Furylvinylhalogenide. IX. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäureestern mit Aminen

Furylvinylhalides. IX. Reactions of β-fur-2-yl-β-chloro-α-cyanoacrylates with amines β-Fur-2-yl-β-chloro-α-cyanoacrylates 4 react with amines to yield β-Fur-2-yl-β-amino-α-cyanoacrylates 5 . The ¹H-n.m.r. spectra of 5 are discussed.     

Metabolism of sitosteryl β-D-glucoside and its nutritional effects in rats

[4-¹⁴C]Sitosteryl β-D-glucoside, intragastrically administered to rats, was not absorbed by the intestinal mucosa. At three hr after the application, radioactivity was concentrated almost exclusively in the digesta of stomach, small intestine as well as cecum and colon, whereas only low proportions of radioactively labeled compounds were found in the various tissues of the gastrointestinal tract. Minor proportions of labeled metabolites of [4-¹⁴C]sitosteryl β-D-glucoside, such as sitosterol and sitosteryl esters, were formed in the small intestine in vivo and in slices of small intestine in vitro. In the tissues of cecum and colon as well as the digesta derived from them, high proportions of labeled coprositostanol, i.e. 24α-ethyl-5β-cholestan-3β-ol, that obviously had been formed by bacterial degradation of the substrate were detected. The feeding of sitosteryl β-D-glucoside (0.5 g/kg body weight×day) over a period of four weeks did not alter significantly body weights or organ weights of rats. Analyses of steryl lipids of the various organs and tissues confirmed the findings obtained with the radioactive substrate: neither sitosteryl β-D-glucoside nor sitosterol or sitosteryl esters derived therefrom had been transported in appreciable amounts to organs and tissues outside the alimentary canal during the feeding period. Minor proportions of unmetabolized sitosteryl β-D-glucoside were detected in the tissues of stomach and intestine, whereas large proportions of the substrate were found in feces of rats that had received the sitosteryl β-D-glucoside-containing diet; coprositostanol was found in feces of these animals in high proportions as well. Thus, the use of sitosteryl β-D-glucoside as emulsifier or preservative in food and feed does not appear to involve any risk. The systematic nomenclature of the sterols referred to by trivial names is, cholest-5-en-3β-ol (cholesterol); 5α-cholestan-3β-ol (5α-cholestanol); 5β-cholestan-3β-ol (5β-cholestanol, coprostanol); 24α-methylcholest-5-en-3β-ol (campesterol); 24α-methyl-5α-cholestan-3β-ol (5α-campestanol); 24α-methyl-5β-cholestan-3β-ol (5β-campestanol, coprocampestanol); 24α-methyl-cholesta-5,22-dien-3β-ol (brassicasterol); 24α-ethylcholest-5-en-3β-ol (sitosterol, β-sitosterol); 24α-ethyl-5α-cholestan-3β-ol (5α-sitostanol); 24α-ethyl-5β-cholestan-3β-cholestan-3β-ol (5β-sitostanol, coprositostanol); 24α-ethylcholesta-5,22-dien-3β-ol (stigmasterol).     

Furylvinylhalogenide. X [1]. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäurederivaten mit Hydrazinen

Furylvinylhalides. X. Reactions of β-Fur-2-yl-β-chloro-α-cyanoacrylic Acid Derivatives with Hydrazines β-Fur-2-yl-β-chloro-α-cyanoacrylic acid derivatives 3 react with hydrazines yielding 3-fur-2-yl-5-aminopyrazoles 5 or 3-fur-2-yl-4-cyanpyrazolin-5-ones 6 . In some cases the β-hydrazino-α-cyanoacrylic acid derivatives 4 , could be isolated.     

New Intermediates and Dyes for Synthetic-polymer Fibres Derivatives of 2-Chloro-4-nitro-4‘-(N-β-hydroxyethyl-N- β-cyanoethylamino)azobenzene

Condensation of 2-chloro-4-nitro-4^t-(N-(β-hydroxyethyl-N-β-cy anoethylamino)azobenzene with various acid chlorides, chloroformates, isocyanates, isothiocyanates and reactive halogeno compounds gives dyes of excellent fastness to light and sublimation on polyester fibres.     

