DFT Based Comparative Studies of Some Glucofuranose and Glucopyranoside Esters and Ethers

Carbohydrate-based molecular scaffolding received significant interest due to its impact on the drug discovery and development in synthetic carbohydrate chemistry during the last couple of decades. In this respect, four glucose compounds in the furanose and pyranose forms with ester and ether functionality were selected for their structural, thermodynamic and chemical reactivity studies. PASS predication indicated that the glucose in the six-membered pyranose form was more prone to biological properties compared to their five-membered furanose form. Also, in the pyranose form acetate ester (3) had more potentiality than the ethyl ether (4). The HOMO-LUMO energy gaps were almost similar for both monosubstituted furanose and pyranose glucose indicating their almost similar reactivities. It was also inferred that these 6-O-substituted compounds followed Lipinski’s rule with the acceptable range of ADMET levels, and hence, safe from lethal proarrhythmic risks. Hopefully, these results can be used in the near future for their probable pharmaceutical use without any remarkable toxicity.

Towards consistency in geometry restraints for carbohydrates in the pyranose form: modern dictionary generators reviewed

: Macromolecular restrained refinement is nowadays the most used method for improving the agreement between an atomic structural model and experimental data. Restraint dictionaries, a key tool behind the success of the method, allow fine-tuning geometric properties such as distances and angles between atoms beyond simplistic expectations. Dictionary generators can provide restraint target estimates derived from different sources, from fully theoretical to experimental and any combination in between. Carbohydrates are stereochemically complex biomolecules and, in their pyranose form, have clear conformational preferences. As such, they pose unique problems to dictionary generators and in the course of this study, require special attention from software developers. Functional differences between restraint generators will be discussed, as well as the process of achieving consistent results with different software designs. The study will conclude a set of practical considerations, as well as recommendations for the generation of new restraint dictionaries, using the improved software alternatives discussed.

Formation of lipid tubules induced by a sugar-like molecule myo-inositol

The sugar-like molecule myo-inositol (InOH) bears an uncanny structural resemblance to the pyranose form of the sugar ᴅ-glucose (DG). InOH and its derivatives play a pivotal role in cell biology...

SYNTHESIS OF CARBOHYDRATE BLOCKS FOR 2'.3'-DIDEOXYNUCLEOSIDES FROM LEVOGLUCOSENONE

Nucleosides containing five-membered deoxy-carbohydrates in the glycosidic part, such as zalcitabine, 2'.3'-dideoxyuridine, stavudine, are widely used in acquired immunodeficiency syndrome (AIDS). A number of 2'.3'-dideoxynucleosides is an effective inhibitor of type-1 immunodeficiency virus (HIV-1) in humans. Levoglucosenone and cyrene (dihydrolevoglucosenone) are unique compounds, optically pure ketones of carbohydrate nature obtained from renewable bio-raw materials and available by pyrolysis of any cellulose-containing materials. They are promising carbohydrates for the production of modified nucleosides; in addition, they are commercially available. Based on levoglucosenone, we synthesized chiral carbohydrate blocks for dideoxy-nucleosides, namely, tertbutyldimethylsilyl derivatives of (S)-5-(hydroxymethyl)-2.5-dihydrofuran-2-ol and (S)-5-(hydroxymethyl)tetrahydrofuran-2-ol. At the first stage of the synthesis, a one-stage modification of the pyranose form of levoglucosenone and cyrene to γ-butanolides was carried out by Bayer-Williger oxidation using H2O2 in the presence of Amberlyst-15 in water. The reduction of unprotected hydroxymethyl-γ-butanolide obtained from cyrene to lactol was studied. The reduction of γ-butanolide by the action of BH3·SMe2, Red-Al, or LiAlH(OtBu)3 in THF at 0° C leads mainly to triol, the product of complete reduction. The desired lactol was obtained using iBu2AlH at -78°C in CH2Cl2 in good yield. Raising the reaction temperature to 0° C led to a decrease in the yield of lactol. It has been established that (S)-5-(hydroxymethyl)-tetrahydrofuran-2-ol exists in both five-membered and six-membered forms. Due to the fact that the target lactols easily undergo a transition from the furanose to the pyranose form, they are not used to produce nucleosides. Therefore, we have studied the approach to the synthesis of stable five- membered lactols. For this purpose, in lactones obtained by the Bayer-Williger reaction, the primary hydroxyl group was blocked using TBSCl. Subsequent reduction of the esters using iBu2AlH gave lactols that existed exclusively in the furanose form. The total yield of the target (S)-5-(hydroxymethyl)-2.5-dihydrofuran-2-ol obtained from levoglucosenone was 39% and (S)-5-(hydroxymethyl)-tetrahydrofuran-2-ol obtained from cyrene was 65%.

Effective Antibiofilm Polyketides against Staphylococcus aureus from the Pyranonaphthoquinone Biosynthetic Pathways of Streptomyces Species

ABSTRACTStreptomycesbacteria are renowned for their ability to produce bioactive secondary metabolites. Recently, synthetic biology has enabled the production of intermediates and shunt products, which may have altered biological activities compared to the end products of the pathways. Here, we have evaluated the potential of recently isolated alnumycins and other closely related pyranonaphthoquinone (PNQ) polyketides againstStaphylococcus aureusbiofilms. The antimicrobial potency of the compounds against planktonic cells and biofilms was determined by redox dye-based viability staining, and the antibiofilm efficacy of the compounds was confirmed by viable counting. A novel antistaphylococcal polyketide, alnumycin D, was identified. Unexpectedly, theC-ribosylated pathway shunt product alnumycin D was more active against planktonic and biofilm cells than the pathway end product alnumycin A, where a ribose unit has been converted into a dioxane moiety. The evaluation of the antibiofilm potential of other alnumycins revealed that the presence of the ribose moiety in pyranose form is essential for high activity against preformed biofilms. Furthermore, the antibiofilm potential of other closely related PNQ polyketides was examined. Based on their previously reported activity against planktonicS. aureuscells, granaticin B, kalafungin, and medermycin were also selected for testing, and among them, granaticin B was found to be the most potent against preformed biofilms. The most active antibiofilm PNQs, alnumycin D and granaticin B, share several structural features that may be important for their antibiofilm activity. They are uncharged, glycosylated, and also contain a similar oxygenation pattern of the lateral naphthoquinone ring. These findings highlight the potential of antibiotic biosynthetic pathways as a source of effective antibiofilm compounds.

Unexpected furanose/pyranose equilibration of N-glycosyl sulfonamides, sulfamides and sulfamates

Arabino N-glycosyl sulfamides, sulfonamides and sulfamates convert from the furanose to the thermodynamically preferred pyranose form in aqueous solution.

α-D-Tagatopyranose

The title compound, C6H12O6, also known as D-Tagatose, occurs in its furanose and pyranose forms in solution, but only the α-pyranose form crystallizes out. In the crystal, the molecules form hydrogen bonded chains propagating in [100] linked by O—H...O interactions. Further O—H...O bonds cross-link the chains.