Major Isomer Research Articles

Stepwise pyrolysis of the kerogen from the Huadian oil shale, NE China: Algaenan-derived hydrocarbons and mid-chain ketones

Kerogen from the organic rich Eocene Huadian oil shale in NE China was subjected to sequential stepwise pyrolysis at 50°C intervals from 310°C to 610°C. This allowed generation of compounds according to the strength of the bonds linking them to the kerogen and thus permitted identification of compounds that were only minor constituents of one step flash pyrolysis at high temperatures such as Curie point 610°C. Pyrolysis at 310°C and 360°C yielded very small amounts of n-alkanes having a distribution similar to that of the extractable hydrocarbons, which were presumed to be occluded within the kerogen since pyrolytic products such as n-alkenes were only minor constituents. Also present was the C18 isoprenoid ketone (6,10,14-trimethylpentadecane-2-one). The pyrolyzate at 410°C showed a full suite of n-alkanes with a small amount of the corresponding n-alkenes, indicating that some cleavage of alkyl chains from the kerogen matrix had occurred. These showed a very low odd/even predominance apart from local maxima at n-C23 and n-C27. The major component was prist-1-ene, which co-occurred with a small amount of the later eluting prist-2-ene. We speculate that the pristenes were generated from tocopherols (or their oxidized products) bound to the kerogen by single, easily cleaved, CO bonds. C15–C20 isoprenoid alkanes were also observed and these might derive in part from breakdown of the isoprenoid-based algaenan produced by Botryococcus race L. The 460°C pyrolyzate contained a dominant series of n-alkene/n-alkane pairs as well as a series of novel long chain C30–C37 mid-chain ketones showing no odd/even predominance. The C35 ketone was most abundant, with only traces of higher homologues. Mass spectra showed only minor amounts of fragments due to different positions of the carbonyl group and the major isomer in all cases was assigned as the alkan-ω24-one. It seems likely that these ketones are derived from pyrolysis of algaenan that had been incorporated into the kerogen, although no previous reports have identified this chain length range or position of the carbonyl group. Some similarities with the pyrolysis products of algaenan derived from eustigmatophytes were noted. In addition, a series of n-alkan-2-ones were present, which also likely result from pyrolytic breakdown of algaenan. At pyrolysis temperatures of 510°C and 560°C, the pyrolyzates were dominated by n-alkene/n-alkane pairs with a greater proportion of alkenes and short chain hydrocarbons at the higher temperature. Only very small quantities of hydrocarbons were liberated at 610°C, indicating that lower pyrolysis temperatures can be used to study immature kerogens. Our results demonstrate that stepwise pyrolysis can be a useful means for studying components of kerogens that differ in bond strength and for elucidating specific substructures related to algaenan. The data confirm that preservation of algaenan in the Huadian oil shale is a key factor in explaining its high organic content.

The conformational structure of adenosine molecules, isolated in low-temperature Ar matrices

FTIR spectra of adenosine (Ado) molecules, isolated in low-temperature matrices, are obtained in the infrared range of 3800–400 cm−1, with a resolution of 0.3. MP2 and DT/B3LYP quantum-mechanical methods are used to calculate the population of major structural Ado isomers. It is shown that Ado can withstand prolonged evaporation at a temperature of 465 K without thermal decomposition. The structure five major conformers that are fixed in Ar matrices at 6 K, are established. Ado anti-conformers with intramolecular hydrogen bonds O2′H-N3, are found. The population of these anti-conformers is more than one and a half times less than the syn-conformer population having the intramolecular hydrogen bond O5′H-N3. In low-temperature matrices, the majority of the dominant conformers are fixed with a C2′-endo ribose ring structure. Similar to 2′-deoxyadenosine (dA), Ado conformers with intramolecular hydrogen bonds O3′H-O5 or O5′H-O3 were not found.

Understanding the Boron-Nitrogen Interaction and Its Possible Implications in Drug Design.