Disterylether – Artefakte der Fettbleichung

Disteryl Ethers – Artifacts of Bleaching of Fats and Oils (1) Disteryl ethers are formed by acid catalyzed dehydration of Δ⁵-unsaturated sterols during the bleaching of fats and oils with acid-activated bleaching earths. These artifactual lipids can be used as markers of the bleaching process. Distanyl ethers can be produced by catalytic hydrogenation of Δ^5,5'-unsaturated disteryl ethers. (2) Spectroscopic characterization of disteryl ethers and distanyl ethers showed that these steroidal lipids are highly symmetrical compounds with the oxygen atom of the ether linkage in the center of symmetry. Conformation of C-O bonds at the ether bridge is 3β/3'β showing that both types of compounds are periplanar and voluminous molecules. (3) Mixtures of disteroid ethers are separated by silver ion HPLC into the unsaturated disteryl ethers and the saturated distanyl ethers. Individual components of these two classes of disteroid ethers are separated by capillary GLC. Determination of individual compounds may be a conclusive proof of bleaching and hydrogenation of fats and oils. (4) Di[4,4'-¹⁴ C]cholesteryl ether and di [4,4'-¹⁴C]sitosteryl ether, intragastrically administered to mice, were found to be neither absorbed nor metabolized in the gastrointestinal tract. Both dicholesteryl ether and disitosteryl ether, fed to mice at a level of 400 mg/kg body weight x day for 4 weeks, did not lead to ill effects in the animals.     

Absorption and metabolism of 1-14C-hydroxy octadecadienoate in the rat

The metabolism of 1-¹⁴C-9(13)-hydroxy octadecadienoic acid methyl ester (1-¹⁴C-HAME) by the rat was investigated in vivo and in liver slices. A 1.5 mg dose of 1-¹⁴C-HAME administered by stomach tube was efficiently hydrolyzed and absorbed from the intestinal tract. In comparison with 1-¹⁴C-methyl linoleate (1-¹⁴C-ML), 1-¹⁴C-HMAE was more extensively oxidized to¹⁴CO₂ in vivo and in vitro. After 1-¹⁴C-HAME administration as much as 50% of the radioactivity in the adipose tissue triglycerides was associated with¹⁴C-hydroxy fatty acids. The remaining activity was present in randomly labeled normal fatty acids. No evidence was obtained for the incorporation of¹⁴C-hydroxy acids into liver lipids; most of the radioactivity from 1-¹⁴C-HAME in this organ was recovered in saturated and monoenoic fatty acids. About 10% of the radioactivity 24 hr after 1-¹⁴C-HAME administration was associated with triglyceride trienoic acids, indicating that at least a portion of this acid was dehydrated in the liver. An unidentified polar acid was detected in the urine of the 1-¹⁴C-HAME-treated animals.     

Studies on the in vivo metabolism of retinoic acid in the rat

A time study of the metabolism of 6,7-¹⁴C-retinoic acid after intraperitoneal injection of physiological levels (17 μg, 0.39 μc) into vitamin A deficient rats, which had been repleted with retinoic acid for two weeks up to two days before injection, resulted in a rapid metabolism to more polar compounds in the small intestine and its contents and a slower metabolism to primarily different materials in the liver and kidney. The major route of metabolism resulted in the urinary excretion of 60% of the injected dose in 24 to 27 hr. Urinary metabolites of 15-¹⁴C-retinoic acid were eluted from silicic acid at a similar concentration of solvents as the ring labeled metabolites although only 32% of the injected dose was recovered in 24 hr. Compounds chromatographically similar to the urinary metabolites were observed at various times in the liver, kidney and small intestine plus contents in addition to retinoic acid and other metabolites. The relative amounts of the metabolites in the different tissues studied varied as a function of the tissue and the time of analysis after injection. Most of the radioactivity from all tissues was extractable into methanol. A liver subcellular distribution of the radioactivity derived from the intraperitoneal injection of 650 μg of 6,7-¹⁴C-retinoic acid (25.9 μc) after 3 hr indicated a minimal level of association of radioactivity (150–250 dpm/mg protein) with all fractions and a greater association of radioactivity with the lysosomal-microsomal fraction (300–350 dpm/mg protein) and the 60–100% ammonium sulfate precipitable (750–800 dpm/mg protein) and 100% ammonium sulfate soluble fractions (422 dpm/mg protein) of the soluble supernatant.     

r-5-(α-Halogenbenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-one als Ringtautomere von α-(Arylaminocarbonyloxy)-β-halogen-dihydrochalkonen

r-5-(α-Halogenobenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-ones as Ring Tautomers of α-(N-Arylaminocarbonyloxy)-β-halogeno-dihydrochalcones The reaction of chalcone halogenohydrins ( 1–3 ) with arylisocyanates does not stop at the stage of the α-arylaminocarbonyloxy-β-halogeno-dihydrochalcones ( 7 ), but the cyclic urethanes 4–6 are formed. Compound 7h was synthesized independently. The structure and stereochemistry of 4–6 and 7h were determined by ¹³C n.m.r. spectroscopy.     

