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Purpose: To determine the physical compatibility of 10% calcium chloride and 10% calcium gluconate in combination with injectable solutions, administered in the paediatric and adult intensive care unit setting during toxicological resuscitation involving calcium channel blockers and beta-blockers., Methods: Forty-eight combinations were prepared at room temperature, including the following products: calcium chloride, calcium gluconate, insulin, epinephrine, norepinephrine, highly concentrated dextrose solution, sodium chloride, Plasma-Lyte A and Ringer's lactate. A visual evaluation at times 0, 1, 4, 24, 48 and 72 hours and a particle count test with the LS-20 particle counter at times 0, 4, 24 and 72 hours were performed. The admixtures were considered incompatible if there was a precipitate, a colour change, turbidity, viscosity or a gas formation. The stability of calcium salts was also tested in empty IV bags and syringes by the particle count test., Results: All drug mixtures were found to be compatible by visual evaluation and using the particle counter based on United States Pharmacopoeia chapter 788 (USP<788>) specifications. Calcium salts were compatible with insulin and vasopressors in the tested combinations. The stability of 10% calcium salts in empty IV bags and polypropylene syringes was demonstrated for up to 48 hours at room temperature., Conclusion: All the combinations tested were physically compatible for up to 72 hours at room temperature. Clinical use of calcium salt infusions, at an undiluted concentration, in combination with these injectable solutions in a toxicological resuscitation context is considered clinically acceptable., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aluminum and silicon are contaminants found in formulations used to prepare parenteral nutrition. Both elements are leached from glass containers, mainly during the heating cycle for sterilization. Insoluble and biologically inactive species of hydroxyaluminosilicates have been shown to form in solutions containing Al and Si. Therefore, this interaction may play an important role in protecting the body against Al toxicity. In this study, the bioavailability of Al in the presence of Si, calcium gluconate (Gluc.), and potassium phosphate (Phosf.) was investigated in rats. The rats were divided into 10 groups of 5 animals each: control, Al, Si, Al + Si, Gluc, Gluc + Al, Gluc + Al + Si, Phosf, Phosf + Al, and Phosf + Al + Si. The doses, consisting of 0.5 mg/kg/day Al and 2 mg/kg/day Si in the presence or absence of Gluc. or Phosf., were intraperitoneally administered for 3 months. Tissues were analyzed for Al and Si content. Al accumulated in the liver, kidneys, and bones, and the simultaneous administration of Si decreased Al accumulation in these tissues. The presence of Si reduced the amount of Al present by 72% in the liver, by 45% in the kidneys, and by 16% in bone. This effect was lees pronounced in the presence of parenteral nutrition compounds though. Si tissue accumulation was also observed, mainly when administered together with phosphate. These results suggest that Si may act as a protector against Al toxicity, by either reducing Al absorption or increasing its excretion, probably through hydroxyaluminosilicates formation. The presence of calcium gluconate and potassium phosphate decreases or inhibits this effect., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Parenteral nutrition(PN) solutions containing calcium gluconate and cysteine have elevated particle counts when analyzed using laser light obscuration (LO) as recommended by the United States Pharmacopeia. It is unclear whether increased particle formation in these solutions results in decreased availability of cysteine to neonatal patients due to filtration., Objective: The purpose of this study was to measure cysteine concentrations in neonatal PN solutions before and after filtration as well as analyze precipitates on filters., Methods: Solutions of PN containing amino acids with and without cysteine that were compounded with calcium chloride or calcium gluconate plus potassium phosphate were analyzed using LO. Concentrations of cysteine were measured before and after filtration. The effect on particle formation of magnesium sulfate (MgSO 4 ) and D70 was also evaluated., Results: Multiple additives including the specific calcium or D70 additive, cysteine, and MgSO 4 influenced particle formation of particles detected using LO. There was no significant decrease in cysteine concentration because of filtering and there was no difference in the amount of calcium on filters of various solutions after filtration regardless of LO particle counts. Scanning electron micrographic (SEM) analysis found no significant differences in crystal composition. Light microscopic and SEM examination did not show evidence of high particle counts on filters., Conclusion: The increased particle counts detected in neonatal PN solutions containing cysteine added at the time of compounding does not appear to result in increased precipitate or crystal formation. It is not associated witha decrease in cysteine delivery to patients., (© 2021 American Society for Parenteral and Enteral Nutrition.)

The sickle cell disease (SCD) has a genetic cause, characterized by a replacement of glutamic acid to valine in the β-chain of hemoglobin. The disease has no effective treatment so far, and patients suffer a range from acute to chronic complications that include chronic hemolytic anemia, vaso-occlusive ischemia, pain, acute thoracic syndrome, cerebrovascular accident, nephropathy, osteonecrosis and reduced lifetime. The oxidation in certain regions of the hemoglobin favors the reactive oxygen species (ROS) formation, which is the cause of many clinical manifestations. Antioxidants have been studied to reduce the hemoglobin ROS levels, and in this sense, we have searched for new antioxidants glucal-based triazoles compounds with anti-sickling activity. Thirty analogues were synthetized and tested in in vitro antioxidant assays. Two of them were selected based in their effects and concentration-response activity and conducted to in cell assays. Both molecules did not cause any hemolysis and could reduce the red blood cell damage caused by hydrogen peroxide, in a model of oxidative stress induction that mimics the SCD. Moreover, one molecule (termed 11m), besides reducing the hemolysis, was able to prevent the cell damage caused by the hydrogen peroxide. Later on, by in silico pharmacokinetics analysis, we could see that 11m has appropriated proprieties for druggability and the probable mechanism of action is the binding to Peroxiredoxin-5, an antioxidant enzyme that reduces the hydrogen peroxide levels, verified after molecular docking assays. Thus, starting from 30 glucal-based triazoles molecules in a structure-activity relationship, we could select one with antioxidant proprieties that could act on RBC to reduce the oxidative stress, being useful for the treatment of SCD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The fluoride ions of the industrially largely irreplaceable, locally corrosive hydrofluoric acid (HF) can scavenge cations in biological tissues, which explains their high toxic potential, and also leads to local acidification through proton release. The influence of three complexing agents, calcium (Ca 2+ ) gluconate (as 2.5% Ca 2+ gel and individually (2.84%) or commercially (10%) formulated Ca 2+ solution), magnesium (Mg 2+ ) gluconate (2.84%) solution and aluminium (Al 3+ ) solution (Hexafluorine®, pure and diluted) on the absorption of fluoride following HF exposure (1-3 min, 100 μl, 30%/0.64 cm 2 ) through human skin was investigated in an ex-vivo diffusion cell model. Fluoride absorption was assessed over 6-24 h and analysed with a fluoride electrode. Decreasing the contamination time reduced the fluoride absorption distinctly which was further reduced by the application of fluoride-binding decontamination agents (Ca 2+ , Mg 2+ , Al 3+ ) or water alone without being significantly different. Ca 2+ appeared slightly more effective than Mg 2+ in reducing fluoride absorption. Moreover, the addition of pH adjusting buffer promoted the decontamination efficacy. Fluoride-binding agents can facilitate the decontamination of dermal HF exposure. However, prompt decontamination appeared to be the key to successful limitation of fluoride absorption and pushes the choice of decontamination agent almost into the background., (Copyright © 2020. Published by Elsevier Ltd.)