2-Aminoethoxydiphenylborate (2-APB) is a broad-spectrum modulator of various membrane proteins. Specifically, it exhibits concentration dependent modulation of calcium signaling through store-operated calcium (SOC) channels: low micromolar concentration of 2-APB stimulates SOC entry while a higher concentration induces complete inhibition. Ab initio quantum chemical calculations show that the relative stability of the two major isomers of 2-APB (cyclic and extended) is about 8 kcal/mol. The dual functionality of 2-APB for SOC channels is thus likely associated with its ability to switch among isomeric forms, suited to different binding sites in the SOC channels with distinct binding affinities. Importantly, the moderate relative stability of different isomers results from a delicate balance between the intramolecular boron-nitrogen coordinate bond with strength about -45 kcal/mol and ring strain engendered by cyclic oligomerization. The synergistic effect of these two factors likely makes 2-APB an ideal dual effect drug.

Cinchona Alkaloid Catalyzed Sulfa-Michael Addition Reactions Leading to Enantiopure β-Functionalized Cysteines.

Sulfa-Michael additions to α,β-unsaturated N-acylated oxazolidin-2-ones and related α,β-unsaturated α-amino acid derivatives have been enantioselectively catalyzed by Cinchona alkaloids functionalized with a hydrogen bond donating group at the C6' position. The series of Cinchona alkaloids includes known C6' (thio)urea and sulfonamide derivatives and several novel species with a benzimidazole, squaramide or a benzamide group at the C6' position. The sulfonamides were especially suited as bifunctional organocatalysts as they gave the products in very good diastereoselectivity and high enantioselectivity. In particular, the C6' sulfonamides catalyzed the reaction with the α,β-unsaturated α-amino acid derivatives to afford the products in a diastereomeric ratio as good as 93:7, with the major isomer being formed in an ee of up to 99%. The products of the organocatalytic sulfa-Michael addition to α,β-unsaturated α-amino acid derivatives were subsequently converted in high yields to enantiopure β-functionalized cysteines suitable for native chemical ligation.

Low energy CID and action IRMPD provide insights into a minor subpopulation of the gas-phase conformers of triply charged bradykinin

Unique fragmentation of the IMS-resolved conformers of triply charged bradykinin is shown to occur at very low collision energies by quadrupole CID. For the major C conformation of bradykinin, the unique fragmentation appears to result from a subpopulation that has a different average CCS than the dominant C population that has been previously identified as TTC (trans, trans, cis at the three Pro residues). The three major gas-phase isomers exhibit minimal differences in fragmentation at collision energies greater than 12eV, presumably because the amide bonds of the proline residues isomerize prior to dissociation at these higher energies. The differences in fragmentation observed in the low collision energy regime (<12eV) are attributed to the conformational differences of the fragmenting subpopulations of the mobility resolved populations associated with the cis or trans isomerization state of the three proline residues. Action IRMPD of the b2 ion supports a cis-Pro2 isomerization state for the subpopulation of conformation C fragmenting at low energies, assuming no isomerization was induced by the low energy CID. Substitution of N-methyl alanine, an acyclic proline mimic, independently, for each of the three prolines of bradykinin and low energy fragmentation of the minor subpopulation of conformation C allowed for tentative assignments of the isomerization state of two of the three proline resides of this subpopulation. Density functional theory calculations support the conclusion made from NMA-substitutions and together suggest that the subpopulation of conformation C is cis at Pro2 and trans at Pro7. It is not clear whether the minor subpopulation is a typical feature of triply charged bradykinin or whether unintended activation in the instrument used here produces this population. The results illustrate the utility of ion mobility coupled with low-energy CID for the determination of a minor subpopulation that was not visible by MS or IM alone.

