Chiral discrimination of secondary alcohols and carboxylic acids by NMR spectroscopy

The manuscript reports two novel ternary ion-pair complexes, which serve as chiral solvating agents, for enantiodiscrimination of secondary alcohols and carboxylic acids. The protocol for discrimination of secondary alcohols is designed by using one equivalent mixture each of enantiopure mandelic acid, 4-dimethylaminopyridine (DMAP) and a chiral alcohol. For discrimination of carboxylic acids, the ternary complex is obtained by one equivalent mixture each of enantiopure chiral alcohol, DMAP and a carboxylic acid. The designed protocols also permit accurate measurement of enantiomeric composition. Copyright (C) 2014 John Wiley & Sons, Ltd.

Hydrogen energy future with formic acid: a renewable chemical hydrogen storage system

Formic acid, the simplest carboxylic acid, is found in nature or can be easily synthesized in the laboratory (major by-product of some second generation biorefinery processes); it is also an important chemical due to its myriad applications in pharmaceuticals and industry. In recent years, formic acid has been used as an important fuel either without reformation (in direct formic acid fuel cells, DFAFCs) or with reformation (as a potential chemical hydrogen storage material). Owing to the better efficiency of DFAFCs compared to several other PEMFCs and reversible hydrogen storage systems, formic acid could serve as one of the better fuels for portable devices, vehicles and other energy-related applications in the future. This perspective is focused on recent developments in the use of formic acid as a reversible source for hydrogen storage. Recent developments in this direction will likely give access to a variety of low-cost and highly efficient rechargeable hydrogen fuel cells within the next few years by the use of suitable homogeneous metal complex/heterogeneous metal nanoparticle-based catalysts under ambient reaction conditions. The production of formic acid from atmospheric CO2 (a greenhouse gas) will decrease the CO2 content and may be helpful in reducing global warming.

Conformation-activity correlations for chemotactic tripeptide analogs incorporating dialkyl residues with linear and cyclic alkyl sidechains at position 2

Five stereochemically constrained analogs of the chemotactic tripeptide incorporating 1-aminocycloalkane-1-carboxylic acid (Ac(n)c) and alpha,alpha-dialkylglycines (Deg, diethylglycine; Dpg, n,n-dipropylglycine and Dbg, n,n-dibutylglycine) at position 2 have been synthesized. NMR studies of peptides For-Met-Xxx-Phe-OMe (Xxx = Ac(7)c, I; Ac(8)c, II; Deg, III; Dpg, IV and Dbg, V; For, formyl) establish that peptides with cycloalkyl residues, I and II, adopt folded beta-turn conformations in CDCl3 and (CD3)(2)SO. In contrast, analogs with linear alkyl sidechains, III-V, favour fully extended (C-5) conformations in solution. Peptides I-V exhibit high activity in inducing beta-glucosaminidase release from rabbit neutrophils, with ED(50) values ranging from 1.4-8.0 x 10(-11)M. In human neutrophils the Dxg peptides III-V have ED(50) values ranging from 2.3 x 10(-8) to 5.9 x 10(-10) M, with the activity order being V > IV > III. While peptides I-IV are less active than the parent. For-Met-Leu-Phe-OH, in stimulating histamine release from human basophils, the Dbg peptide V is appreciably more potent, suggesting its potential utility as a probe for formyl peptide receptors.

First donor-acceptor interaction promoted gelation of organic fluids

In recent years there has been considerable interest in developing new types of gelators of organic solvents.1 Despite the recent advances, a priori design of a gelator for gelling a given solvent has remained a challenging task. Various noncovalent interactions like hydrogen-bonding,2 metal coordination3 etc. have been used as the driving force for the gelation process. A special class of cholesterol-based gelators were reported by Weiss,4 and by Shinkai.5 Gels derived from these molecules have been used for chiral recognition/sensing,6 for studying photo- and metal-responsive functions,7 and as templates to make hollow fiber silica.8 Other types of organogels have been used for designing polymerized 9 and reverse aerogels,10 and in molecular imprinting.11 Hanabusa’s group has recently reported organogels with a bile acid derivative.12 This has prompted us to disclose our results on a novel electron donor–acceptor (EDA) interaction mediated two-component13 gelator system based on the bile acid14 backbone.