Calcium is a dynamic mineral. Recent discoveries designate that low intake of calcium generates deficiencies and path to other diseases. Food fortification could play a key role to overcome this problem. To cope with this deficiency problem, jellies were formulated with food-grade calcium salts and chicken eggshell powder. In the present study, three different concentrations of calcium salts, as well as eggshell powder were used to formulate jellies. The results of the sensory evaluation indicated that the two jelly products (A&D) in the current study were suitable for consumers. Results of Atomic Absorption Spectrophotometer revealed Jelly A and jelly D had 151±0.05 ppm and 133±0.06 ppm calcium concentration, respectively. Proximate analysis of Jelly A showed that it has 6.0±0.01% ash, 9.2±0.1% moisture, 0.4±0.01 g crude protein, 82.79±0.001 g crude fiber, and 0.61±0.001 g crude fat, while the jelly D that was made with chicken eggshell powder exhibited 6.0±0.01% ash, 10.1±0.1% moisture, 0.5±0.01 g protein, 84.54±0.01 g crude fiber and 1.61±0.01 g crude fat. Therefore, these two jelly A & D were greatly appreciated among other attributes. In spite of naturally available calcium-rich sources, calcium-fortified jellies can be consumed by individuals who are incapable to take sufficient calcium from their diet.

A diversity-oriented synthesis strategy to produce three types of structurally drug-like N-heterocyclic-fused rings has been developed from abundant biomass-derived d-glucal, aniline and water in a stereoselective manner. The overall transformation which entails a cascade of Ferrier reaction and 4π conrotatory imino-Nazarov cyclization was performed in one-pot allowing convenient preparation of scaffolds of high molecular complexity from relatively simple starting materials. While indoline-fused products were readily accessible using ortho-unsubstituted secondary anilines as substrates, reactions with ortho-hydroxyl-anilines furnished fused 1,4-benzoxazines instead. In both cases, InBr 3 acted as the Lewis acid catalyst. By altering InBr 3 to Ln(OTf) 3 , the indoline-fused products could be further converted into tetrahydroquinoline-fused cyclopentenones via ensuing retro-ene rearrangement., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Parenteral nutrition (PN) solutions containing calcium gluconate (CaGlu) and cysteine have elevated particle counts when analyzed using laser light obscuration (LO) as recommended by the United States Pharmacopeia (USP). There are no compatibility studies for solutions compounded with cysteine and containing calcium chloride (CaCl 2 ) using LO. The purpose of this study was to conduct compatibility testing for neonatal PN solutions containing CaCl 2 and CaGlu with cysteine., Methods: Solutions of amino acids (2.5%), containing either CaCl 2 or CaGlu plus potassium phosphate, were compounded with 50 and 100 mg/dL cysteine. Solutions were analyzed for particle counts using LO. Maximum concentrations tested were 20 mmol/L calcium and 15 mmol/L phosphate. Three solutions containing CaCl 2 (144 total solutions) and 2 containing CaGlu (96 total solutions) and the same concentration of additives were compounded. If the average particle count of replicates exceeded USP guidelines, the solution was incompatible., Results: All solutions containing CaGlu had particle counts that exceeded USP guidelines for particle counts ≥10 μm (range, 86-580 particles/mL). For CaCl 2 , 90 of 144 solutions were compatible (range of particle counts for all solutions, 3-121 particles/mL). Maximum compatible concentrations of CaCl 2 and potassium phosphate were 15 mmol/L and 12.5 mmol/L, respectively, for solutions containing both 50 and 100 mg/dL cysteine., Conclusion: This study found that neonatal PN solutions containing CaGlu with added cysteine have significantly higher particle counts, exceeding USP guidelines for compatibility, than those containing CaCl 2 ., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Calcium gluconate glucoheptonate (GGCa) is known to interact with glass containers, leading to the leaching of aluminum from the glass into the solution at toxic level. Therefore, plastic containers seem to be a preferable packaging alternative. Nevertheless, plastics contain potentially toxic additives which could be released into the solution. In order to study content container interaction between GGCa and two plastic containers (polypropylene PP and polyethylene PE containers), an HPLC-PDA method was developed to separate, detect and quantify eleven additives commonly found in plastic materials, with good limit of detection and quantification. This method was then applied to evaluate the compatibility between GGCa and the two plastic containers. After 3 months of storage at 25 °C, none of the eleven additives were detected in GGCa solutions. The safety concern threshold (SCT) and of the analytical evaluation threshold (AET) were evaluated to discriminate the need to identify and qualify unknown peaks., (Copyright © 2018. Published by Elsevier B.V.)

