Search

We report a short synthetic strategy for direct preparation of (2-ketulosonyl)onate donors. These donors feature a cyclic thionocarbonate group at the C2 and C3 positions, which plays a multitude of chemical roles. It protects the C2 and C3 hydroxyls during building block preparation. In glycosylation, the thionocarbonate can be activated by a sulfenylating promoter and serves as a leaving group. Because of its β-configuration, it also plays the role of a stereo-directing group during the formation of the α-glycosidic bond. In addition, the thionocarbonate donors can couple with thioglycoside acceptors. This orthogonal property was used for the development of the first one-pot glycosylation method for 2-keto acid sugars.

Background: The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition. Methods: This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients’ nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test. Results: The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study. Conclusions: In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement(0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients’ mineral metabolism, inflammatory parameters, or body compositions. Key words: Chinese; Hemodialysis; Keto acid; Nutrition

Six optically active macroheterocycles bearing ester and dihydrazide moieties were synthesized from available natural (-)-α-pinene through the intermediate keto acid, (31R,33R)- 1-hydroxy-32,32-dimethyl-1,4-dioxopentaphane, using the [2+1] reaction of this keto acid with di- or triethylene glycols and the [1+1] condensation of the resulting α,ω-diketo diesters with dicarboxylic acid dihydrazides in the key steps.

A regioselective Rh-catalyzed decarboxylative cross-coupling of β-keto acids and alkynes to access branched γ,δ-unsaturated ketones is presented.

Maple syrup urine disease (MSUD) was first recognized as an inherited lethal encephalopathy beginning in the first week of life and associated with an unusual odor in the urine of affected children. It was later confirmed as a deficiency of branched-chain keto acid dehydrogenase (BCKDH), which is the second step in branched-chain amino acid (BCAA) breakdown. MSUD is characterized by BCAA and branched-chain keto acid (BCKA) accumulation. BCAAs are essential amino acids and powerful metabolic signals with severe consequences of both deprivation and accumulation. Treatment requires life-long dietary restriction and monitoring of BCAAs. However, despite excellent compliance, children commonly suffer metabolic decompensation during intercurrent illness resulting in life-threatening cerebral edema and dysmyelination. The mechanisms underlying brain injury have been poorly understood. Recent studies using newly developed mouse models of both classic and intermediate MSUD have yielded insight into the consequences of rapid BCAA accumulation. Additionally, these models have been used to test preliminary treatments aimed at competing with blood-brain barrier transport of BCAA using norleucine. Assessment of biochemical changes with and without treatment suggests different roles for BCAA and BCKA in the mechanism of brain injury.

Branched chain amino acids (BCAA) and keto acids (BCKA) have been used together with other essential amino acids (EAA) and keto analogues for nutritional therapy in chronic uremia, generally combined with low protein diets. With most EAA or keto acid — amino acid (KAA/EAA) preparations available nitrogen balance during long-term treatment is slightly negative, and plasma and muscle amino acid concentrations fail to normalize. However, life is prolonged, uremic symptoms are reduced and several nutritional parameters may improve as a results of such treatment. KEA/EEA preparations which contain BCKA as their calcium salts may decrease serum phosphate along with an increase in serum calcium and a fall in serum parathyroid hormone but may cause symptomatic hypercalcemia. Theoretically, supplementation with KAA/EAA may have the advantage over EAA that essential building blocks for protein may be supplied with lower total intake of nitrogen, but it is still doubtful whether there is any difference in therapeutic effects between KAA/EAA and EAA in conventional proportions. A new EAA preparation with modified proportions of BCAA (VAL > LEU > ILE) seems to be superior since it normalizes intracellular BCAA concentrations and results in positive nitrogen balance during long-term therapy.

A highly diastereoselective, nucleophile-promoted bis-cyclization process, employing readily available and tractable keto acid substrates, is described. This methodology provides concise access to bicyclic- and tricyclic-beta-lactones bearing tertiary carbinol centers and quaternary carbons, greatly extending the scope of previous routes to bicyclic-beta-lactones from aldehyde acid substrates. The utility of the method was demonstrated by application to an enantioselective synthesis of (+)-dihydroplakevulin A. This and related processes may be revealing a subtle interplay between [2+2] cycloaddition and nucleophile-catalyzed aldol lactonization (NCAL) reaction manifolds.

