First Synthesis of Double Headed 1,3,4‐Oxadiazino[6,5‐b]indole AcycloC‐Nucleosides

Abstract

Condensation of 1,3-dihydro-2,3-dioxo-2H-indoles (la-c) with galactaric acid bis hydrazide (2) gave the corresponding galactaric acid bis[2-(1,2-dihydro-2-oxo-3H-indol-3-ylidene)hydrazides] (3a-c). Acetylation of the latter compounds with acetic anhydride in the presence of pyridine at ambient temperature gave the 2,3,4,5-tetra-O-acetylgalactaric acid bis[2-(1,2-dihydro-2-oxo-1-substituted-3H-indol-3-ylidene)hydrazides] (4b-d). Heterocyclization of the tetra-O-acetates 4b-d by heating with thionyl chloride afforded the double headed acyclo C-nucleosides: 1,2,3,4-tetra-O-acetyl- 1,4-bis[9-substituted-1,3,4-oxadiazino[6,5-b]indol-2-yl-1-ium]-galacto-tetritol dichlorides (5b-d). Structures of the prepared compounds were elucidated from their spectral properties.

New C-aryl alditols from Diels-Alder adducts of sugar nitroalkenes

“…[1][2][3][4][5][6][7][8] Thus, the nitrobenzene derivative chloramphenicol 1,2 inhibits protein synthesis, the methoxybenzene derivative karacilin 3 possesses antiviral activity in vitro against herpes viruses. This type of substances, namely C-aryl alditols, can be considered as acyclo-C-nucleoside analogues that by intramolecular dehydration could provide C-nucleosides; some of the latter, either natural or synthetic, have been reported to have a broad range of useful antitumor, antifungal and antibiotic properties, thus encouraging the development of methodologies toward this class of products.…”

“…This type of substances, namely C-aryl alditols, can be considered as acyclo-C-nucleoside analogues that by intramolecular dehydration could provide C-nucleosides; some of the latter, either natural or synthetic, have been reported to have a broad range of useful antitumor, antifungal and antibiotic properties, thus encouraging the development of methodologies toward this class of products. [8][9][10][11] Besides, the C-aryl alditol substructure is also present in some natural products, like the 5-(4-aminophenyl)-1,2,3,4-tetrahydroxypentane moiety of methanopterin, a cofactor involved in the biological reduction of CO 2 to CH 4 .…”

Ring Transformations of Pentose Glycals with Push-Pull Butadiene Functionality

“…Treatment of 2a, 2b with aromatic amines afforded the 1-aryl-5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydro-2-oxopyridine-3-carbonitriles 3a-c. Ring transformation of 1a, 1b with N-substituted oxobutyramides, dialkyl 3-oxopentanedioate and benzimidazol-2-ylacetonitrile yielded the 3-acetyl-1-aryl-5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydropyridin-2-ones 6a-d, alkyl 5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-2-hydroxyisophthalates 8a-d and 2-[1,2-bis(benzyloxy)-3-hydroxypropyl]benzo [4,5]imidazo-[1,2-a]-pyridine-4-carbonitriles 11a, 11b, respectively.Analogues of nucleosides in which an open-chain monosaccharide unit is linked via a C-C single bond to the heterocyclic part have received considerable attention in recent years due to their diverse biological properties. [1][2][3][4][5] We have previously reported the ring transformation reactions of 2-formyl glycals in the hexose series.…”

“…Treatment of 2a, 2b with aromatic amines afforded the 1-aryl-5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydro-2-oxopyridine-3-carbonitriles 3a-c. Ring transformation of 1a, 1b with N-substituted oxobutyramides, dialkyl 3-oxopentanedioate and benzimidazol-2-ylacetonitrile yielded the 3-acetyl-1-aryl-5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydropyridin-2-ones 6a-d, alkyl 5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-2-hydroxyisophthalates 8a-d and 2-[1,2-bis(benzyloxy)-3-hydroxypropyl]benzo [4,5]imidazo-[1,2-a]-pyridine-4-carbonitriles 11a, 11b, respectively.…”

“…[1][2][3][4][5] We have previously reported the ring transformation reactions of 2-formyl glycals in the hexose series. [6][7][8][9][10][11][12] Recently, the first reactions of pentose glycals with nitrogen nucleophiles to yield acyclo-C-nucleoside analogues were described.…”