Chemical characterization and antifungal activity of Poliomintha longiflora Mexican oregano

Oregano (Origanum vulgare) essential oil (EO) has been extensively examined as an antimicrobial agent; in Mexico, the study has focused on one of the Mexican oreganos, Lippia berlandieri. Thus, the aim of this research was to qualitatively and quantitatively characterize compounds present in Poliomintha longiflora EO, another of the Mexican oreganos, and to determine its antifungal activity against several phytopathogenic molds. P. longiflora EO was obtained by steam distillation; its chemical characterization was performed by GC and GC-MS, elucidating up to twenty-eight different chemical components, including thymol (37.2%), carvacrol (24.6%), isothymolmethyl ether (8.3%), and p-cymene (8.1%). Quantitative characterization of the two major isomers determined that thymol concentration (0.332 g/g) was higher than carvacrol (0.176 g/g). Minimum inhibitory concentrations (MICs) against Penicillium expansum, Aspergillus flavus, Botrytis cinerea, or Colletotrichum gloeosporioides were determined. MICs of 1.2 and 1.4 g/L of P. longiflora EO were determined for P. expansum and A. flavus, while for B. cinerea and C. gloeosporioides MICs were 0.8 and 1.0 g/L, respectively. P. longiflora EO presented three chemical components (thymol, carvacrol, and p-cymene) that provide commercial value for oreganos from this species; furthermore, the concentration of these bioactive compounds makes P. longiflora EO a good antifungal agent.

Diastereoselective Synthesis of Trisubstituted Cyclopropanes by Palladium-Catalyzed Intramolecular Allylic Alkylation of α-Aryl Esters­

We have developed a novel method for synthesizing trisubstituted cyclopropane derivatives by a palladium-catalyzed intramolecular allylic alkylation of α-aryl esters. By using α-aryl α-(methoxycarbonyl) γ-vinyl γ-lactones as substrates, decarboxylative formation of π-allylpalladium(II) intermediates followed by an intramolecular allylic alkylation of the ester enolates proceeded in the presence of 5 mol% of a palladium catalyst, producing 1-aryl-1-(methoxycarbonyl)-2-vinylcyclopropanes in good to excellent yields and high diastereoselectivities. The relative configuration of the major isomer was determined by transforming the product into a known intermediate of milnacipran synthesis. When we extended our method to asymmetric catalysis, we obtained methyl (1<i>S</i>,2<i>S</i>)-1-phenyl-2-vinylcyclopropanecarboxylate in up to 55% ee by using (<i>S</i>)-[2′-(diphenylmethoxy)-1,1′-binaphthalen-2-yl](diphenyl)phosphine as a chiral monodentate phosphorus ligand.

Kinetics and Products of the Reaction of the First-Generation Isoprene Hydroxy Hydroperoxide (ISOPOOH) with OH.

The atmospheric oxidation of isoprene by the OH radical leads to the formation of several isomers of an unsaturated hydroxy hydroperoxide, ISOPOOH. Oxidation of ISOPOOH by OH produces epoxydiols, IEPOX, which have been shown to contribute mass to secondary organic aerosol (SOA). We present kinetic rate constant measurements for OH + ISOPOOH using synthetic standards of the two major isomers: (1,2)- and (4,3)-ISOPOOH. At 297 K, the total OH rate constant is 7.5 ± 1.2 × 10(-11) cm(3) molecule(-1) s(-1) for (1,2)-ISOPOOH and 1.18 ± 0.19 × 10(-10) cm(3) molecule(-1) s(-1) for (4,3)-ISOPOOH. Abstraction of the hydroperoxy hydrogen accounts for approximately 12% and 4% of the reactivity for (1,2)-ISOPOOH and (4,3)-ISOPOOH, respectively. The sum of all H-abstractions account for approximately 15% and 7% of the reactivity for (1,2)-ISOPOOH and (4,3)-ISOPOOH, respectively. The major product observed from both ISOPOOH isomers was IEPOX (cis-β and trans-β isomers), with a ∼ 2:1 preference for trans-β IEPOX and similar total yields from each ISOPOOH isomer (∼ 70-80%). An IEPOX global production rate of more than 100 Tg C each year is estimated from this chemistry using a global 3D chemical transport model, similar to earlier estimates. Finally, following addition of OH to ISOPOOH, approximately 13% of the reactivity proceeds via addition of O2 at 297 K and 745 Torr. In the presence of NO, these peroxy radicals lead to formation of small carbonyl compounds. Under HO2 dominated chemistry, no products are observed from these channels. We suggest that the major products, highly oxygenated organic peroxides, are lost to the chamber walls. In the atmosphere, formation of these compounds may contribute to organic aerosol mass.