Kynurenine aminotransferase (KAT) catalyzes the formation of kynurenic acid (KYNA), the natural antagonist of ionotropic glutamate receptors. This study tests potential substrates and assesses the effects of amino acids and keto acids on the activity of mosquito KAT. Various keto acids, when simultaneously present in the same reaction mixture, display a combined effect on KAT catalyzed KYNA production. Moreover, methionine and glutamine show inhibitory effects on KAT activity, while cysteine functions as either an antagonist or an inhibitor depending on the concentration. Therefore, the overall level of keto acids and cysteine might modulate the KYNA synthesis. Results from this study will be useful in the study of KAT regulation in other animals.

The stereochemical outcome of cyclocondensation reactions of racemic and prochiral aldehyde and keto acid derivatives with (R)-phenylglycinol, leading to 7-substituted pyrrolidine-derived bicyclic lactams, is described.

Recent advances in computational approaches for creating pathways for novel biochemical reactions has motivated the development of approaches for identifying enzyme-substrate pairs that are attractive candidates for effecting catalysis. We present an improved structural-based strategy to probe and study enzyme-substrate binding based on binding geometry, energy, and molecule characteristics, which allows for in silico screening of structural features that imbue higher catalytic potential with specific substrates. The strategy is demonstrated using 2-keto acid decarboxylation with various pairs of 2-keto acids and enzymes. We show that this approach fitted experimental values for a wide range of 2-keto acid decarboxylases for different 2-keto acid substrates. In addition, we show that the structure-based methods can be used to select specific enzymes that may be promising candidates to catalyze decarboxylation of certain 2-keto acids. The key features and principles of the candidate enzymes evaluated by the strategy can be used to design novel biosynthesis pathways, to guide enzymatic mutation or to guide biomimetic catalyst design.

2-Cetyl-3-20 keto acid(N-ethyl perfluorinated octyl sulfonamide) N- ethyl ester was synthesized by the reaction of N-ethyl-N-hydroxyethyl perfluorinated octyl sulfonamide and alky ketene dimer. The experimental results show that the yield of products can be 89% when the molar ratio of perfluorinated octyl sulfonamide to ketene dimer is 1:1.1 and the reaction lasts about four hours at 80 °C. The structure of the product was characterized by FTIR and 1HNMR. The product can dissolve in polar solvents such as NMP, DMAC, THF, DMSO, CHCl3, and 10% weight-loss temperature measured by TGA is 202 °C.

We have induced high levels of resistance to metronidazole (1 mM or 170 microg ml(-1)) in two different strains of Trichomonas vaginalis (BRIS/92/STDL/F1623 and BRIS/92/STDL/B7708) and have used one strain to identify two alternative T. vaginalis 2-keto acid oxidoreductases (KOR) both of which are distinct from the already characterised pyruvate:ferredoxin oxidoreductase (PFOR). Unlike the characterised PFOR which is severely down-regulated in metronidazole-resistant parasites, both of the alternative KORs are fully active in metronidazole-resistant T. vaginalis. The first, KORI, localized in all membrane fractions but predominantly in the hydrogenosome fraction, is soluble in Triton X-100 and the second, KOR2, is extractable in 1 M acetate from membrane fractions of metronidazole-resistant parasites. PFOR and both KORI and KOR2 use a broad range of 2-keto acids as substrates (pyruvate, alpha-ketobutyrate, alpha-ketomalonate), including the deaminated forms of aromatic amino acids (indolepyruvate and phenylpyruvate). However, unlike PFOR neither KORI or KOR2 was able to use oz-ketoglutarate. Deaminated forms of branched chain amino acids (alpha-ketoisovalerate) were not substrates for T. vaginalis KORs. Since KOR I and KOR2 do not apparently donate electrons to ferredoxin, and are not down-regulated in metronidazole-resistant parasites, we propose that KORI and KOR2 provide metronidazole-resistant parasites with an alternative energy production pathway(s) which circumvents metronidazole activation.

The title compound, C11H8O3, displays catemeric aggregation, involving hydrogen bonds progressing from the carboxyl of one mol­ecule to the ketone of a glide-related neighbor [O⋯O = 2.6952 (12) A and O—H⋯O = 177.7 (16)°]. The mol­ecule is highly planar and inherently achiral, but a slight conformational enanti­omerism generated by the packing creates alternating conformational chirality in the chain units. Hydrogen-bonding chains, all aligned in the a-axis direction, occur in parallel counter-directional pairs related by centrosymmetry. Significant overlap of the aromatic rings occurs in the mol­ecular stacking, at an average distance of 3.354 A. Two C—H⋯O=C close contacts exist.