Metabolism of gossypol,biosynthesized from methyl-14C-and carboxyl-14C-labeled sodium acetate,in rat

Stereospecifically labeled radioactive gossypol was biosynthesized by incubating cotton seedlings with either methyl-¹⁴C- or carboxyl-¹⁴C-labeled sodium acetate. The respective products were purified as gossypol acetic acid. Each radioactive gossypol acetic acid preparation was dissolved in oil and administered by stomach tube to two rats. A negligible amount of radioactivity was found in the expired air of the rats receiving the gossypol biosynthesized from 1-¹⁴C-sodium acetate; however, a significant quantity of radioactivity was found in the expired air of rats that received gossypol labeled from 2-¹⁴C-acetate. This indicated that the binaphthalene nucleus of the gossypol molecule was not degraded to CO₂ in the rat. A low level of radioactivity was found in the urine of rats administered either gossypol preparation. In each rat there was radioactivity found in all the tissues that were analyzed; however, the major portion of the radioactivity was excreted in the feces. Paper no. 4189, North Carolina State University Experiment Station, Raleigh, North Carolina. Research described herein represents work done by Charles L. Skutches in partial fulfillment of the requirement for the Ph.D. degree.     

Synthesis and characterization of poly(1-sila-cis-pent-3-enes) substituted with pendant pyridinyl groups

Poly[1-methyl-1-[3′-(3″-pyridinyl)propyl]-1-sila-cis-pent-3-ene], poly[1-phenyl-1-[3′-(3″-pyridinyl)propyl)-1-sila-cis-pent-3-ene], and poly[1-phenyl-1-(4′-pyridinyl)-1-sila-cis-pent-3-ene] were synthesized by the anionic ring-opening polymerization of 1-methyl-1-[3′-(3″-pyridinyl)propyl]-1-silacyclopent-3-ene, 1-phenyl-1-[3′-(3″-pyridinyl)propyl]-1-silacyclopent-3-ene, and 1-phenyl-1-(4′-pyridinyl)-1-silacyclopent-3-ene, respectively. These are the first polycarbosilanes which contain heterocyclic pyridine units as side-chain substituents. These polymers were characterized by¹H,¹³C, and²⁹Si NMR as well as by IR and UV spectroscopy. The molecular weight distributions were determined by gel permeation chromatography, glass transition temperatures, by differential seanning calorimetry: (DSC) and thermal behavior, by thermogravimetric analysis. (TGA).     

13C-NMR-Spektroskopie von bromierten 3-Keto- und 3β-Acetoxy-5α-cholestan-Verbindungen

¹³C-NMR Spectroscopic Investigations of Brominated 3-Keto- and 3β-Acetoxy-5α-cholestane Derivatives The chemical shifts of some brominated 3-keto- and 3β-acetoxy-5α-cholestane derivatives are determined. The substituent effects of bromine atoms on chemical shifts (SCS) and their additive behaviour, especially γ-SCS, are discussed.     

Placental transport oftrans fatty acids in the rat

Placental transport of 9-trans [1-¹⁴C] octadecenoic (elaidic) and 9-trans,12-trans [1-¹⁴C] octadecadienoic (linoelaidic) acids was demonstrated in rats. On the 18th day of gestation, a¹⁴C-labeled albumin complex of elaidic or linoelaidic acid was injected into the jugular vein of pregnant rats. For comparison, 9-cis [1-¹⁴C] octadecenoic (oleic) or 9-cis,12-cis [1-¹⁴C] octadecadienoic (linoleic) acid also was injected into the maternal circulation of rats. All animals were sacrificed 1 hr following injection. Lipid composition and distribution of label were determined in maternal plasma, placental and fetal tissues. Differences in specific activities of plasma, placental and fetal total lipids indicated a decreasing concentration gradient for bothcis andtrans isomers of octadecenoic and octadecadienoic acids. Distribution of radioactivity in various lipid components was determined by thin layer chromatography. Irrespective of the label, the highest percentage of total radioactivity was carried by triglycerides (TG) in maternal plasma (∼60–80%), and was incorporated mainly in phospholipids (PL) of fetal tissues (∼50–60%). A nearly equal distribution of the label was found between PL and TG of placental lipids (∼40%). Radioactivity of fatty acid methyl esters (FAME) determined by radiogas liquid chromatography indicated that after injection of linoelaidate, radioactivity of maternal plasma, placental and fetal tissue FAME was associated only witht,t-18∶2. Following injection of elaidate, all the radioactivity in placental FAME was associated witht-18∶1; however, in fetal tissues, the label was distributed between 16∶0 andt-18∶1. These findings suggest that, in contrast to linoelaidic acid, rat fetal tissues can metabolize elaidic acid via β oxidation to form acetyl CoA and palmitic acid.     