This study investigated the effects of heating skim milk with soluble calcium salts, calcium chloride, calcium lactate, calcium gluconate and calcium lactobionate, on the physico-chemical and rheological properties of milk. Regardless of the type of salt added, the amount of casein in milk serum decreased and the amount of calcium in centrifuge sediment increased along with the serum calcium. The amount of calcium salt required for gelation and the gel firmness (G') varied depending on the salt. The a Ca 2+ order in milk was calcium chloride>calcium lactate>calcium gluconate>calcium lactobionate. With the same amount of added calcium salt, the final G' of milk gel followed the same order. The findings from this study suggest that the different association constants and formation of an intermediate calcium complex with hydroxycarboylate groups affected the calcium ion activity, which may influence the gelation properties in milk., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Calcium chloride (CaCl 2 ) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives., Methods: Samples of solutions compounded with CaCl 2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis., Results: Solutions containing CaCl 2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 ± 23 mcg/L and 126 ± 5 mcg/L. The Al concentration equalled 2730 ± 20 mcg/L for the CaGlu-Gl additive and 310 ± 80 mcg/L for the CaGlu-Pl additive., Conclusion: The study indicates that solutions containing CaCl 2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d., (© 2017 by The American Society for Parenteral and Enteral Nutrition.)

Introduction: Calcium chloride (CaCl 2 ) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives., Methods: Samples of solutions compounded with CaCl 2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis., Results: Solutions containing CaCl 2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 ± 23 mcg/L and 126 ± 5 mcg/L. The Al concentration equalled 2730 ± 20 mcg/L for the CaGlu-Gl additive and 310 ± 80 mcg/L for the CaGlu-Pl additive., Conclusion: The study indicates that solutions containing CaCl 2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d.

Calcium chloride (CC) is the most common cross-linker for the encapsulation of biocontrol microorganisms in alginate beads. The aim of this study was to evaluate if calcium gluconate (CG) can replace CC as cross-linker and at the same time improve viability after drying and rehydration, hygroscopic properties, shelf life and nutrient supply. Hence, the biocontrol fungi Metarhizium brunneum and Saccharomyces cerevisiae were encapsulated in Ca-alginate beads supplemented with starch. Beads were dried and maximum survival was found in beads cross-linked with CG. Beads prepared with CG showed lower hygroscopic properties, but a higher shelf life for encapsulated fungi. Moreover, we demonstrated that gluconate has a nutritive effect on encapsulated fungi, leading to increased mycelium growth of M. brunneum and to enhanced CO 2 release from beads containing Saccharomyces cerevisiae. The application of CG as cross-linker will pave the way towards increasing drying survival and shelf life of various, especially drying-sensitive microbes.

Background: Aluminum contamination of parenteral nutrition solutions has been documented for 3 decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration in the past 3 decades has averaged approximately 4000 μg/L, compared with <200 μg/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity., Methods: Aluminum was quantified in samples collected periodically for more than 2 years from 3 calcium gluconate sources used to prepare parenteral nutrition solutions; 2 packaged in glass (from France and the United States) and 1 in plastic (from Germany); in a recently released plastic-packaged solution (from the United States); and in the 2 glass containers. Phthalate concentration was determined in selected samples of each product and leachate of the plastic containers., Results: The initial aluminum concentration was approximately 5000 μg/L in the 2 glass-packaged products and approximately 20 μg/L in the plastic-packaged product, and increased approximately 30%, 50%, and 100% in 2 years, respectively. The aluminum concentration in a recently released Calcium Gluconate Injection USP was approximately 320 μg/L. Phthalates were not detected in any calcium gluconate solutions or leachates., Conclusions: Plastic packaging greatly reduces the contribution of aluminum to parenteral nutrition solutions from calcium gluconate compared with the glass-packaged product.

Purpose: The purpose of this study was to determine if the addition of calcium gluconate to gellan solution results in a stronger gel structure on initial exposure to tear fluid due to the displacement of calcium from the gluconate ion by tear monovalent cations (Na + , K + )., Methods: Test solutions of gellan and gellan-calcium gluconate were mixed thoroughly with simulated tear fluid (STF) at a 5:1 ratio. The resulting gel was measured for viscosity at 32°C-36°C., Results: The addition of optimized amounts of calcium gluconate to gellan formulations resulted in gellan-calcium gluconate-STF gels of higher strength (statistically significant) than when gellan alone was mixed with STF. Gellan experimental preparations demonstrated thixotropic behavior both before and after addition of STF., Conclusions: It appears possible to enhance the initial in situ gel-forming properties of gellan by adding a divalent cation bound to an ion exchange molecule or resin. Optimal amounts of polyvinylpyrrolidone (PVP) appear to be effective in slowing timolol release when added to gellan and calcium gluconate solutions.

Background: Aluminum contamination from intravenous solutions still represents an unsolved clinical and biochemical problem. Increased aluminum intake constitutes a risk factor for the development to metabolic bone disease, anemia, cholestasis, and neurocognitive alterations. Low-birth-weight preterm infants (LBWPIs) are one of the most exposed populations for aluminum toxicity., Methods: To determine the presence of aluminum in components employed in the preparation of parenteral nutrition (PN) admixtures in Mexico and compare with the maximal aluminum recommended intake from the Food and Drug Administration., Results: Cysteine, trace elements, levocarnitine, phosphate, and calcium salts tested positive for aluminum contamination. All components analyzed were contained in glass vials. Total aluminum intake for 2 sample PN admixtures were calculated in basis to cover nutrition requirements of 2 hypothetical LBWPIs. Aluminum contents, stratified in micrograms per kilogram of weight, exceeded maximal aluminum recommendations, particularly for the very LBWPIs. Substituting sodium phosphate for potassium phosphate salts reduced aluminum intake by 52.7%. Calcium gluconate was the leading aluminum contamination source and confers the greatest risk for aluminum overdose, even with the salt substitution of potassium phosphate by sodium phosphate salts. Adding cysteine and trace elements might increase aluminum content in PN admixtures., Conclusion: Cysteine, trace elements, phosphate, and gluconate salts are the main sources of aluminum in PN prepared in Mexico. Substituting sodium phosphate for potassium phosphate salts reduces aluminum intake but does not resolve aluminum contamination risk. Mineral salts contained in plastic vials should be explored as an additional measure to reduce aluminum contamination., (© 2014 American Society for Parenteral and Enteral Nutrition.)