Bidentate ligand 8-aminoquinoline-aided Pd-catalyzed diastereoselective β-arylation of the prochiral secondary sp3 C–H bonds of 2-phenylbutanamides and related aliphatic carboxamides

Investigations on the Pd-catalyzed 8-aminoquinoline-aided diastereoselective β-arylation of the prochiral 2° sp3 C–H bonds of various aliphatic carboxamides having substituents at the α- or γ-positions are reported. The Pd-catalyzed β-arylation of the 2° sp3 C–H bonds of racemic 2-phenylbutanamides with aryl iodides gave the arylated products (±)-3a–l (anti isomers) with moderate to good diastereoselectivities (dr up to 86:14). Next, the Pd-catalyzed β-arylation of various γ-substituted aliphatic carboxamides with aryl iodides furnished the corresponding C–H arylated products with poor diastereoselectivities. Then, the arylation of the C(β)-H bonds of 2-ethyl-N-(quinolin-8-yl)butanamide possessing two prochiral centers with aryl iodides successfully furnished the bis arylated products meso-8eA–hA and (±)-8eB–hB (diastereomers). The arylation of (S)-2-phenylbutanamide also gave the corresponding enantiomerically enriched compounds 10a–c (anti isomers). The stereochemistry of the products (±)-3a–l (major isomers), meso-8eA–hA (major isomers), (±)-8eB–hB (minor isomers) and enantiomerically enriched compounds 10a–c (major isomers) were assigned based on the X-ray structures of the major isomers 3b,c,e,l, 8eA, 10c and minor isomers 8eB and 8fB. The limitations and outcome of the stereocontrol in the Pd-catalyzed C–H arylation reactions involving aliphatic carboxamides are illustrated.

Zinc-Mediated Allylation Followed by Lactonization of Dialkyl 2-(3-Oxo-1,3-diarylpropyl)malonates: Construction of δ-Lactones with Multiple Stereocenters

A variety of polysubstituted δ-lactones containing three or four stereocenters were prepared from various dialkyl 2-(3-oxo-1,3-diarylpropyl)malonates by a Barbier-type zinc-mediated allylation or cyclohexenylation of the keto group, followed by intramolecular lactonization/transesterification. The stereochemistry of the major isomers was confirmed by X-ray crystal structure analysis of representative compounds.

Abstract 2826: Equimolar vs. pharmacokinetics-guided dosing in anti-cancer efficacy assessment of precursor-product pairs: Example with pyranocoumarins from Korean Angelica