The title racemate, C11H16O3, displays two different hydrogen-bonding modes in the crystal structure. The chosen asymmetric unit consists of two mol­ecules of identical handedness that differ in the rotation of their carboxyl groups and are linked by an acid-to-ketone hydrogen bond [O⋯O = 2.7219 (17) A and O—H⋯O = 174°]. The remaining carboxyl forms a centrosymmetric dimer with a second such unit [O⋯O = 2.6368 (15) A and O—H⋯O = 174°], while the ketones at the extremities of this four-mol­ecule aggregate remain unengaged. Five inter­molecular C—H⋯O close contacts were found.

In the title crystal structure, C9H14O3·H2O, the water molecule accepts a hydrogen bond from the carboxyl group [O...O = 2.6004 (13) Å and O—H...O = 163°], while donating hydrogen bonds to the ketone [O...O = 2.8193 (14) Å and O—H...O = 178 (2)°] and the acid carbonyl groups [O...O = 2.8010 (14) Å and O—H...O = 174 (2)°]. This creates a network of hydrogen bonds confined within a continuous flat ribbon two molecules in width and extending in the [101] direction.

Seven novel cadinane sesquiterpenes, including the seven-membered endoperoxide lactone arteannuin H (1), two six-membered lactones arteannuins I (4) and J (5), three five-membered lactones arteannuins K-M (6–8) and a keto acid arteannuin N (9) have been isolated from the dried leaves of Artemisia annua in addition to the known compounds dihydroartemisinic acid (27), dihydroarteannuin B (24) and dihydro-epi-deoxyarteannuin B (22). It is proposed that these novel sesquiterpenes are biogenetically related to dihydroartemisinic acid via intermediate secondary and tertiary allylic hydroperoxides.

The title compound, C10H8O3, aggregates in the crystal structure as catemers, whose hydrogen bonding progresses from the carboxyl to the ketone of a neighboring screw-related mol­ecule along the b axis [O⋯O = 2.6481 (12) A and O—H⋯O = 169°]. Four hydrogen-bonding chains in centrosymmetric pairs pass through the cell in the b-axis direction. Two inter­molecular C—H⋯O=C close contacts are found, involving both the ketone and acid functions.

D-amino acid oxidase (DAAO, EC 1. 4. 3. 3) converts D-amino acid to a corresponding α-keto acid via deamination. D-amino acid oxidase is one of the most important enzymes responsible for maintenance proper level of D-amino acids, which play a key role in regulation of many processes in living cells. This paper summary the applications of D-amino acid oxidase in agricultural and industry practices, as the target in human disease treatments, etc. Most important of all, we demonstrate the importance of metagenomic library in exploring the novel D-amino acid oxidase from the environmental microbiology to optimize their applications.

The two title compounds exhibit strikingly different hydrogen-bonding modes. The monoacid C 12 H 8 O 3 , (I) (alternative systematic name: 7-oxo-7H-benzocycloheptene-6-carboxylic acid), adopts a nearly planar conformation with the carboxyl internally hydrogen-bonded to the ketone; the molecules pack in stacks at an interplanar distance of 3.397 (4) A with six lateral C=O...H-C close contacts. In the diacid C 13 H 8 O 5 , (II) (alternative systematic name: 7-oxo-7H-benzocycloheptene-6,8- dicarboxylic acid), the ketone carbonyl, which is not involved in hydrogen bonding, lies out of the general molecular plane, while the carboxylic acids are paired by hydrogen bonding with those of neighboring molecules, forming flat zigzag chains. Both (I) and (II) adopt slightly asymmetric conformations.

An advance in the asymmetric, nucleophile-catalyzed aldol lactonization process with keto acid substrates is described.

The an­hydrous form, (I), of the title compound, (−)-2-(1,2,3,4,4a,7-hexa­hydro-4a,8-di­methyl-1,7-dioxo-2-naphthyl)­propionic acid, C15H18O4, derived from a naturally occurring sesquiterpenoid, has two mol­ecules in the asymmetric unit, (I) and (I′), differing in the conformations of the saturated ring and the carboxyl group. The compound aggregates as carboxyl-to-ketone hydrogen-bonding catemers [O⋯O = 2.776 (3) and 2.775 (3) A]. Two crystallographically independent sets of single-strand hydrogen-bonding helices with opposite end-to-end orientation pass through the cell in the b direction, one consisting exclusively of mol­ecules of (I) and the other entirely of (I′). Three C—H⋯O=C close contacts are found in (I). The monohydrate, C15H18O4·H2O, (II), with two mol­ecules of (I) plus two water mol­ecules in its asymmetric unit, forms a complex three-dimensional hydrogen-bonding network including acid-to-water, water-to-acid, water-to-ketone, water-to-water and acid-to-acid hydrogen bonds, plus three C—H⋯O=C close contacts. In both (I) and (II), only the ketone remote from the acid is involved in hydrogen bonding.

