An Efficient and Practical Chemoenzymatic Route to (3R,3aR,6R,6aR)-Hexahydrofuro[3,2-b]furan-6-amino-3-ol (6-Aminoisomannide) from Renewable Sources

Abstract

The synthesis of 6-aminoisomannide is easily achieved starting from the renewable, inexpensive and commercially available isosorbide, in 66% overall yield. A biocatalysed highly regioselective acetylation of the 3-endo hydroxyl group of isosorbide was followed by the stereospecific interconversion of the 6-exo hydroxyl group into azido group, through reaction with trifluoromethanesulfonic anhydride followed by nucleophilic displacement of the triflate group by sodium azide. Finally, reduction of the azido group and deacetylation of the 3-hydroxy group were performed one pot by using LiAlH4.

Renewable Resources for Enantiodiscrimination: Chiral Solvating Agents for NMR Spectroscopy from Isomannide and Isosorbide

“…While monoderivatization of symmetric isomannide 1 led to one product, reaction of isosorbide 2 afforded a mixture of the two possible isomers 5 and 6 in an ∼1:1 ratio. The nonselective monoderivatization of isosorbide was not an issue, since we were interested in both isomers; a selective derivatization could be easily obtained exploiting an initial selective protection as reported in the literature. , In all cases, pure compounds were obtained in good yields after chromatographic purification, with the only exception of 4a – d , 7a – c that crystallized from the crude and/or were recrystallized after a simple workup.…”

“…In our previous works, we demonstrated that some isohexide derivatives could be successfully employed as CSAs in NMR studies. 32 , 33 These positive preliminary results prompted us to expand the scope, synthesizing new isohexide derivatives to be employed in NMR enantiodiscrimination studies ( Figure 2 ). In particular, derivatization of the hydroxyl groups as arylcarbamates was chosen to obtain new chiral shift agents that could establish multiple intermolecular interactions, such as π–π interactions through the aromatic groups and dipole–dipole interactions and/or hydrogen bond interactions through the carbamoyl group.…”

“…Due to these characteristics, isohexides were successfully employed as starting materials in the preparation of chiral ligands, 24 organocatalysts, 25 and chiral ionic liquids. 26,27 In particular, starting from isomannide, bidentate ligands 24,28−30 and ionic molecular tweezers 27,31 were obtained by virtue of the endo arrangement of the hydroxyl groups, which allows the appended units to be sufficiently close to each other. However, the interaction of two appended moieties was even observed in some isosorbide derivatives, due to their particular spatial arrangement.…”

“…However, the interaction of two appended moieties was even observed in some isosorbide derivatives, due to their particular spatial arrangement. 31 In our previous works, we demonstrated that some isohexide derivatives could be successfully employed as CSAs in NMR studies. 32,33 These positive preliminary results prompted us to expand the scope, synthesizing new isohexide derivatives to be employed in NMR enantiodiscrimination studies (Figure 2).…”

Control of Molecular Packing in Crystal and Electron Communication of Two Ferrocenyl Moieties across Chiral Isomannide or Isosorbide Bridge

“…These functional groups can be easily derivatized, to obtaining a plethora of derivatives whose properties depend both from the characteristics of the introduced functional groups and from the different stereochemical arrangement of the hydroxyl groups [23,[26][27][28][29]. In previous studies [30][31][32][33][34][35], some of us successfully employed these compounds as starting materials for the synthesis of new chiral auxiliaries [30][31][32][33] and light-emitting materials [34]. These studies highlighted the importance of the chiral backbone, which leads to an interaction between the functional groups linked to the central scaffold, with a great influence on the final properties, both in isomannide 1 and isosorbide 2.…”