Preparation of glycosides of 2-deoxy-2-methylamino-D-mannose, 2-deoxy-2-methylamino-D-glucose,and 2-deoxy-2-methylamino-D-galactose: observations on N-methylation of amides

Benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-α-D-mannopyranoside (10) and its furanose isomer (9), the derived N-methyloxazolidinones 11 and 6, benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-β-D-glucofuranoside (15) and methyl 2-deoxy-2-methylacetamido-β-D-galactofuranoside (20), were prepared from appropriate diethyl dithioacetals. They were considered the most suitable starting materials for synthesis of O-methyl-2-deoxy-2-methylamino-hexoses because of their ease of preparation and the presence of suitable blocking groups. Oxazolidinones were prepared from N-benzyloxycarbonyl derivatives of 2-amino-2-deoxy-D-mannose by using methanolic sodium methoxide. Their use in preparation of 2-deoxy-2-methyl-amino derivatives is discussed. The Kuhn reagent was used in these syntheses for N-methylating amides. However, certain amides containing comparatively bulky substituents in the vicinity of the NH group are resistant to methylation.     

5-deoxy-5-fluoro-L-sorbose originating from 2-deoxy-2-fluoro-D-glucitol by fermentation withAcetomonas oxydans

Using fermentation with a selected strain ofAcetomonas oxydans it was possible to convert 2-deoxy-2-fluoro-D-glucitol to 5-deoxy-5-fluoro-L-sorbose, in agreement with Bertrand’s and Hudson’s rule. The last-named compound was isolated in a yield of 88%. Both compounds were little toxic againstAcetomonas oxydans. Part VIII of the serios Biochemical Dehydrogenation of Saccharides.     

Synthesis of 2-acetamido-2-deoxy-5-thio-d-glucopyranose

2-Acetamido-2-deoxy-5-thio-d-glucopyranose (12) has been synthesized from methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside (1). Benzoylation of 1, followed by O-deisopropylidenation, gave methyl 2-acetamido-3-O-benzoyl-2-deoxy-β-d-glucofuranoside, which was converted, via selective benzoylation and mesylation, into methyl 2-acetamido-3,6-di-O-benzoyl-2-deoxy-5-O-mesyl-β-d-glucofuranoside (5). Treatment of 6, formed by the action of sodium methoxide in chloroform on 5, with thiourea gave methyl 2-acetamido-2,5,6-trideoxy-5,6-epithio-β-d-glucofuranoside (7), which was converted into the 5-thio compound 9 by cleavage of the epithio ring in 7 with potassium acetate. Alkaline treatment of 10, derived from 9 by hydrolysis, afforded the title compound. Evidence in support of the structures assigned to the new derivatives is presented.     

Total syntheses and cytotoxicity of kealiiquinone, 2-deoxy-2-aminokealiiquinone and analogs

Concise syntheses of two Leucetta-derived naphthimidazole alkaloids, kealiiquinone and 2-deoxy-2-aminokealiiquinone, are described based on a biosynthetic-guided hypothesis. Advanced intermediates containing the full naphthimidazole framework are constructed through Friedel–Crafts chemistry followed by oxidation of the electron rich C-ring with hydrogen peroxide. The cytotoxicity of these alkaloids in a breast cancer cell line along with several closely related marine-derived natural products kealiinines A–C and analogs are reported.     

Synthesis of 2-acetamido-2-deoxy-4-O-alpha-L-fucopyranosyl-alpha-D-glucopyranose]

Condensation of 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide with benzyl 2-acetamido-3,6-di-O-benzyl-alpha-D-glucopyranoside in dichloromethane-N,N-dimethylformamide, in the presence of tetraethylammonium bromide, diisopropylethylamine, and molecular sieve (halide ion-catalyzed reaction), gave benzyl 2-acetamido-3,6-di-O-benzyl-2 deoxy-4-O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-alpha-D-glucopyranoside in crystalline form in 82% yield. Hydrogenolysis of the benzyl groups gave the title disaccharide, in crystalline form in 90% yield, which was characterized by a crystalline peracetylated alpha-D derivative.     

Nucleosides having acyclic 2-deoxy-1-thio- -arabino-hexitol and 2-deoxy-1-thio- -erythro-pentitol chains

Aspects of the pyrolysis of 1-deoxy-1-glycino-d-fructose and 1-β-alanino-1-deoxy-d-fructose are reported. Thermal analysis and parallel chemical investigations demonstrate that formation of these Amadori compounds provides a low-energy route to the thermal degradation of their amino acid and sugar moieties. Furthermore, the pathway leads to the production of increased quantities of various aroma compounds as compared with controls. Pyrolysis of the 1-amino-l-deoxyketoses also produces the toxic compound protoanemonin; a degradation pathway leading to its formation is proposed.     

Synthesis of enantiomerically pure, sn-1 modified sn-2-deoxy-2-amido-glycero-3-phospholipids

The synthesis of two types of enantiomerically pure sn-2-deoxy-2-amido-glycero-phospholipids differing in the connection of the alkyl chain at the sn-1-position is described. Both types of lipids were prepared from L-serine-methylester as the chiral starting material.     

A practical synthesis of 2-deoxy-2-fluoro-D-arabinofuranose derivatives.

A seven-step synthesis of 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose, a versatile intermediate in the synthesis of chemotherapeutically important nucleosides, was achieved from 1,2:5,6-di-O-isopropylidene-3-O-tosyl-alpha-D-allofuranose. The crucial steps were the fluorination by use of potassium fluoride in acetamide and the conversion of 6-O-benzoyl-3-deoxy-3-fluoro-D-glucofuranose into 5-O-benzoyl-2-deoxy-2-fluoro-3-O-formyl-D-arabinofuranose by periodate oxidation. Also described is the synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosine. This procedure affords good overall yields of products without formation of undesirable, isomeric intermediates and is suitable for large-scale preparations.