With the aim of establishing the formulation of a new hydrophilic auto-gelling medical device for biomedical applications, fibroin-based microspheres were prepared. The proposed microspheres were produced by a cost-effective and industrially scalable technique, such as the spray-drying. Spray-dried silk fibroin microspheres were obtained and the effects of different hydrophilic polymer on the process yield, microsphere morphology and conformation transition of fibroin were evaluated. The final auto-gelling formulations were obtained by adding calcium gluconate (as a calcium source for alginate crosslinking) to the prepared microspheres and tested by an in vitro gelling test. This study showed that the combination of fibroin with sodium alginate and poloxamer produced the most promising auto-gelling formulation for specific biomedical applications, such as the treatment of pressure ulcers.

Objectives: To determine whether time to prepare IV medications for hyperkalemia varied by 1) drug, 2) patient weight, 3) calcium salt, and 4) whether these data support the Advanced Cardiac Life Support recommended sequence., Design: Prospective randomized simulation-based study., Setting: Single pediatric tertiary medical referral center., Subjects: Pediatric nurses and adult or pediatric pharmacists., Interventions: Subjects were randomized to prepare medication doses for one of four medication sequences and stratified by one of three weight categories representative of a neonate/infant, child, or adult-sized adolescent: 4, 20, and 50 kg. Using provided supplies and dosing references, subjects prepared doses of calcium chloride, calcium gluconate, sodium bicarbonate, and regular insulin with dextrose. Because insulin and dextrose are traditionally prepared and delivered together, they were analyzed as one drug. Subjects preparing medications were video-recorded for the purpose of extracting timing data., Measurements and Main Results: A total of 12 nurses and 12 pharmacists were enrolled. The median (interquartile range) total preparation time for the three drugs was 9.5 minutes (6.4-13.7 min). Drugs were prepared significantly faster for larger children (50 kg, 6.8 min [5.6-9.1 min] vs 20 kg, 9.5 min [8.6-13.0 min] vs 4 kg, 16.3 min [12.7-18.9 min]; p = 0.001). Insulin with dextrose took significantly longer to prepare than the other medications, and there was no difference between the calcium salts: (sodium bicarbonate, 1.9 [0.8-2.6] vs calcium chloride, 2.1 [1.2-3.1] vs calcium gluconate, 2.4 [2.1-3.0] vs insulin with dextrose, 5.1 min [3.7-7.7 min], respectively; p < 0.001). Forty-two percent of subjects (10/24) made at least one dosing error., Conclusions: Medication preparation for hyperkalemia takes significantly longer for smaller children and preparation of insulin with dextrose takes the longest. This study supports Pediatric Advanced Life Support guidelines to treat hyperkalemia during pediatric cardiac arrest similar to those recommended per Advanced Cardiac Life Support (i.e., first, calcium; second, sodium bicarbonate; and third, insulin with dextrose).

Background: The solubility of inorganic calcium and phosphate in parenteral solutions can be complicated in pediatrics due to the dosing of calcium and phosphorus at the saturation point. The purpose of this study was to test the solubility of sodium glycerophosphate (NaGP) with calcium gluconate in pediatric parenteral nutrition (PN) solutions., Methods: Five PN solutions were compounded by adding calcium gluconate at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L. Each of the 5 solutions was compounded using 1.5% and 4% amino acids, cysteines, and lipids. Compatibility was evaluated by visual inspection (precipitation, haze, and color change). Solutions were evaluated microscopically for any microcrystals and measured by a turbidimeter for changes in turbidity. Solutions were further analyzed using United States Pharmacopeia 788 standards. Six hundred seventy-one PN solutions were compounded at various concentrations and evaluated for visual stability., Results: Compatibility testing showed no changes in the PN solution in any of the concentrations tested. Microscopically, no microcrystals were detected. The turbidimeter measurements had changes of ≤ 0.14 nephelometric turbidity units for all test solutions. There were no visual changes in any of the 671 PN solutions., Conclusion: It is recommended that NaGP replace sodium phosphate in PN solutions. This would eliminate the concern of calcium and phosphorus precipitation and the need of any saturation curves., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Treatment of gem-dihalo-1,2-cyclopropanated d-oxyglycal with primary, secondary, and unsaturated alcohols, in the presence of AgOAc, leads to the formation of chloro-oxepines exclusively. Reaction of the resulting 2-chloro-oxepines with excess alcohol in the presence of AgOAc, do not promote further reactions. This result is in contrast to the reactions of d-glucal derived halo-oxepine with alcohols known previously that lead to the formation of furanoses as the major product under similar reaction conditions. Observation of this study consolidates the reactivity differences of gem-dihalo-1,2-cyclopropanated oxyglycals, as compared to gem-dihalo-1,2-cyclopropanated glycals., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A series of glucal-conjugated sterols as novel vascular leakage blocker were identified through design, synthesis and biologically evaluation. In addition, the structure-activity relationship (SAR) of the glucal-conjugated sterols focusing on the C17-side chain was also established. The sterol analogs linked with the rigid C17-side chain side chains exhibited potent cell survival activities. In particular, analog 21l, which possesses a cyclopentyl oxime moiety, was shown to have excellent pharmacological effects on retinal vascular leakage in a diabetic mouse model., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Continuing dissolution of solid calcium L-lactate pentahydrate in saturated aqueous solutions following addition of solid sodium D-gluconate corresponding to a gluconate/lactate ratio around three was found to result in homogeneous solutions supersaturated with calcium D-gluconate by a factor of seven, from which calcium D-gluconate monohydrate precipitated only slowly. In contrast, dissolution of calcium D-gluconate monohydrate by sodium L-lactate in aqueous solution with the reverse lactate/gluconate ratio also around three did not result in similar homogeneous solutions on the route to solid calcium L-lactate pentahydrate. This increasing supersaturation of calcium D-gluconate during dissolution of calcium L-lactate in aqueous sodium D-gluconate may enhance calcium bioavailability. The dissolution overshooting depends on competitive kinetics and is also of interest in modeling biomineralization and in designing novel food products with increased calcium bioavailability.

