Abstract  2,5-Cyclohexadienyl-substituted aryl or vinylic iodides have been reacted with carbon nucleophiles (diethyl malonate and 2-methyl-1,3-cyclohexanedione), nitrogen nucleophiles (morpholine, potassium phthalimide, N-benzyl tosylamide, di-tert-butyl iminodicarboxylate, lithium azide, and anilines), a sulfur nucleophile (sodium benzenesulfinate), and oxygen nucleophiles (lithium acetate and phenols) to afford products of cyclization and subsequent cross-coupling in good to excellent yields. In most cases, this process is highly diastereoselective. The reaction is believed to proceed via (1) oxidative addition of the aryl or vinylic iodide to Pd(0), (2) organopalladium addition to one of the carbon-carbon double bonds, (3) palladium migration along the carbon chain on the same face of the ring to form a pi-allylpalladium intermediate, and (4) nucleophilic displacement of the palladium.

Abstract  Palladium-catalyzed reactions of aryl bromides and chlorides with two common stabilized carbanions-enolates of dialkyl malonates and alkyl cyanoesters-are reported. An exploration of the scope of these reactions was conducted, and the processes were shown to occur in a general fashion. Using P(t-Bu)(3) (1), the pentaphenylferrocenyl ligand (Ph(5)C(5))Fe(C(5)H(4))P(t-Bu)(2) (2), or the adamantyl ligand (1-Ad)P(t-Bu)(2) (3), reactions of electron-poor and electron-rich, sterically hindered and unhindered aryl bromides and chlorides were shown to react with diethyl malonate, di-tert-butyl malonate, diethyl fluoromalonate, ethyl cyanoacetate, and ethyl phenylcyanoacetate. Although alkyl malonates and ethyl alkylcyanoacetates did not react with aryl halides using these catalysts, the same products were formed conveniently in one pot from diethylmalonate by cross-coupling of an aryl halide in the presence of excess base and subsequent alkylation.

Abstract  Azorhizobium caulinodans mutant 62004 carries a null allele of pdhB, encoding the E1beta subunit of pyruvate dehydrogenase, which converts pyruvate to acetyl-CoA. This pdhB mutant completely lacks pyruvate oxidation activities yet grows aerobically on C(4) dicarboxylates (succinate, L-malate) as sole energy source, albeit slowly, and displays pleiotropic growth defects consistent with physiological acetyl-CoA limitation. Temperature-sensitive (ts), conditional-lethal derivatives of the pdhB mutant lack (methyl)malonate semialdehyde dehydrogenase activity, which thus also allows L-malate conversion to acetyl-CoA. The pdhB mutant remains able to fix N(2) in aerobic culture, but is unable to fix N(2) in symbiosis with host Sesbania rostrata plants and cannot grow microaerobically. In culture, A. caulinodans wild-type can use acetate, beta-D-hydroxybutyrate and nicotinate--all direct precursors of acetyl-CoA--as sole C and energy source for aerobic, but not microaerobic growth. Paradoxically, acetyl-CoA is thus a required intermediate for microaerobic oxidative energy transduction while not itself oxidized. Accordingly, A. caulinodans energy transduction under aerobic and microaerobic conditions is qualitatively different.

Abstract  [structures: see text] Enantioselectivities and yields comparable to the best catalysts reported previously can be achieved in the addition of potassium dimethyl malonate to diphenylallyl acetate by the use of Pd(0) complexes of bis-phospholanes prepared from D-mannitol. By appropriate changes in the C2-C5 substituents, rare example of a useful monophosphine can also be prepared by a similar route. In both instances chirality of C3 and C5 oxygen seems to play a crucial role in the asymmetric induction.

Abstract  Carnitine palmitoyltransferases 1 and 2 (CPT-1 and CPT-2) catalyze the transfer of long chain fatty acids between carnitine and coenzyme A. Unlike CPT-2, CPT-1 exists in at least two isoforms with different physical and kinetic properties. Liver and skeletal muscle each contain a different isoform of CPT-1. Cardiac muscle contains both isoforms, and the minor component is identical to the isoform found in the liver. 2-[6-(2,4-Dinitrophenoxy)hexyl]oxiranecarboxylic acid (2) was reported to be a selective inhibitor for the liver isoform of CPT-1. A synthesis of 2 is described here which involves the reaction of diethyl malonate with 1-bromo-6-phenoxyhexane.