Syntheses and Biological Activities of Polymers Containing 3′-Azido-3′-deoxythymidine

The new monomer, 5′-O-methacryloyl-3′-azido-3′-deoxythymidine (MAZT), was synthesized by the reaction of methacryloyl chloride and 3′-azido-3′-deoxythymidine (AZT). Poly(MAZT) and copolymers of MAZT with vinyl acetate (VAc) and maleic anhydride (MAH) were synthesized by radical polymerizations. The synthesized MAZT and polymers were identified by ¹H nuclear magnetic resonance (NMR), ¹³C NMR, elemental analysis and gel permeation chromatography. The quantities of MAZT units in poly(MAZT-co-VAc) and poly(MAZT-co-MAH) were 45 and 27 mol%, respectively. The weight average molecular weights of the polymers synthesized were in the range from 8800 to 17600. The in vitro cytotoxicities of samples against K562 human leukaemia cell line at 100 μg ml^-1 decreased in the following order: poly(MAZT-co-MAH) > poly(MAZT-co-VAc) > poly(MAZT) > MAZT > AZT. The in vivo anti-tumour activities of the polymers synthesized against Balb/C mice bearing sarcoma 180 tumour cells were greater than those of 5-fluorouracil at all concentrations.     

Formation of diglycerides of long turnover time from labeled acetate and glucose in rat tissues

Rat adipose tissue pieces were incubated with acetate-2-¹⁴C and glucose-¹⁴C(U), respectively, and liver slices with acetate-2-¹⁴C. The labeled tissues were then reincubated in inactive medium, and the changes of radioactivity in the different lipid classes were determined. In all three experiments a significant amount of radioactivity was incorporated in the diglycerides. During 1 hr of reincubation in inactive medium the radioactivity of diglycerides decreased from 35 to 26% of the total lipid activity in the adipose tissue labeled with acetate. In the adipose tissue labeled with glucose radioactivity fell from 25 to 19%. In liver slices 11% of the labeled acetate was incorporated in the diglycerides, and during the 2 hr of reincubation this value fell to its half. The radioactivity of the uniformly labeled glucose was distributed equally in the fatty acids and the glycerol. The distribution of radioactive glycerol between diglycerides and triglycerides was similar to that of the labeled fatty acids. Triglyceride synthesis seems to always be accompanied by the formation of diglycerides with a lastint turnover time.     

Fatty acyl desaturation in isolated hepatocytes from Atlantic salmon (Salmo salar): Stimulation by dietary borage oil containing γ-linolenic acid

The effects of different dietary oils on the fatty acid compositions of liver phospholipids and the desaturation and elongation of [1-¹⁴C]18∶3n−3 and [1-¹⁴C]18∶2n−6 were investigated in isolated hepatocytes from Atlantic salmon. Atlantic salmon smolts were fed diets containing either a standard fish oil (FO) as a control diet, a 1∶1 blend of Southern Hemisphere marine oil and tuna orbital oil (MO/TO), sunflower oil (SO), borage oil (BO), or oliver oil (OO) for 12 wk. The SO and BO diets significantly increased the percentages of 18:2n−6, 18:3n−6, 20:2n−6, 20:3n−6, and total n-6 polyunsaturated fatty acids (PUFA) in salmon liver lipids in comparison with the FO diet. The BO diet also increased the percentage of 20:4n−6. Both the SO and BO diets significantly reduced the percentages of all n−3 PUFA in comparison with the FO diet. The OO diet significantly increased the percentages of 18:1n−9, 18:2n−6, total monoenes, and total n−6 PUFA in liver lipids compared to the FO diet, and the percentages of all n−3 PUFA were significantly reduced. With [1-¹⁴C]18:3n−3, the recovery of radioactivity in the products of Δ6 desaturation was significantly greater in the hepatocytes from salmon fed SO, BO, and OO in comparison with the FO diet. The BO diet also increased the recovery of radioactivity in the products of Δ5 desaturation. Only the BO diet significantly affected the desaturation of [1-¹⁴C]18:2n−6, increasing recovery of radioactivity in both Δ6- and Δ5-desaturation products. In conclusion, dietary BO, enriched in γ-linolenic acid (18:3n−6), significantly increased the proportions of both 20:3n−6 and 20:4n−6 in salmon liver phospholipids and also significantly increased the desaturation of both 18:2n−6 and 18:3n−3 in salmon hepatocytes. The possible relationships between dietary fatty acid composition, tissue phospholipid fatty acid composition, and desaturation/elongation activities are discussed.     