The formation of an inclusion compound and the interaction of both ionic and hydrogen bonding were shown to be indispensable in the asymmetric reduction of keto acid in the presence of 6-deoxy-6-amino-β-cyclodextrin with NaBH4 in an aqueous buffer solution. Furthermore, multiple interactions were elucidated and the enantioface differentiating reduction was induced in the concerted interactions. A mechanistic scheme for the enantioface differentiating attack of a reducing-reagent on the included substrate was suggested.

COMPREHENSIVETREATMENTstrategy for chronic kidney disease (CKD) patients, including dietary protein restriction supplemented with keto acids/amino acids, can yield benefits in terms of nitrogen-compound retention, metabolic acidosis, calcium-phosphorus metabolism abnormalities, peripheral insulin resistance,andevenpostponementofrenalreplacement therapy. These benefits will be realized if enough essentialaminoacidsareprovided,whileavoidinganaccumulation of unexcreted, potentially toxic ions and metabolic products arising from the breakdown of foods rich in protein. Furthermore, keto acids capture excessive nitrogen residues and use themforessentialaminoacidproduction.Thus,nitrogen intake can be restricted, and endogenous ureaformationisreduced.Ketoacidscanfullysubstitute for their respective essential amino acids in terms of maintaining nutritional status, because these compounds maintain a neutral nitrogen balance, even when they are given to CKD patients who have no other source of essential amino acids. Several studies showed that in experimental models of CKD, a high-protein diet worsens renal damage and increases proteinuria, hypertension, and mortality. In contrast, a long-term, proteinrestricted diet can slow the rate of renal failure, and attenuate the impact of hemodynamic and

γ- and δ-Lactones 5, 6, 13, 14, 15 and 16 were synthesized via baker's yeast reduction of the corresponding keto acids 3, 4 and 9–12. The enantioselectivity of the reduction is strongly dependent on the nature of the keto acid; the δ-lactones ware always obtained in an ee% higher than the γ-lactones and ranging from 70% to 100%.

The title ketocarboxylic acid [systematic name: (5R,8R,9S,10S,13R,14S,17R,20R)-3-oxo-24-norcholanic acid], C(23)H(36)O(3), forms acid-to-acid hydrogen-bonding chains [O...O = 2.620 (2) A and O-H...O = 163 (3) degrees ] in which all carboxyl groups adopt the rare anti conformation, while the ketone group does not participate in the hydrogen bonding. The occurrence and energetics of this conformation are discussed. One intermolecular C-H...O close contact exists, which plays a role in stabilizing the hydrogen-bonding arrangement.

The crystal structure of the title compound, (±)-cis-2-oxoperhydronaphthalene-4a-acetic acid, C12H18O3, involves hydrogen-bonding catemers. Hydrogen bonds progress from the carboxyl group of one molecule to the ketone group of a translationally related neighbor [O⋯O 2.715 (3) A]. Eight parallel hydrogen-bonding chains proceed in the a direction through the chosen cell. Two C=O⋯H—C close contacts were found, involving the acid carbonyl group.

The crystal structure of the title compound (C11H10O3) contains hydrogen-bonded centrosymmetric carboxyl dimers. Significant carboxyl disorder was found, and was modeled by two rotational conformers, yielding two O⋯O distances of 2.649 (14) and 2.666 (17) A.

The title keto-carboxylic acid, C 13 H 12 O 3 , forms spiral carboxyl-to-ketone hydrogen-bonding catemers, whose helical axes are parallel to the b cell axis. Two single-strand hydrogen-bonding chains pass through the cell, each composed of molecules of a single chirality.

9-Oxo-9H-fluorene-1-carboxylic acid, C 14 H 8 O 3 , adopts a planar conformation with the carboxyl group internally hydrogen bonded to the ketone O atom. The molecules stack in the a direction [a = 3.809 (1)A], with an interplanar separation of 3.496 (4) A.

In the title compound, C 14 H 16 O 3 , enantiomeric pairs of molecules form dimers by mutual hydrogen bonding of carboxyl groups, with the ketone group not involved in the hydrogen bonding. The components of the dimer differ in conformation, so that the dimer is the asymmetric unit.

In the title compound, C 14 H 16 O 3 .0.25H 2 O, enantiomeric pairs of molecules form centrosymmetric dimers by mutual hydrogen bonding of carboxyl groups ; the dimers are centered on the b and c edges of the chosen unit cell. The ketone has a close contact of 2.738 (7)A to the O atom of a water molecule (which has an occupancy of approximately 25%).