Abstract  Excellent yields and at least 95 % ee can be achieved for the addition of dimethyl malonate to cycloalkenyl acetates by using a palladium complex of the new phosphanyldihydrooxazole ligand L as a catalyst (see scheme). The ligand L can be synthesized from commercially available trans 4-hydroxy-L-proline in four steps. BOC=tert-butoxycarbonyl.

Abstract  In most animal species and many prokaryotes, methylmalonyl CoA mutase catalyzes isomerization between methylmalonyl CoA and succinyl CoA using adenosylcobalamin as a cofactor. We describe the absence of this enzyme in Aspergillus nidulans based on the absence of enzyme activity in vitro and the failure to metabolize methylmalonate or grow in media containing this organic acid as the sole carbon source. These data contrast previous assumptions that propionate may be metabolized through propionyl CoA and methylmalonyl CoA to the TCA cycle in this organism. This is consistent with the separate evolution of these pathways in animals and lower eukaryotes due to the distinct endosymbiotic origin of their mitochondria.

Abstract  Non-rhamnose-containing phosphoramidon analogues, in which the amide bond was replaced by the isosteric ketomethylene group, have been synthesized in order to stabilize these compounds to peptidase degradation. The key step in this synthesis was suitable alkylation of a 4-ketodiester, prepared from Z-Leu chloromethyl ketone and dimethyl malonate. The ketomethylene dipeptide derivatives P-Leu psi (COCH2)(RS)Xaa-OMe (Xaa = Trp, Phe) are good inhibitors of thermolysin, ACE and specially enkephalinase.

Abstract  Methylmalonate and propionate, the major metabolites of the propionate pathway of fatty and amino acid metabolism used at 1-4 mM cause selective inhibition of succinate and palmitoyl carnitine oxidation in liver mitochondria. Methylmalonate is more specific towards succinate, whereas propionate--towards palmitoyl carnitine oxidation. Methylmalonate is transported to mitochondria at a high rate with no effect on succinate transport. Being injected intramusculary methylmalonate has no inhibiting effect on the oxidative activity of mitochondria but is able to activate succinate and palmitoyl carnitine oxidation. The inhibiting effect of propionate on palmitoyl carnitine oxidation is a long-term one. Injections of these metabolites precursors, isoleucine, methionine and valine, produce an activating effect on succinate oxidation. Thus, propionate pathway metabolites may participate in the regulation of lipid-carbohydrate metabolism.

Abstract  The synthesis of (6R,5S,2RS)-6-amino-5-hydroxy-2-isobutyl-4-oxo-7- phenylheptanoic acid (9), a carbaanalogue of the aminopeptidase (AP) inhibitor bestatin (1) is described. This synthesis was carried out by a malonic ester alkylation with the suitably protected halomethyl ketone of (2S,3R)-AHPBA*), followed by a second alkylation with isobutyl bromide of the resulting 4-ketodiester, and subsequent decarboxylation and deprotection. The inhibitory potencies of the 1:1 diastereomeric mixture 9 against AP-B, AP-M and Leu-AP were approximately 10-fold lower than those of bestatin.

Abstract  Reaction of 6-chloro,9-(2-acetoxyethoxymethyl)purine 1 with ethyl cynoacetat, malononitrile and diethyl malonate in presence of NaH and DMF yielded the corresponding 6-methylidene derivatives 2a-c, which were deprotected by treatment with methanolic Ammonia to yield 3a-c. During the reaction of 1 with cyanoacetamide deacetylation took place spontaneously resulting in the deprotected acyclic nucleoside 4. Treatment of 2a with methyliodide in presence of NaH and DMF yielded the N-methyl derivative 5. NMR and mass spectra of the synthesized compounds are discussed.

Abstract  The effects of branched-chain amino acid metabolites on granulocyte-macrophage progenitor cell proliferation in marrow culture are reported. Isovalerate and propionate profoundly suppress granulopoiesis at both 3.2 and 6.4 mM concentrations, whereas methylmalonate and other metabolites suppress to a lesser degree. The parent branched-chain amino acids leucine, isoleucine, and valine do not suppress in vitro granulopoiesis at similar concentrations. Because the concentrations of the organic acids tested fall within the pathophysiologic ranges observed in patients with isovaleric, propionic, and methylmalonic acidemias, we suggest that elevated in vivo levels of isovalerate, propionate, and to a lesser degree methylmalonate are responsible for the neutropenia observed in these disorders.