Among the calcium hydroxycarboxylates important for cheese quality, D-lactobionate [Ksp = (7.0 ± 0.3) × 10(-3) mol(3) L(-3)] and L-lactate [Ksp = (5.8 ± 0.2) × 10(-3) mol(3) L(-3)] were found more soluble than D-gluconate [Ksp = (7.1 ± 0.2) × 10(-4) mol(3) L(-3)], as indicated by the solubility products determined electrochemically for aqueous 1.0 M NaCl at 25.0 °C. Still, solubility of calcium L-lactate increases by 45% in the presence of 0.50 M sodium D-gluconate and by 37% in the presence of 0.50 M sodium D-lactobionate, while solubility of calcium D-gluconate increases by 66 and 85% in the presence of 0.50 M sodium L-lactate and 0.50 M sodium D-lactobionate, respectively, as determined by complexometric titration. Sodium L-lactate and sodium D-gluconate have only little influence on solubility of calcium D-lactobionate. The increased solubility is described quantitatively by calcium binding to D-gluconate (K1 = 14 ± 3 mol(-1) L) in 1.0 M NaCl at 25 °C, D-lactobionate (K1 = 11 ± 2 mol(-1) L), and L-lactate (K1 = 8 ± 2 mol(-1) L), as indicated by the association constants determined electrochemically. In mixed hydroxycarboxylate solutions, calcium binding is quantitatively described by the geometric mean of the individual association constants for both aqueous 1.0 and 0.20 M NaCl, indicating a 1:1 stoichiometry for complex formation.

Calcium binding kinetic by tissue structures was analysed in 19 health volunteers (13 men and 6 women) of the age group of 33 +/- 6.5 under conditions of acute hypercalcaemia followed by a drip i.v. infusion of calcium gluconate over 2.5 hours. At the end of each 30-minute period the calcium amount retained by tissue structures was recorded and the kinetic parameters of calcium binding were determined according to Langmuir and Scatchard. In all volunteers there was a segment of binding isotherm with positive cooperativity (direct regression in Scatchard) with analogous buffer capacity (beta) for calcium in Langmuir (0.58 +/- 0.24 L kg). One half of volunteers demonstrated cooperativity at [Ca++] 1.3-1.5, while another--at [Ca++] 1.0-1.3 mmol/L which corresponded to the differences in the association constant (Ka) and the number of interactive sites (n) with [Ca++] 1 mmol/L. Additionally, two segments of binding isotherm were detected with the successive binding of calcium to one set of noninteractive sites with similar kinetic parameters of calcium binding (beta, K(a), n). Four different curves of calcium binding in healthy volunteers were established. This study may serve as the basis for a functional diagnostic test of disorders of the tissue calcium-binding properties in different pathological conditions.

Background: The reconstruction of adipose tissue defects is often challenged by the complications that may occur following plastic and reconstructive surgery, including donor-site morbidity, implant migration and foreign body reaction. To overcome these problems, adipose tissue engineering (ATE) using stem cell-based regeneration strategies has been widely explored in the last years. Mounting evidence has shown that adipose-derived stem cells (ADSCs) represent a promising cell source for ATE. In the context of a small number of reports concerning adipose tissue regeneration using three-dimensional (3-D) systems, the present study was designed to evaluate the biological performance of a novel alginate matrix that incorporates human ADSCs (hADSCs)., Results: Culture-expanded cells isolated from the stromal vascular fraction (SVF), corresponding to the third passage which showed the expression of mesenchymal stem cell (MSC) markers, were used in the 3-D culture systems. The latter represented a calcium alginate hydrogel, obtained by the diffusion of calcium gluconate (CGH matrix), and shaped as discoid-thin layer. For comparative purposes, a similar hADSC-laden alginate hydrogel cross-linked with calcium chloride was considered as reference hydrogel (RH matrix). Both hydrogels showed a porous structure under scanning electron microscopy (SEM) and the hADSCs embedded displayed normal spherical morphologies, some of them showing signs of mitosis. More than 85% of the entrapped cells survived throughout the incubation period of 7 days. The percentage of viable cells was significantly higher within CGH matrix at 2 days post-seeding, and approximately similar within both hydrogels after 7 days of culture. Moreover, both alginate-based hydrogels stimulated cell proliferation. The number of hADSC within hydrogels has increased during the incubation period of 7 days and was higher in the case of CGH matrix. Cells grown under adipogenic conditions for 21 days showed that both analyzed 3-D culture systems support adipogenic differentiation in terms of neutral lipid accumulation and perillipin expression. Furthermore, the cells encapsulated in CGH matrix displayed a more differentiated phenotype., Conclusions: The results of this study suggest that both CGH and RH matrices successfully support the survival and adipogenesis of hADSC. An enhancement of biological performance was detected in the case of CGH matrix, suggesting its promising application in ATE.

Dialysis was performed to examine some of the properties of the soluble phase of calcium (Ca) fortified soymilk at high temperatures. Dialysates were obtained while heating soymilk at temperatures of 80 and 100 °C for 1 h and 121 °C for 15 min. It was found that the pH, total Ca, and ionic Ca of dialysates obtained at high temperature were all lower than in their corresponding nonheated Ca-fortified soymilk. Increasing temperature from 80 to 100 °C hardly affected Ca ion concentration ([Ca²⁺]) of dialysate obtained from Ca chloride-fortified soymilk, but it increased [Ca²⁺] in dialysates of Ca gluconate-fortified soymilk and Ca lactate-fortified soymilk fortified with 5 to 6 mM Ca. Dialysates obtained at 100 °C had lower pH than dialysate prepared at 80 °C. Higher Ca additions to soymilk caused a significant (P≤ 0.05) reduction in pH and an increase in [Ca²⁺] of these dialysates. When soymilk was dialyzed at 121 °C, pH, total Ca, and ionic Ca were further reduced. Freezing point depression (FPD) of dialysates increased as temperature increased but were lower than corresponding soymilk samples. This approach provides a means of estimating pH and ionic Ca in soymilks at high temperatures, in order to better understand their combined role on soymilk coagulation., (© 2011 Institute of Food Technologists®)

The purpose of the present study was to examine how the colloid stability features of o/w parenteral nutrition emulsions made with SMOFlipid (lipid emulsion based on soybean oil, medium chain triglycerides, olive oil and fish oil) will change in the presence of high concentration of calcium and glucose if usual micronutrients are also present, according to the needs of the clinical nutrition patient. Particle size analysis, zeta potential, dynamic surface tension measurements and light microscopic screening were carried out to evaluate the possible changes in the kinetic stability of the emulsions. Our results indicate that the higher glucose concentration of 15 or 20% could not compensate the emulsion-destabilizing effect of higher (5 mM) calcium concentration even in the presence of a modern fat emulsion. Therefore calcium demand of undernourished patient requiring 5 mM or higher final Ca²⁺ content in nutrient solution should be supplemented in another way., (Copyright © 2011 Elsevier B.V. All rights reserved.)