Antimycobacterial activities of novel fluoroquinolones

Fifty-one novel 1-(cyclopropyl/2,4-difluorophenyl/t-butyl)-1,4-dihydro-6-fluoro-7-(sub secondary amino)-4-oxoquinoline-3-carboxylic acids were synthesized and evaluated for their antimycobacterial in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC 2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 7-(3-(diethylcarbamoyl)piperidin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (7I) was found to be the most active compound in vitro with MIC of 0.09 mu M against MTB and MDR-TB respectively. In the in vivo animal model 7I decreased the mycobacterial load in lung and spleen tissues with 2.53- and 4.88-log10 protections respectively at a dose of 50 mg/kg body weight. (C) 2007 Elsevier Masson SAS. All rights reserved.

Studies in terpenoids. Part 42. Synthesis of 3-(2-hydroxyisopropyl)5,8-dimethyl-1,2-naphthoquinone (emmotin-H)

Emmotin-H, a naturally occurring sesquiterpenoid 1,2-naphthoquinone pigment (1) has been synthesised in a four step sequence starting from the known 5,8-dimethyl-4-oxotetralin-2-carboxylic acid (3a). Selenium dioxide oxidation of its methyl ester (3b) gives 3-methoxycarbonyl-5,8-dimethyl-1,2-naphthoquinone (4) which on reductive acetylation affords the corresponding diacetoxynaphthalene ester (5). Its reaction with excess of methylmagnesium iodide is accompanied by aerial oxidation during work-up and furnishes emmotin-H (1).

Linalyl Acetate Is Metabolized by Pseudomonas incognita with the Acetoxy Group Intact

Metabolism of linalyl acetate by Pseudomonas incognita isolated by enrichment culture on the acyclic monoterpene alcohol linalool was studied. Biodegradation of linalyl acetate by this strain resulted in the formation of linalool, linalool- 8-carboxylic acid, oleuropeic acid, and A5-4-acetoxy-4-methyl hexenoic acid. Cells adapted to linalyl acetate metabolized linalyl acetate-8-aldehyde to linalool- 8-carboxylic acid, linalyl acetate-8-carboxylic acid, A5-4-acetoxy-4-methyl hexenoic acid, and geraniol-8-carboxylic acid. Resting cell suspensions previously grown with linalyl acetate oxidized linalyl acetate-8-aldehyde to linalyl acetate-8- carboxylic acid, A5-4-acetoxy-4-methyl hexenoic acid, and pyruvic acid. The crude cell-free extract (10,000 g of supernatant), obtained from the sonicate of linalyl acetate-grown cells, was shown to contain enzyme systems responsible for the formation of linalyl acetate-8-carboxylic acid and linalool-8-carboxylic acid from linalyl acetate. The same supernatant contained NAD-linked alcohol and aldehyde dehydrogenases involved in the formation of linalyl acetate-8-aldehyde and linalyl acetate-8-carboxylic acid, respectively. On the basis of various metabolites isolated from the culture medium, resting cell experiments, growth and manometric studies carried out with the isolated metabolites as well as related synthetic analogs, and the preliminary enzymatic studies performed with the cellfree extract, a probable pathway for the microbial degradation of linalyl acetate with the acetoxy group intact is suggested.

The structure of monopotassium phosphoenolpyruvate

CaH406P-.K +, M r = 206.10, is orthorhombic, space group Pbca (from systematic absences), a = 14.538(4), b = 13.364(5), c = 6.880 (6)A, U = 1383.9 A 3, D x = 2.07 Mg m -a, Z = 8, ~.(Mo Ka) = 0.7107/~, p(MO Ka) = 1.015 mm -1. The final R value is 0.042 for a total of 1397 reflections. The high energy P-O(13) and the enolic C(1)-O(13) bonds are 1.612 and 1.374 A respectively. The enolpyruvate moiety is essentially planar. The orientation of the phosphate with respect to the pyruvate group in PEP.K is distinctly different from that in the PEP-cyclohexylammonium salt, the torsion angle C (2)-C (1)-O(13)- P being -209.1 in the former and -90 ° in the latter. The K + ion binds simultaneously to both the phosphate and carboxyl ends of the same PEP molecule. The ester O(13) is also a binding site for the cation. The K + ion is coplanar with the pyruvate moiety and binds to 0(22) and O(13) almost along their lone-pair directions. The carbonyl 0(22) prefers to bind to the K + ion rather than take part in the formation of hydrogen bonds usually observed in carboxylic acid structures.