Abstract Prostate cancer is a malignant disease quite unique to men and has the second highest mortality rate next to lung cancer in the United States, with an estimated 233,000 new cases to be diagnosed in 2014. Angelica gigas Nakai (AGN) is a traditional medicinal herb in Korea and China. Ethanol extract of dried AGN root has been shown by us and others to exert anti-cancer activity in several allograft and xenograft models. In recently completed studies in primary carcinogenesis model (TRAMP mice), our group has demonstrated that AGN ethanol extract can significantly suppress the growth of neuroendocrine (NE)-lineage cancers and inhibit prostate epithelial lineage lesions. These studies also found that major pyranocoumarin isomer compounds decursin (D) and decursinol angelate (DA) from AGN when provided at equimolar intake to that provided by AGN accounted for the epithelial lineage suppression efficacy, but was less active than AGN extract against NE-Ca growth. Because rodent models and humans convert D/DA rapidly and extensively (&amp;gt;95%) into decusinol (DOH), we hypothesize that DOH (and/or its metabolites) may be the true “active” chemical for suppressing the epithelial cancer. To test this, we compared oral gavage of DOH at equimolar dose as D/DA in SCID mice carrying human LNCaP/AR-Luc cells inoculated subcutaneously. Whereas DOH treated mice showed greater suppression of tumor growth than D/DA, measurement of plasma DOH levels showed 1.7 fold higher in the former at 3 h post-dose. Our earlier work has shown in a rat model that gavage of DOH led to 2.4 fold area under curve (AUC) over that achieved by equimolar dosing of D/DA, suggesting differences for absorption, distribution, metabolism, and excretion (ADME) of DOH vs. D/DA in other species as well. We are currently conducting PK studies of DOH and D/DA in mice to establish their PK parameters in order to achieve bio-equivalent dosing to critically test DOH efficacy and our hypothesis. In summary, PK-evaluation of precursor-product pairs might be important to determine bio-equivalent dosing before costly anti-cancer efficacy tests are conducted to ensure valid efficacy comparison. Citation Format: Wei Wu, Manohar Puppala, Suni Tang, Jinhui Zhang, Chengguo Xing, Cheng Jiang, Junxuan Lu. Equimolar vs. pharmacokinetics-guided dosing in anti-cancer efficacy assessment of precursor-product pairs: Example with pyranocoumarins from Korean Angelica. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2826. doi:10.1158/1538-7445.AM2015-2826

Coleifolides A and B, Two New Sesterterpenoids from the Aerial Parts of Scutellaria coleifolia H.Lév.

Coleifolides A and B (1 and 2), two new sesterterpenoids with a β-methyl-α,β-unsaturated-γ-lactone moiety, were isolated from the aerial parts of Scutellaria coleifolia H.Lév. (Lamiaceae), together with three known compounds. Their structures were elucidated by NMR and MS examinations. Coleifolides A and B were concluded to be partially racemic compounds by the HPLC analysis using a chiral column or introduction of chiral derivatizing agents. The absolute configuration of the major isomer was determined by analyses of the CD spectrum as well as NMR data of (R)- and (S)-2-NMA derivatives. Coleifolides A and B are structurally similar to manoalide derivatives, previously isolated from marine sponges, and appear to be the first examples of this type of compounds being isolated from higher plants.

Synthesis and structures of dinuclear RhIII and IrIII complexes supported by a tetraphosphine, meso- or rac-bis{[(diphenylphosphinomethyl)phenyl]phosphino]}methane

Reactions of [Cp*MCl2]2 with meso- or rac-dpmppm in the presence of NH4PF6 afforded mixtures of stereoisomers formulated as [(Cp*MCl)2(meso- or rac-dpmppm)](PF6)2, from which the major isomers, rac-M2-[(Cp*MCl)2(meso-dpmppm)](PF6)2 (M = Rh (1a), Ir (1b)) and rac-M2-[(Cp*MCl)2(rac-dpmppm)](PF6)2 (M = Rh (2a), Ir (2b)), were isolated and characterized by IR, UV–vis, ESI mass, and 1H and 31P{1H} NMR spectroscopy and X-ray crystallography, where dpmppm is bis{[(diphenylphosphinomethyl)phenyl]phosphino}methane and Cp* is η5-pentamethylcyclopentadienyl. The isomeric tetraphosphine incorporates two {Cp*MCl} fragments with four-membered chelation through a pair of outer and inner phosphine units, and fixes them ca. 6.9 Å apart from each other. The configurations around the metal centers in 2 were determined to avoid repulsive interaction between the phenyl group on the inner P atom and the M-bound chloride anion, while those in 1 would be determined by minimizing not only the Ph/Cl repulsion but also repulsion between the two metal fragments. In the dichloromethane solutions, the major isomers 1 and 2 were not converted to any other minor isomers even at high temperature, but in dmf and dmso, only 1a was readily transformed into the minor isomer, meso-M2-[(Cp*RhCl)2(meso-dpmppm)](PF6)2. Cyclic voltammograms of 1a,b and 2a,b demonstrated two irreversible 2e− reduction waves corresponding to MIIIMIII → MIMIII → MIMI, in which the mixed-valence states with meso-dpmppm could be stabilized to a larger extent than with rac-dpmppm. Complex 1a heated in acetonitrile with AgOTf/NH4OTf afforded a Rh2Ag2 mixed-metal complex, [(Cp*Rh(CH3CN))2Ag2(OTf)2(meso-dpmppm)2](OTf)4 (5).

