycloaddition reactions of D-glucose-derived nitrone (22,25,26) and Datta et al reported the formation of oxepanes from intramolecular 1,3-dipolar cycloaddition of D-glucose-derived nitrone (27).…”

“…As a consequence, reports of nitrone cycloaddition continue to emerge in the literature using carbohydrates as a precursor, Shing et al (24) reported stereo-and regioselectivity in intramolecular nitrone-alkene cycloaddition of hept-6-enose derived from carbohydrates. Torrente (22,25,26) and Datta et al reported the formation of oxepanes from intramolecular 1,3-dipolar cycloaddition of D-glucose-derived nitrone (27). Coskun et al (28,29) reported dipolar cycloaddition of nitrone with N-arylmaleimides, which can be cited as example for 1,3 dipolar cycloaddition of nitrone with cyclic dienophiles.…”

Novel Galf-disaccharide mimics: synthesis by way of 1,3-dipolar cycloaddition reactions in water

“…The reaction gave the desired cycloaddition product 3, 13 resulting from an anti-exo cycloaddition stereochemistry, as the major product, in 49% (isolated) yield (dr P 92%, 1 H NMR of crude product). The isoxazolidine ring was reductively opened with Zn in the presence of catalytic copper acetate 14 to afford protected pseudo-disaccharide 4 in good yield. In order to reach disaccharide mimics, which more closely resemble the structure of the parent Galf disaccharides, we also investigated the cycloaddition of 1 with the 5-C-vinyl-L-arabinofuranoside derivative 5 15 ; the cycloaddition proceeded here highly stereoselectively and in a quite satisfactory yield to give the bicyclic product 6 (Scheme 2).…”