The synthesis of ethyl trans-cinnamate, by the reaction of benzaldehyde with the stabilized phosphorus ylid (carbethoxymethylene)triphenylphosphorane, serves as a useful experiment to illustrate the Wittig reaction in the introductory organic chemistry laboratory. The reaction is highly stereoselective and affords the product in excellent yield and purity. The stereochemistry of the product is established by examining the coupling constants displayed by the olefinic protons in the 1H NMR spectrum. The experiment highlights several important aspects of organic chemistry such as synthesis, stereochemistry, instrumental analysis, and molecular modeling.

During the investigation of galactitol accumulation in the tissues of galactosemia patients, it was observed that the concentration of free and lipid-bound myo-inositol in the brain was lower than that in normal brain.l.2 At various stages of development, brains from rats fed a diet containing 35% galactose contained somewhat lower concentrations of inositol than did those from comparable control^.^ These findings suggested a possible relationship between galactosemia and myo-inositol metabolism. Because of the possible toxicity of the accumulation of galactitol in brain tissues from galactosemic rats or humans, Dr. Henry J. Wells began a study of the effect of galactitol on the particulate system from rat brain which incorporates inositol into the lipid fraction, as described by Thompson et al.4 The incubating medium consisted of microsomes prepared from brains of young male adult rats of the Holtzman strain; CTP (1.0 mM); MnCl, (2.0 mM); phosphatidic acid (0.125 pmoles) dispersed in Tween-80 (7.5 p g ) ; 2-14C-myoinositol (3.3 x lo8 cpm) ; tris, pH 7.4 (50 mM); potassium phosphate, pH 7.4 (10mM); and galactitol, either omitted or in variable amounts of 0.032-0.25 pmole in a final volume of 0.3 ml.The incubations were carried out at 37" C for two hours.Under the conditions of this assay, it appeared that added galactitol inhibited inositol incorporation into the lipid fraction. However, based on radioactivity measurements, the incorporation of myo-inositol into phosphatidylinositol for control samples was only approximately 0.03%. Further study of this reaction has been carried out, and the results from a number of experiments revealed only mild inhibition ( 10-20% ) when inhibitor concentrations were five times that of substrate; higher concentrations of galactitol did not increase the inhibition. These results suggested that the poor yields of phosphatidylinositol led to the discrepancies observed. We then turned to the method of assay for phosphatidylinositol described by Prottey and Hawthorne5 for the mammalian pancreas enzyme. This assay differed from that of Thompson et al. by utilizing larger amounts of crude microsomes and did not require added phosphatidic acid because of the high endogenous quantities of phosphatidic acid in the microsomal fraction. Albumin was also added in the latter assay procedure although no substantial differences were found when it was omitted. Linear results were obtained when activity (mpmoles phosphatidylinositol produced) was plotted against microsomal protein concentration (0.1-0.8 mg) . Using substrate concentrations in the first order region of the two-step reaction, it was found that galactitol was not inhibitory over a wide range of concentrations. Galactose-1-phosphate and galactose-6-phosphate were likewise not in-*

—At various times during a 2‐day study, the levels of adenine nucleotides and selected glycolytic intermediates were determined in brains of chicks fed a diet containing d‐galactose (40%, w/w). The levels of ATP and glucose 6‐phosphate had decreased by 9 h after initiation of the diet, whereas those of fructose 1,6‐diphosphate, 3‐phosphoglycerate, l‐α‐glycerophosphate, and lactate were not reduced until after 18 h had elasped. Although glucose 1‐phosphate was not appreciably affected, glucose and glycogen were depleted during the latter stages of the toxicity. The cerebral levels of 3′,5′‐cyclic AMP and citrate did not differ significantly between the two dietary groups at 48 h. The changes in the levels of cerebral glycolytic intermediates and high‐energy phosphates during ischemia indicated that the glycolytic rate was diminished in the chicks fed galactose and that high‐energy phosphate compounds were depleted sooner than in controls. After intraperitoneal injection of [14C]glucose, the specific radioactivity and levels of glucose in the plasma from chicks fed either diet were similar, whereas they were significantly reduced in the brains from galactosefed animals. We suggest that galactose interferes with the uptake of glucose into the brain and that this mechanism may be an important factor in d‐galactose‐induced neurotoxicity in the chick.

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was obtained from Eastman Kodak. Calcium chloride was obtained from J. T. Baker Chemical Co. (1313).GC-MS analyses were performed on a Hewlett Packard 5890 gas chromatograph coupled to a 5970 series mass selective detector. The column used was a Supelco 2-4026 15-m × 0.25-mm capillary column packed with SPBM-1 (0.25 µm). GC conditions were as follows: injector and detector temp = 200 °C; oven conditions: initial temp = 70 °C; initial time = 1 min, rate = 15°/min, final temp = 200 °C, final time = 1 min. The total time for each run was 10.67 min. ProcedureThe Grignard Reaction: Preparation of 2-Methyl-1-phenylcyclopentanol As with any Grignard reaction, care should be taken to assure the use of dry glassware and solvent. A magnetic stir bar, 0.47 g of magnesium turnings, and 15 mL of anhydrous ether are placed in a 100-mL, two-necked roundbottom flask fitted with a reflux condenser and an addition funnel containing 2.0 mL of bromobenzene and 5.0 mL of anhydrous ether. A drying tube filled with calcium chloride is connected to the top of the reflux condenser. The bromobenzene solution is then added dropwise at a rate of 1 drop per second with stirring. The appearance of a cloudy reaction mixture signals the initial reaction of magnesium with the halide. The reaction is refluxed after all the bromobenzene has been added. During this time, a solution of 2.0 mL of 2-methylcyclopentanone in 10 mL of anhydrous ether is placed in the addition funnel. After refluxing for 30 min, the heat source is removed and the ketone solution is added dropwise at a rate of 1 drop per second to the Grignard. The heat given off allows the reaction to continue refluxing on its own and a green solution results. After all the ketone solution is added, the heat source is used to continue the reflux for an additional 15 min. The mixture is then cooled in a warm water bath; additional cooling in an ice bath follows. An ether/ethanol solution is made by mixing 1.5 mL of ethanol and 10 mL of ether. While the reaction mixture is still in the ice bath, the ether/ethanol solution is placed in the addition funnel and added slowly (ca. 1 drop per second) to the reaction mixture. This causes formation of a precipitate of magnesium salts. The resulting solution is greenish yellow. Next, 20 mL of a 1 M sulfuric acid solution is placed in the addition funnel and added dropwise to the reaction mixture (still in the ice bath) to dissolve the magnesium salts. The stir bar is removed, and the contents of the flask Figure 1. Formation of the kinetically and thermodynamically favored alkenes 3 and 4 from 1. 1 2 3 4The concept of kinetic versus thermodynamic control is a common theme in organic chemistry. In the introductory organic chemistry classroom, it is often used to explain the products obtained in dehydration reactions, additions to conjugated olefins, and enolate formation. However, while the concept is firmly entrenched in the lecture curriculum, applications of kinetic versus thermodynamic control in the laboratory are less common (1-3)-though such e...

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