Seven-Step Synthesis of All-Nitrogenated Sugar Derivatives Using Sequential Overman Rearrangements.

All-nitrogenated sugars (ANSs), in which all hydroxy groups in a carbohydrate are replaced with amino groups, are anticipated to be privileged structures with useful biological activities. However, ANS synthesis has been challenging due to the difficulty in the installation of multi-amino groups. We report herein the development of a concise synthetic route to peracetylated ANSs in seven steps from commercially available monosaccharides. The key to success is the use of the sequential Overman rearrangement, which enables formal simultaneous substitution of four or five hydroxy groups in monosaccharides with amino groups. A variety of ANSs are available through the same reaction sequence starting from different initial monosaccharides by chirality transfer of secondary alcohols. Transformations of the resulting peracetylated ANSs such as glycosylation and deacetylation are also demonstrated. Biological studies reveal that ANS-modified cholesterol show cytotoxicity against human cancer cell lines, whereas each ANS and cholesterol have no cytotoxicity.

Crystal structure of (-)-methyl (R,E)-4-[(2R,4R)-2-amino-2-tri-chloro-methyl-1,3-dioxolan-4-yl]-4-hy-droxy-2-methyl-but-2-enoate.

In the title compound, C10H14Cl3NO5, the five-membered dioxolane ring adopts an envelope conformation with the C atom bonded to the butenoate side chain as the flap. It deviates from the mean plane of the other atoms in the ring by 0.446 (6) Å. In the crystal, mol-ecules are connected by O-H⋯O hydrogen bonds into helical chains running along the b-axis direction. The chains are linked into a sheet structure parallel to (001) by an N-H⋯O hydrogen bond. These classical hydrogen bonds enclose an R44(24) graph-set motif in the sheet structure. Furthermore, a weak inter-molecular C-H⋯Cl inter-action expands the sheet structures into a three-dimensional network.