Abstract  A method for the determination of blood oxalate by gas chromatography is described. After clarification of the serum with acetone, the oxalate was extracted, ethylated and analysed on a gas chromatograph. The concentration of oxalate in the sample was determined by comparison with the elution pattern of diethylmalonate used as an internal standard. Using this technique, the recovery of added oxalate was more than 80%. Normal subjects were found to have blood oxalate levels of 27 mumol/l or less.

Abstract  The following compounds do not either replace or spare the growth requirement for Vit. B12 of either E. gracilis or O. malhamensis: DL-β-methyl-aspartate, L-threo-β-methyl-aspartate, ureido-β-methyl-aspartate, N-acetyl-L-threo-β-methyl-aspartate, and methyl-malonate. Inhibition of growth of E. gracilis by benzimidazole is not annulled by β-methyl-aspartate.

Abstract  Leaves and leaf slices from Aloe arborescens Mill. were used to study the interrelations between Crassulacean acid metabolism, photosynthesis, and respiration. Oxygen exchange of leaf slices was measured polarographically. It was found that the photosynthetic utilization of stored malic acid resulted in a net evolution of oxygen. This oxygen production, and the decrease in acid content of the leaf tissue, were completely inhibited by amytal, although the rate of respiratory oxygen uptake was hardly affected by the presence of this inhibitor of mitochondrial electron transport. Other poisons of respiration (cyanide) and of the tricarboxylic acid cycle (trifluoroacetate, 2-diethyl malonate) also were effective in preventing acid-dependent oxygen evolution. It is concluded that the mobilization of stored acids during light-dependent deacidification of the leaves depends on the operation of the tricarboxylic acid cycle and of the electron transport of the mitochondria.A comparison of enzyme activities in extracts from Aloe leaves and from other plants and studies of leaf anatomy and chloroplast morphology revealed typical characteristics of C(3)-, as well as C(4)-, plants in Aloe.

Abstract  Gollakota, K. G. (University of Illinois, Urbana) and H. Orin Halvorson. Biochemical changes occurring during sporulation of Bacillus cereus T. II. Effect of esters of organic acids on sporulation. J. Bacteriol. 85:1386-1393. 1963.-Sporulation of Bacillus cereus T in yeast extract-glucose-minerals medium was specifically inhibited by alpha-picolinic acid (APA), if the acid was added before the pH of the culture began to rise. The effects of APA could be reversed by aspartic acid or asparagine, among the amino acids, and by intermediates of the tricarboxylic acid cycle, with the exception of alpha-ketoglutarate and fumarate. Formate, malonate, and certain other organic acids also possessed this ability. Succinate was the best reversing agent. Fluoroacetic acid (FAA) also inhibited sporulation, but had no effect on vegetative growth or germination of spores of B. cereus T. Unlike APA, FAA inhibited sporulation even when added after the pH of the culture had started to rise. Bisulfite was similar to FAA in its effects on sporulation. With the exception of pyruvate, acetate, aspartate, and malate, most of the compounds reversing the effects of APA also overcame the effects of FAA or bisulfite on sporulation. Esters of some of the acids reversing the effects of the above inhibitors were studied for their action on germination, growth, and sporulation. Ethyl pyruvate prevented germination of the spores, slowed down growth, and inhibited sporulation. Ethyl malonate and ethyl succinate inhibited only sporulation. All the above inhibitors prevented the synthesis of dipicolinic acid (DPA) also. When B. cereus T was grown in the absence of glucose (in extracted yeast extract-minerals medium), the above inhibitors had no effect on sporulation. Ethyl oxamate permitted sporulation, but the spores produced were heat-sensitive. Ethyl pimelate caused lysis when added before the pH of the culture began to rise. When added after the pH of the culture began to rise, it also permitted sporulation, and the spores were sensitive to heat. (These heat-sensitive spores were refractile and dormant, and did not stain with crystal violet. However, they germinated normally, losing refractibility and became stainable.) The effect of ethyl oxamate and ethyl pimelate could be overcome by DPA. APA, FAA, ethyl malonate, and ethyl succinate also inhibit the sporulation of a number of other bacilli.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM FOOD PROCESSING COLOR FLAVOR CHEMISTRY TOXINS

Abstract  BIOSIS COPYRIGHT: BIOL ABS. A method of gas chromatographic determination of malonic ester in the air has been developed, and conditions for selecting and analyzing samples have been chosen. The proposed method is selective and allows the air concentrations of malonic ester to be estimated and may be recommended for sanitary studies.

Abstract  IPA COPYRIGHT: ASHP Diethyl phenylmalonate and methyl malonate were amidoethylated with the N-acyl aziridines under various conditions.