Metabolism of alpha-terpineol by Pseudomonas incognita

Details of the metabolism of alpha-terpineol by Pseudomonas incognita are presented. Degradation of alpha-terpineol by this organism resulted in the formation of a number of acidic and neutral metabolites. Among the acidic metabolites, beta-isopropyl pimelic acid, 1-hydroxy-4-isopropenyl-cyclohexane-1-carboxylic acid, 8-hydroxycumic acid, oleuropeic acid, cumic acid, and p-isopropenyl benzoic acid have been identified. Neutral metabolites identified were limonene, p-cymene-8-ol, 2-hydroxycineole, and uroterpenol. Cell-free extracts prepared from alpha-terpineol adapted cells were shown to convert alpha-terpineol, p-cymene-8-ol, and limonene to oleuropeic acid, 8-hydroxycumic acid, and perillic acid, respectively, in the presence of NADH. The same cell-free extract contained NAD+ -specific dehydrogenase(s) which converted oleuropyl alcohol, p-cymene-7,8-diol, and perillyl alcohol to their corresponding 7-carboxy acids. On the basis of various metabolites isolated from the culture medium, together with the supporting evidence obtained from enzymatic and growth studies, it appears that P. incognita degrades alpha-terpineol by at least three different routes. While one of the pathways seems to operate via oleuropeic acid, a second may be initiated through the aromatization of alpha-terpineol. The third pathway may involve the formation of limonene from alpha-terpineol and its further metabolism.

Metabolism of structurally modified acyclic monoterpenes by Pseudomonas incognita

The ability of Pseudomonas incognita to metabolize some structurally modified acyclic monoterpenes was tested. The 6,7 double bond was found essential for these compounds to serve as a substrate for this organism, whereas the same was not true with the 1,2 double bond. Metabolism of dihydrolinalyl acetate by this strain yielded dihydrolinalool, dihydrolinalool-8-carboxylic acid, dihydrolinalyl acetate-8-carboxylic acid, and 4-acetoxy-4-methyl hexanoic acid. A cell-free extract prepared from dihydrolinalyl acetate grown cells transformed dihydrolinalyl acetate into dihydrolinalool and dihydrolinalool-8-carboxylic acid. Based on the identification of various metabolites isolated from the culture medium, and on growth and manometric studies carried out with the isolated metabolites as well as with related synthetic analogs, probable pathways for the biodegradation of dihydrolinalyl acetate are presented.

Structural Crystallography and Crystal Chemistry

CaH406P-.K +, M r = 206.10, is orthorhombic, space group Pbca (from systematic absences), a = 14.538(4), b = 13.364(5), c = 6.880 (6)A, U = 1383.9 A 3, D x = 2.07 Mg m -a, Z = 8, ~.(Mo Ka) = 0.7107/~, p(MO Ka) = 1.015 mm -1. The final R value is 0.042 for a total of 1397 reflections. The high energy P-O(13) and the enolic C(1)-O(13) bonds are 1.612 and 1.374 A respectively. The enolpyruvate moiety is essentially planar. The orientation of the phosphate with respect to the pyruvate group in PEP.K is distinctly different from that in the PEP-cyclohexylammonium salt, the torsion angle C (2)-C (1)-O(13)- P being -209.1 in the former and -90 ° in the latter. The K + ion binds simultaneously to both the phosphate and carboxyl ends of the same PEP molecule. The ester O(13) is also a binding site for the cation. The K + ion is coplanar with the pyruvate moiety and binds to 0(22) and O(13) almost along their lone-pair directions. The carbonyl 0(22) prefers to bind to the K + ion rather than take part in the formation of hydrogen bonds usually observed in carboxylic acid structures.

Conformations of Heterochiral and Homochiral Proline-Pseudoproline Segments in Peptides: Context Dependent Cis-Trans Peptide Bond Isomerization