In the title compound, C 8 H 12 O 3 , enantiomeric pairs of molecules form centrosymmetric dimers by mutual hydrogen bonding of carboxyl groups, with the ketone not involved in the hydrogen bonding. The dimers are of four types, centered on the three edges and the center of the cell. The carboxyl C-O bond lengths and angles are substantially disordered. There is a 2.551(3) A intermolecular contact between methine H and ketone O atoms.

The title monohydrate, C(7)H(10)O(3).H(2)O, aggregates as a complex hydrogen-bonding network, in which the water molecule accepts a hydrogen bond from the carboxyl group of one molecule and donates hydrogen bonds to ketone and carboxyl C=O functions in two additional molecules, yielding a sheet-like structure of parallel ribbons. The keto acid adopts a chiral conformation through rotation of the carboxyl group by 62.50 (15) degrees relative to the plane defined by its point of attachment and the ketone C and O atoms. Two C-H.O close contacts exist in the structure.

The gene coding for the transacylase subunit (DBT) of the human branched-chain keto acid dehydrogenase complex was localized to chromosome 1 by probing panels of human × mouse chromosome hybrids with an E2 cDNA amplified by the polymerase chain reaction. Additional data with two hybrids containing chromosome 1 fragments suggest that the DBT gene is located on the short arm (1pter→p21) of the chromosome.

In living cells, proteins are generally unstable compounds, and are continually broken down and resynthesized. Proteins are easily denatured and even the most robust of them lose their activity over time. The needs of many cells vary from minute to minute and cells of all organisms adapt to this by changing, to varying extents, the proteins which they make and hence the functions which they are able to perform.

In the last few years we developed in our laboratory chromatographic methods for the chiral discrimination of amino acids, which allow to study the occurrence and the role of D-amino acids in nature. In the present paper we show that a methionine-auxotroph the eukaryotic yeast Kluyveromices lactis CBS 2359/152 is able to utilize D-methionine. Feeding yeast cells with either L-or D-methionine, we determined either enantiomer in the medium and inside the cells. We were able to demonstrate that D-methionine is uptaken and converted to the L-enantiomer.

The title compound, C15H16O3, aggregates as hydrogen-bonded catemers progressing from each carboxyl to the ketone of a screw-related neighbor [O...O = 2.6675 (14) Å and O—H...O = 170°]. Two parallel centrosymmetrically related single-strand hydrogen-bonding helices proceed through the cell in the b-axis direction. The packing includes three intermolecular C—H...O=C close contacts, involving both the ketone and the carboxyl group. The structure is isomorphous with that of the previously described Δ4 α,β-unsaturated ketone.

The title keto acid, C16H18O3, displays significant twisting of all three ethylene bridges in its bicyclo[2.2.2]octane structure owing to steric interactions; the bridgehead-to-bridgehead torsion angles are 13.14 (12), 13.14 (13) and 9.37 (13)°. The compound crystallizes as centrosymmetric carboxyl dimers [O...O = 2.6513 (12) Å and O—H...O = 178°], which have two orientations within the cell and contain no significant carboxyl disorder.

Renal hemodynamics (Cinutest, CPAH) were measured in 5 volunteers (23–28 years of age), before and after each of the following 1-week regimen: a) low protein diet as 50% of usual intake (LPD); b) LPD + 0.6 g/kg of a mixture of essential and non essential amino acids (AAmix); c) LPD + 0.6 g/kg of branched chain amino acids (BCAA); d) LPD + 0.15 g/kg of essential amino and Keto acid supplement (EAKA). LPD induced a decrease in renal plasma flow (RPF) without GFR variation; this finding was annulled when LPD was supplemented either with AAmix or EAKA, suggesting that EAKA used as supplement of LPD in chronic renal disease could counterbalance the low-protein induced reduced glomerular hemodynamic load. BCAA tended to antagonize the LPD renal effects: these data were partially inconsistent with the renal vasoconstriction we previously observed during BCAA infusion in normal man.

The title racemate (C11H14O3) aggregates in the solid as acid-to-ketone hydrogen-bonding catemers [O⋯O = 2.6557 (13) A and O—H⋯O = 170°], whose components are glide-related. The stereochemistry of the carboxyl group arises spontaneously during the synthesis. One inter­molecular C—H⋯O=C close contact was found.

The acylated cyclic enamino ester dipeptide analogues 12, 13, and 17-10 have been prepared via lactonization of the keto acid phosphorane 8 followed by incorporation of an amino acid into the product enol lactones