Cobalt(III) Complexes of D‐Galactosylamine

AbstractThe β‐pyranose isomer of D‐galactosylamine (1) formed complexes with three different cobalt(III) fragments. Crystals containing the dication [Co(tren)(β‐D‐Galp1N2H–1‐κ2N1,O2)]2+ (3) showed coordination through the anomeric amino group (N1) and the deprotonated hydroxy group (O2) of the 4C1 β‐pyranose form, which is also the major isomer of free galactosylamine. The cationic complexes [Co(fac‐dien)(β‐D‐Galp1N2H–1‐κ2N1,O2)]2+ (4) and [Co(phen)2(β‐D‐Galp1N2H–1‐κ2N1,O2)]2+ (5) were analysed by NMR spectroscopy and showed the same coordination mode as 3. In terms of available ligand isomers it was shown that 1 exhibits an anomeric equilibrium in solution of both pyranose and both furanose forms as is typical for the parent glycose, galactose.

ChemInform Abstract: Tandem Stereoselective Synthesis of New Trifluoromethylated Pyranopyrazoles.

Abstract An efficient tandem Michael addition/aromatization/cyclization reaction of pyrazolones with α,β-unsaturated trifluoromethyl ketones is described. The notable features of this tandem process are its operational simplicity, easily accessible starting materials, and mild reaction conditions. The corresponding trifluoromethylated pyranopyrazoles were obtained in excellent yields (85–99%) with good to excellent diastereoselectivities (6:1–30:1). In addition, the stereochemical assignment of the major isomer by X-ray crystallographic analysis indicated that the trans-products were predominantly formed.

C2-Symmetric 1,2-di(fluorenylidene)cyclobutanes: syntheses, structures, rearrangements and reactivity

Attempted deprotonation of 1,2-di(fluorenylidene)cyclobutane, 8, using n-butyl or tert-butyl-lithium led instead to 1,4-addition across the 1,3-butadiene unit to yield the 1-(9H-fluorenyl-2-(9-butyl-9H-fluorenyl)cyclobutene 10 or 11, respectively; analogously, n-butyl-lithium and trans-3,4-bis(trimethylsilyl)-1,2-di(fluorenylidene)cyclobutane, 12, furnished the corresponding 1,4-adduct 13. Bromination of 8 with N-bromosuccinimide led to mono-, di- and tri-bromo derivatives whereby, in the trans-di-bromo systems, the helical character of the trans bromines could either match (in 16) or oppose (in 17) the helicity of the fluorenylidenes. In accordance with DFT calculations, the diastereomer 17 is the favoured product, and a pure sample of 16 in solution underwent equilibration via cleavage of the C(3)–C(4) linkage such that 17 became the major isomer. Attempted addition of bromine to 3,4-di(fluorenylidene)-1,2-diphenylcyclobutene, 24, unexpectedly yielded the diketone 2,3-di(9H-fluoren-9-ylidene)-1,4-diphenylbutane-1,4-dione, 25. The structures of 10, 11, 13, 16, 17 and 25 were determined by X-ray crystallography.

Synthesis, Characterization, and Some Properties of Cp*W(NO)(H)(η(3)-allyl) Complexes.