Volume-dependent transfer of free fatty acids from ehrlich ascites carcinoma to host tissues

The recovery of [9.10-³H] palmitate complexed to mouse serum albumin was studied 5 sec after ip injection into mice bearing Ehrlich ascites carcinomas. Only about 55% of the injected radioactivity remained in the tumor cells, tumor extracellular fluid and peritoneal washings in mice having ca. 5 ml of the ascites tumor (cells plus extracellular fluid). However the recoveries were nearly quantitative from tumors of larger volume (≥8 ml). A model is proposed to account for the volume-dependent transfer of palmitate from tumor to host in these cancerous mice. P.M. was the recipient of a fellowship from the Fonds National Suisse de la Recherche Scientifique during this study.     

Steroide. XLVI. Darstellung von 15.16.17-trisubstituierten Steroiden durch Ringöffnung von 17β-substituierten 15β.16β-Epoxy-östra-1.3.5(10)-trien-3-methyläthern

Steroids. XLVI. Preparation of 15,16,17-Trisubstituted Steroids by Ring Cleavage of 17β-Substituted 15β,16β-Epoxy-estra-1,3,5(10)-triene 3-Methylethers The ring cleavage of 15β.16β-epoxy-3-methoxy-estra-1-3,5(10)-triene-17β-ol 1a with strong nucleophiles occurs mainly at C-16, yielding 16α-substituted 15β,17β-diols 2a–f . Besides this, 1a is cleaved to a small extent at C-15, yielding the 15α-substituted 16β,17β-diols 3a—f and the Δ¹⁴-16,17β-diol 5a . The structures have been elucidated by means of i.r., H-n.m.r. and mass spectroscopy.     

Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat

The incorporation of radioactivity from orally administered linoleic acid-1-¹⁴C, linolenic acid-1-¹⁴C, arachidonic acid-³Hg, and docosahexaenoic acid-¹⁴C into the liver and brain lipids of suckling rats was studied. In both tissues, 22 hr after dosing, 2 distinct levels of incorporation were observed: a low uptake (from 18∶2-1-¹⁴C and 18∶3-1-¹⁴C) and a high uptake (from 20∶4-³H₈ and 22∶6-¹⁴C). In adult rats, the incorporation of radioactivity into brain lipids from 18∶2-1-¹⁴C and 20∶4-³H was considerably lower than the incorporation into the brains of the young rats. In the livers of the suckling rats, the activity from the 18 carbon acids was associated mostly with the triglyceride fraction, whereas the activity from the 20∶4-³H₈ and 22∶6-¹⁴C was concentrated in the phospholipid fraction. In the brain lipids, the activity from the different fatty acids was associated predominantly with the phospholipids. In the liver and brain phospholipid fatty acids, some of the activity in the 18∶2-1-¹⁴C and 18∶3-1-¹⁴C experiments was associated with 20 and 22 carbon polyunsaturated fatty acids; however, radioactivity from orally administered 20∶4-³H₈ and 22∶6-¹⁴C was incorporated intact into the tissue phospholipid to a much greater extent compared with the incorporation of radioactivity into 20∶4 and 22∶6 in the experiments where 18∶2-1-¹⁴C and 18∶3-1-¹⁴C, respectively, were administered. Possible reasons for these differences are discussed. Rat milk contains a wide spectrum of polyunsaturated fatty acids, including linoleate, linolenate, arachidonate, and docosahexaenoate. During the suckling period in the rat, there is a rapid deposition of 20∶4 and 22∶6 in the brain. The results of the present experiments suggested that dietary 20∶4 and 22∶6 were important sources of brain 20∶4 and 22∶6 in the developing rat.