By using (N-tosyloxy)-3-O-carbamoyl-D-glucal 10, which removes the need for a hypervalent iodine(III) oxidant, we provide evidence for rhodium nitrenoid-mediated ipso C-H activation as the origin of a C3-oxidized dihydropyranone product 3. This system may be especially susceptible to such a pathway because of the ease of forming a cation upon hydride transfer to the rhodium-complexed acyl nitrene.

A recombinant Zymomonas mobilis strain harboring the plasmid pHW20a-gfo for over-expression of glucose-fructose oxidoreductase (GFOR) was constructed. The specific activity of GFOR enzyme in the new recombinant strain was at least two folds greater than that in the wild strain. The maximum GFOR activity achieved in terms of the volumetric, and the cellular were 2.59 U ml(-1), and 0.70 U mg(-1), respectively, in the batch cultures. A significant improvement of the bioconversion process for the production of sorbitol and gluconic acid from glucose and fructose was made using divalent metal ions which drastically reduced the ethanol yield and significantly increased the yield of target product. Among several divalent metal ions evaluated, Zn(2+) was found to be most effective by inhibiting the Entner-Doudoroff pathway enzymes. The yield of the byproduct ethanol was reduced from 16.7 to 1.8 gl(-1) and the sorbitol yield was increased to almost 100% from 89%. The Ca(2+) enhanced the sorbitol yield and the formation of calcium gluconate salt made the separation of gluconate from the reaction system easier., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Tamiflu is currently the most effective drug for the treatment of influenza, but the insufficient supply and side-effects of this drug demand urgent solutions. We present a practical synthesis of Tamiflu by using novel synthetic routes, cheap reagents, and the abundantly available starting material D-glucal. The strategy features a Claisen rearrangement of hexose to obtain the cyclohexene backbone and introduction of diamino groups through tandem intramolecular aziridination and ring opening. In addition, this synthetic protocol allows late-stage functionalization for the flexible synthesis of Tamiflu analogues. By using the synthesized Tamiflu and its active metabolite (oseltamivir carboxylate), we investigated their influences on neuroendocrine PC12 cells in various aspects. It was discovered that oseltamivir carboxylate significantly inhibits the vesicular exocytosis (regulated secretion) of PC12 cells, and suggests a mechanism underlying the Tamiflu side-effects, in particular its possible adverse influences on neurotransmitter release in the central nervous system., (Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Diltiazem hydrochloride (DTZ) matrix tablets were prepared using polyacrylamide-grafted sodium alginate (PAam-g-SA) co-polymers having different percentages of grafting and their partially hydrolyzed products with a view to achieve sustained release of the highly water-soluble drug. PAam-g-SA co-polymers having different percentages of grafting were synthesized by free radical polymerization using acrylamide (Aam) as monomer and ammonium persulphate (APS) as initiator, and the resulting co-polymers were subjected to alkaline hydrolysis to produce their corresponding partially hydrolyzed co-polymers. Matrix tablets of DTZ were prepared by wet granulation using either PAam-g-SA co-polymers or partially hydrolyzed PAam-g-SA co-polymers. The effect of percentage grafting, drug load and calcium gluconate (CG), used as excipient, was studied in simulated gastrointestinal fluid. While the tablets prepared using the co-polymer having higher percentages of grafting provided faster drug release (100% in 5.5 h), the tablets prepared with the corresponding hydrolyzed co-polymer released the drug slowly (71% in 12 h). This behaviour in release appeared to be controlled by the relative magnitude of the viscosity and the swelling capacity of the copolymers. Moreover, increase in drug load tended to decrease the drug release from all types of tablets and increase in the amount of CG increased the drug release. FT-IR and DSC studies revealed the absence of any interaction between the drug and the co-polymers. The matrix tablet made of partially hydrolyzed graft co-polymer having the highest percentage of grafting provided the most sustained release of the drug.

Background: Precipitation of calcium (Ca) and phosphate (P) salts can lead to potentially lethal outcomes, especially in low-osmolarity parenteral nutrition (LO-PN) formulations. Three concentrations of amino acids (AA) and 2 concentrations of calcium gluconate and sodium phosphate injections on the compatibility of Ca and P in LO-PN admixtures were studied., Methods: Final AA concentrations of 1%, 2%, or 3% (n = 3) and 5% glucose (G) were prepared with either 2.5 or 5 mmol/L (5 or 10 mEq) of Ca (n = 2) and 15 or 30 mmol/L of P (n = 2) for a total of 12 base (3 x 2 x 2) formulations. Triplicate bags of each were analyzed for subvisible micro-precipitates using the light obscuration (or extinction) method for particle counts per milliliter (PC) in the size range of 1.8-50 mum at 7 time intervals over 48 hours stored at 30 degrees C +/- 0.2 degrees C. Visual evaluation was performed using a high-intensity lamp against a black background for detection of macro-precipitates. The pH of all 36 admixtures was measured at 0 and 48 hours. Any precipitated material was isolated and characterized by polarized light microscopy and infrared spectroscopy., Results: Of the 12 base LO-PN formulations tested, those containing 1% and 2% AA with 5 mmol/L of Ca and 30 mmol/L of P showed significant increases in PC, and some resulted in visible dibasic calcium phosphate precipitation. Analyses of variance based on concentrations of AA, Ca, P, and time were highly significant independent variables for increases in the PC of potentially embolic particles, that is, sizes >5 mum (P < .0001). The lowest concentrations of Ca and P, 2.5 and 15 mmol/L, respectively, had significantly lower PC (P < .05) for all sizes compared with the other Ca and P combinations., Conclusions: LO-PN admixtures (AA

A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-D-glucopyranosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy-beta-D-glucopyranose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from D-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.

