Synthesis of All Configurational Isomers of 1,6-Anhydro-2,3,4-trideoxy-2,3-epimino-4-fluoro-β-d-hexopyranoses

Abstract

We have prepared a full series of 1,6-anhydro-2,3,4-trideoxy-4-fluoro-2,3-epimino-beta-d-hexopyranoses. The key step was the reaction of azido sulfonates possessing a free C-4 hydroxyl with DAST and subsequent LiAlH(4) reduction. Nucleophilic displacement of the hydroxyl activated by DAST proceeded without rearrangement and with moderate to good yields. A convenient synthesis of d-mannoepimine from a readily available 3-benzylamino derivative was also developed.

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

“…Regioselective azidolysis [ 21 , 35 – 36 ] of 10 yielded 2-azido alcohol 11 which was converted to 12 by benzoylation at O-3 and debenzylation at O-4. To prevent azide reduction, oxidative debenzylation [ 24 ] was applied instead of the more common hydrogenation. Debenzylation of 10 gave dianhydro derivative 13 [ 34 , 37 ] (available also directly from D-glucal [ 31 , 33 ] or from levoglucosan [ 38 ]) which was converted to 14 by Latrell–Dax inversion at C-4 [ 39 ].…”

“…The elaborated chemistry of 1,6-anhydrohexopyranose derivatives is suitable for this purpose [ 21 – 23 ]. Building on previous results from our [ 24 ] and other groups [ 25 – 28 ], we designed an approach based on stereoselective introduction of an azide as a masked amine group at C-2, and fluorine at C-3 and C-4 by nucleophilic displacement. Resulting 3-fluoro, 4-fluoro, and 3,4-difluoro analogs of 2-azido-1,6-anhydrohexopyranoses were then converted into the target fluoro analogs of D-glucosamine and D-galactosamine ( Scheme 1 ).…”

The Dinosyl Group: A Powerful Activator for the Regioselective Alcoholysis of Aziridines

“…N-Activated aziridines are versatile synthetic intermediates [1][2][3] (e.g., several syntheses of Oseltamivir [4] ) and easily accessible from amino alcohols, [5][6][7][8][9] from carbene attack on imines (aza-Darzens reaction), [10] or by direct aziridination of alkenes. [11][12][13][14] Although aziridines are close analogs to epoxides, substitution at the nitrogen atom offers an additional handle for tuning their reactivity.…”

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

“…Also, we did not observe any 1,2-alkyl shift of C6 from C5 to C4 with enlargement of the dioxolane ring followed by fluorine introduction at C5 (compound 20, step e) [33]. This known alkyl shift [29,39] is usually displayed by more carbocationic character of the intermediate species [40]. In our case, the polyfluoroalkyl group could destabilize the adjacent carbocation center [41][42][43], avoiding 1,2-alkyl shift, and thus formation of byproduct 20.…”