The pseudoproline residue (Psi Pro, L-2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid) has been introduced into heterochiral diproline segments that have been previously shown to facilitate the formation of beta-hairpins, containing central two and three residue turns. NMR studies of the octapeptide Boc-Leu-Phe-Val-(D)Pro-Psi Pro-Leu-Phe-Val-OMe (1), Boc-Leu-Val-Val-(D)Pro-Psi Pro-Leu-Val-Val-OMe (2), and the nonapeptide sequence Boc-Leu-Phe-Val-(D)Pro-Psi Pro-(D)Ala-Leu-Phe-Val-OMe (3) established well-registered beta-hairpin structures in chloroform solution, with the almost exclusive population of the trans conformation for the peptide bond preceding the Psi Pro residue. The beta-hairpin conformation of 1 is confirmed by single crystal X-ray diffraction. Truncation of the strand length in Boc-Val-(D)Pro-Psi Pro-Leu-OMe (4) results in air increase in the population of the cis conformer, with a cis/trans ratio of 3.65. Replacement of Psi Pro in 4 by (L)Pro in 5, results in almost exclusive population of the trans form, resulting in an incipient beta-hairpin conformation, stabilized by two intramolecular hydrogen bonds. Further truncation of the sequence gives an appreciable rise in the population of cis conformers in the tripeptide piv-(D)Pro-Psi Pro-Leu-OMe (6). In the homochiral segment Piv-Pro Psi Pro-Leu-OMe (7) only the cis form is observed with the NMR evidence strongly supporting a type VIa beta-turn conformation, stabilized by a 4 -> 1 hydrogen bond between the Piv (CO) and Leu (3) NH groups. The crystal structure of the analog peptide 7a (Piv-Pro-Psi(H,CH3)Pro-Leu-NHMe) confirms the cis peptide bond geometry for the Pro-Psi(H,CH3)pro peptide bond, resulting in a type VIa beta-turn conformation.

Palladium(II) and platinum(II) complexes of beta-functionalized ethyl selenolates: Effect of substitution on synthesis, reactivity, spectroscopy, structures and thermal behavior

Sodium ethylselenolates with functional groups X (where X = -OH, -COOH, -COOMe and -COOEt) at beta-carbon were prepared in situ by reductive cleavage of corresponding diselenide with NaBH4 either in methanol or aqueous ammonia. Treatment of these selenolates with [M2Cl2(mu-Cl)(2)(PR'(3))(2)] (M = Pd or Pt; PR'(3) = PMePh2, PnPr(3)) in different stoichiometry yielded various bi- and tri-nuclear complexes. The homoleptic hexanuclear complexes [Pd(mu-SeCH2CH2X)(2)](6) (X = OH, COOH, COOEt), were obtained by reacting Na2PdCl4 with NaSeCH2CH2X. All these complexes have been fully characterized. Molecular structures of ethylselenolates containing hydroxyl and carboxylic acid groups revealed solid state associated structures through inter-molecular hydrogen bond interactions. Trinuclear complex, [Pd3Cl2(mu-SeCH2CH2COOH)(4)(PnPr(3))(2)] (3a), was disposed in a boat form unlike chair conformation observed for the corresponding methylester complex. The effect of beta-functionality in ethylselenolate ligands towards reactivity, structures and thermal properties of palladium and platinum complexes has been extensively Studied.

Asymmetric total synthesis of erythromycin. 2. Synthesis of an erythronolide A lactone system

In reporting a total synthesis of erythromycin (la) we described in the preceding paper1 the synthesis of the erythronolide A seco acid derivative 2 in optically active form. In this paper we wish to report a successful transformation of 2 to 12 (synthetically equivalent to erythronolide A) via lactonization and also demonstrate that the proper functionalization of a substrate is critical for the successful lactonization.

Functional interaction of diphenols with polyphenol oxidase - Molecular determinants of substrate/inhibitor specificity SO FEBS JOURNAL

Polyphenol oxidase (PPO) catalyzes the oxidation of o-diphenols to their respective quinones. The quinones autopolymerize to form dark pigments, an undesired effect. PPO is therefore the target for the development of antibrowning and antimelanization agents. A series of phenolic compounds experimentally evaluated for their binding affinity and inhibition constants were computationally docked to the active site of catechol oxidase. Docking studies suggested two distinct modes of binding, dividing the docked ligands into two groups. Remarkably, the first group corresponds to ligands determined to be substrates and the second group corresponds to reversible inhibitors. Analyses of the complexes provide structural explanations for correlating subtle changes in the position and nature of the substitutions on o-diphenols to their functional properties as substrates and inhibitors. Higher reaction rates and binding are reckoned by additional interactions of the substrates with key residues that line the hydrophobic cavity. The docking results suggest that inhibition of oxidation stems from an interaction between the aromatic carboxylic acid group and the apical His 109 of the four coordinates of the trigonal pyramidal coordination polyhedron of CuA. The spatial orientation of the hydroxyl in relation to the carboxylic group either allows a perfect fit in the substrate cavity, leading to inhibition, or because of a steric clash flips the molecule vertically, facilitating oxidation. This is the first study to explain, at the molecular level, the determinants Of substrate and inhibitor specificity of a catechol oxidase, thereby providing a platform for the design of selective inhibitors useful to both the food and pharmaceutical industries.