Introduction: Mineral trioxide aggregate (MTA) fulfills many of the ideal properties of a root end filling material and repair material for furcal perforation. However, its low cohesive property often makes it difficult to handle. To improve the handling properties of MTA root canal filling materials, MTA-like cement was made, and calcium lactate gluconate (CLG) aqueous solution was used to shorten the setting time and enhance the paste viscosity., Methods: CLG solution was prepared by mixing lactic acid, glucono delta lactone, and calcium oxide by wet process. The crystalline property of the CLG powder was characterized by x-ray diffraction. The MTA-like cements were prepared by mixing Portland cement/bismuth oxide/gypsum (75/20/5); ProRoot white MTA (Dentsply Tulsa Dental, Tulsa, OK) was used as a control group. The influence of various liquid phases on initial setting time, handling properties, and pH value were investigated by a Vicat needle, questionnaire of operational hand feel, and pH meter, respectively., Results: By using 23.1 wt% CLG solutions as a liquid phase, the setting time of white MTA was significantly decreased from 155.5 +/- 5.0 to 12.3 +/- 2.5 minutes. The pH values for hydrated white MTA with deionized water and 23.1 wt% CLG solutions were 12.29 +/- 0.02 and 11.81 +/- 0.04 at 72 hours., Conclusions: The results suggest that the addition of amorphous CLG-based liquid phase provides improvement in sealing ability as well as clinical manageability of dental filling materials.

In the Rh(2)(OAc)(4)-catalyzed amidoglycosylation of glucal 3-carbamates, anomeric stereoselectivity and the extent of competing C3-H oxidation depend on the 4O and 6O protecting groups. Acyclic protection permits high alpha-anomer selectivity with further improvement in less polar solvents, while electron-withdrawing protecting groups limit C3-oxidized byproducts. Stereocontrol and bifurcation between alkene insertion and C3-H oxidation reflect an interplay of conformational, stereoelectronic, and inductive factors.

Azoles have a wide spectrum antimycotic activity, but due to some derivatives exhibiting poor water solubility their parenteral administration is limited. The influence of solubilizers on the aqueous solubility of the itraconazole, ketoconazole and miconazole was investigated in order to enhance their solubility for a possible parenteral dosage form. The solubilizer effect of acetate, phosphate and gluconate solutions were studied, along with ethanol, glycerol, macrogol 400, propylene glycol and surfactants, such as polysorbate 20, 60, 80 and sodium taurocholeate. The solubilizing effect of these excipients in binary or ternary combinations was also studied. An HPLC method was used for the solubility assay of the azoles. All of the assessed excipients showed considerable solubility enhancement characteristics, moreover the binary and ternary combinations showed synergistic effects solubilizing more miconazole than what they solubilized separately. Ternary combinations were capable of solubilizing more than 30 mg/ml miconazole, and more than 135 mg/ml of ketoconazole, which in both cases is a very substantial increase in solubility compared to their water solubility. The amount of solubilized drugs may well be used therapeutically, and the formulated solvent system can serve as a base for parenteral solutions.

With focus on the steric effects present in the transition states for the [3,3]-sigmatropic rearrangement, the substrate 5 has been designed to improve the overall stereoselectivity of the Ireland-Claisen rearrangement. Experimentally, it has been found that (1) only Z-6 rearranges to 7 at 80 degrees C and (2) E-6 isomerizes to Z-6 at 80 degrees C, thereby allowing the transformation of 5 into 7 in an almost quantitative yield. To illustrate the usefulness of this approach, two additional examples are given.

Premature infants require protein and energy for their growth and an adequate intake of calcium and phosphorus for their bone formation. However, several factors can affect the stability of intravenous lipid emulsions intended to be administered as neonatal total parenteral nutrition. This study evaluated the effect of additives and various concentrations of both calcium gluconate and glucose-1-phosphate on two intravenous lipid emulsions (Clinoleic 20% and Ivelip 20%) when using Primene 10% as source of amino acids and simulating clinical conditions (24-h storage at 37 degrees C). Two series of experiments for each lipid emulsion were carried out. One used separate ingredients (water, glucose, or amino acids) with various calcium phosphate concentrations; and the second included total parenteral nutrition admixtures with varied amino acid (1%, 2%, or 3.5%) and glucose (8% or 14%) concentrations. Evaluation was performed by visual and microscopic examination and pH, particle size, and zeta potential measurements. Calcium concentrations were determined before and after filtration by atomic absorption spectroscopy. Samples were stored 24 h at 37 degrees C. Investigations of lipid-nutrient admixtures showed a significant decrease of the pH with Primene and a visual instability when mixing with sterile water alone, while total parenteral nutrition admixtures made of Clinoleic 20% or Ivelip 20% were stable regarding pH, particle sizing, and zeta potential after storage conditions. Samples containing only calcium have their zeta potential charge reduced compared to samples containing both calcium and phosphate. Also, the evaluation of calcium phosphate solubility showed a significant decrease of the calcium concentration after filtration of the samples. Our data indicated that total parenteral nutrition admixtures could contribute to protect the lipid emulsion from its physicochemical degradation and that using organic phosphate with calcium gluconate has a less deleterious effect than using calcium alone with total parenteral nutrition. Also, the use of inline filters remains necessary for good protection from hazards of precipitates during the administration of total parenteral nutrition regimens.

Supersaturation of calcium and phosphate in the bath solution and activation of the metal substrate is essential for effective biomimetic growth of apatite on orthopedic implants. In this work, bioactivation of titanium surface was achieved by electrodeposition of a thin layer of calcium phosphate followed by an alkaline treatment to obtain pure hydroxyapatite crystals. The influence of calcium gluconate in the electrolyte solution was evaluated and optimized. Adhesive strength, thickness, structural, and surface characteristics were evaluated. A highly adhesive and uniform layer of hydroxyapatite was formed on titanium surface when the electrodeposition was carried out with an electrolyte solution-containing calcium gluconate. The electrodeposited hydroxyapatite coatings were subjected for biomimetic growth in Kokubo's simulated body fluid (SBF) and Kokubo's modified SBF containing 1.5 times higher concentration of Ca. Biomimetic growth was also improved by the addition of calcium gluconate in the SBF solution., (2008 Wiley Periodicals, Inc.)

A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF3x OEt2 and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.

Lewis acid mediated one-pot transformation of D-glucal in the presence of nucleophiles leads to the formation of racemic alpha-substituted alpha-hydroxymethyl furfuryl derivatives, versatile synthons for biologically active molecules. Transformations using O-, S-, C-, and N-nucleophiles could be achieved readily under mild and scalable conditions. Indium triflate proved to be the catalyst of choice in terms of conversion and regioselectivity.

Background: Patients' exposure to and potential toxicity from aluminum in parenteral nutrition (PN) formulations is an important concern of healthcare providers., Objective: To determine the potential for aluminum toxicity caused by PN in hospitalized adults who have risk factors of both acute kidney injury and PN., Methods: Adults who required PN and had a serum creatinine (SCr) level at least 1.5 times greater than the admission SCr on the first day of PN were studied in a retrospective fashion. Protein was administered based on whether hemodialysis was being used (0.6-1 g/kg/day without hemodialysis; 1.2-1.5 g/kg/day with hemodialysis). Aluminum exposure was determined for each patient by multiplying the volume of each PN component by its concentration of aluminum. Unpaired t-tests, Fisher's exact test, and analysis of variance were used for statistical analysis. Data are presented as mean +/- SD., Results: Thirty-six patients (aged 50.4 +/- 20.4 y; weight 90.2 +/- 32.8 kg) were studied. Initial serum urea nitrogen and SCr were 47 +/- 23 and 3.3 +/- 1.4 mg/dL, respectively. Twelve patients received hemodialysis. The mean aluminum exposure was 3.8 +/- 2 microg/kg/day in the 36 patients. Of these, 29 had safe calculated aluminum exposure (<5 microg/kg/day) and 7 had high calculated aluminum exposure (>5 microg/kg/day). Patients with safe aluminum exposure had significantly higher SCr levels than did those with high aluminum exposure (3.5 +/- 1.5 vs 2.2 +/- 0.7 mg/dL; p < 0.04). Patients with high aluminum exposure received significantly more aluminum from calcium gluconate compared with those who had safe aluminum exposure (357 +/- 182 vs 250 +/- 56 microg/day; p < 0.02). Limitations of the study include its retrospective design, which resulted in calculated versus direct measurement of aluminum., Conclusions: Using our calculations, we believe that most patients with acute kidney injury who require PN do not receive excessive exposure to aluminum from the PN formulation, despite having 2 risk factors (acute kidney injury, PN) for aluminum toxicity.

The synthesis of a range of analogues of the migrastatin macrolide core has been achieved from tri-O-acetyl-D-glucal in order to facilitate structure-activity studies. Efficient macrolactone formation was achieved in the presence of a reactive olefin, by increasing steric hindrance in the olefin environment. Acyclic analogues of migrastatin, structurally related to dorrigocin A, have also been prepared from D-glucal. The dorrigocin A analogues were prepared using the combination of the cross metathesis of ethyl 6-heptenoate with a glycal derivative and a subsequent allylic rearrangement-alkene isomerisation reaction (Perlin reaction). A synthetic route is thus provided that will enable dorrigocin A analogues to be prepared in parallel to migrastatin analogues in the search for novel anti-cancer and anti-arthritic therapeutics. Biological evaluation of one migrastatin and one dorrigocin A sugar derived analogue show that they inhibit proliferation and serum-induced migration of tumour and synovial cells at higher concentrations than evodiamine. Dorrigocin A analogues displayed similar potency to analogues of the migrastatin core.

The unusual ketene acetal benesudon, which is a bioactive fungal metabolite, was synthesized from d-glucose by a route involving radical cyclization to form the five-membered ring and oxidative decarboxylation to generate the key central double bond. The originally suggested stereochemistry for the quaternary center C(5) must be revised, as both possibilities were prepared and a comparison with an authentic sample was made. The absolute configuration of benesudon is 4S,5R,6S.

Effect of calcium gluconate (CG) content on release of dextromethorphan hydrobromide (DMP), model drug, from capsules containing low and medium viscosity grades of sodium alginate (SA) was investigated in different dissolution media. Matrix erosion of the SA matrix capsules in distilled water and pH 7.4 phosphate buffer was compared. Molecular interaction of SA with calcium ion in surface gel layer of the SA matrix capsules was examined using Fourier transform infrared spectroscopy and differential scanning calorimetry. In distilled water and pH 7.4 phosphate buffer, DMP release rate depended on the viscosity grade of SA, whereas a comparable DMP release rate was found in 0.1N HCl. Incorporation of CG into the SA matrix capsules caused a faster drug release in acidic medium because CG acted as a channeling agent in the hydrated insoluble gel matrix of alginic acid. Interaction of calcium ions with carboxyl groups of SA could be formed in surface gel layer of hydrated matrix capsules in distilled water. This led to a more rigid matrix gel structure that caused a slower drug release and matrix erosion. In contrast, the extent of this interaction in pH 7.4 phosphate buffer was less than that in distilled water because the common ion effect and high concentration of sodium ion retarded the hydration of SA and the binding of calcium ions with carboxyl groups of SA. Thus, a small change in drug release and matrix erosion was observed. This finding suggests that microenvironmental interaction between hydrated SA and calcium ion in distilled water could be created in the formulations prepared using low compression force. Moreover, incorporation of CG could moderate drug release and matrix erosion of the SA matrix capsules.

Treatment of 3,4,6-tri-O-acetyl-d-glucal (1) with various aryl amines in the presence of dodecatungstocobaltate under mild and neutral conditions gave sugar derived tetrahydroquinoline derivates.

The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound.

Four derivatives of 2(II)-deoxycellobiose were synthesized from d-glucal and acceptor sugars (d-glucose, d-xylose, d-mannose, and 2-deoxy-d-arabino-hexose) using a cellobiose phosphorylase from Cellvibrio gilvus. The enzyme was found to be an effective catalyst to synthesize the beta-(1-->4) linkage of 2-deoxy-d-arabino-hexopyranoside. The acceptor specificity for the d-glucal reaction was identical to that for the alpha-d-glucose 1-phosphate reaction, but the activity of d-glucal was approximately 500 times less than that of alpha-d-glucose 1-phosphate, using 10mM substrates.