Sequential treatment at low temperatures of Cp*W(NO)Cl2 in THF with 1 equiv of a binary magnesium allyl reagent, followed by an excess of LiBH4, affords three new Cp*W(NO)(H)(η(3)-allyl) complexes, namely, Cp*W(NO)(H)(η(3)-CH2CHCMe2) (1), Cp*W(NO)(H)(η(3)-CH2CHCHPh) (2), and Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3). Complexes 1-3 are isolable as air-stable, analytically pure yellow solids in good to moderate yields by chromatography or fractional crystallization. In solutions, complex 1 exists as two coordination isomers in an 83:17 ratio differing with respect to the endo/exo orientation of the allyl ligand. In contrast, complexes 2 and 3 each exist as four coordination isomers, all differing by the orientation of their allyl ligands which can have either an endo or an exo orientation with the phenyl or methyl groups being either proximal or distal to the nitrosyl ligand. A DFT computational analysis using the major isomer of Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3a) as the model complex has revealed that its lowest-energy thermal-decomposition pathway involves the intramolecular isomerization of 3a to the 16e η(2)-alkene complex, Cp*W(NO)(η(2)-CH2═CHCH2Me). Such η(2)-alkene complexes are isolable as their 18e PMe3 adducts when compounds 1-3 are thermolyzed in neat PMe3, the other organometallic products formed during these thermolyses being Cp*W(NO)(PMe3)2 (5) and, occasionally, Cp*W(NO)(H)(η(1)-allyl)(PMe3). All new complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them have been established by single-crystal X-ray crystallographic analyses.

Modulation of inflammation and immunity by dietary conjugated linoleic acid

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid. This family of polyunsaturated fatty acids has drawn significant attention in the last three decades for its variety of biologically beneficial properties and health effects. CLA has been shown to exert various potent protective functions such as anti-inflammatory, anticarcinogenic, antiadipogenic, antidiabetic and antihypertensive properties in animal models of disease. Therefore, CLA represents a nutritional avenue to prevent lifestyle diseases or metabolic syndrome. Initially, the overall effects of CLA were thought to be the result of interactions between its two major isomers: cis-9, trans-11 and trans-10, cis-12. However, later evidence suggests that such physiological effects of CLA might be different between the isomers: t-10, c-12-CLA is thought to be anticarcinogenic, antiobesity and antidiabetic, whereas c-9, t-11-CLA is mainly anti-inflammatory. Although preclinical data support a benefit of CLA supplementation, human clinical findings have yet to show definitive evidence of a positive effect. The purpose of this review is to comprehensively summarize the mechanisms of action and anti-inflammatory properties of dietary CLA supplementation and evaluate the potential uses of CLA in human health and disease.

Phosphine Oxide Catalyzed, Tetrachlorosilane-Mediated Enantioselective Direct Aldol Reactions of Thioesters

The stereoselective direct aldol reaction of S-phenyl thioesters and aromatic aldehydes promoted by tetrachlorosilane was realized for the first time; the proposed mechanism involves the formation of a chiral cationic hypervalent silicon species and requires the presence of catalytic amounts of a Lewis base, like a chiral phosphine oxide. The reaction affords syn β-hydroxy thioesters as major isomers in good yields, high diastereoselectivity (up to 99:1), and up to 92% enantiomeric excess. The absolute configuration of the major isomer was established by converting the product into the corresponding β-hydroxy ester. The scope of the reaction was also investigated by employing differently substituted thioesters in combination with different aromatic aldehydes.

Phosphine-Catalyzed Diastereoselective Synthesis of β-Lactones from Disubstituted Ketenes and α-Chiral Oxyaldehydes.

In this article we describe a catalytic procedure for the diastereoselective synthesis of β-lactones bearing two stereogenic centers, from disubstituted ketenes and α-chiral oxyaldehydes. Tri-n-butylphosphine was found to be the optimal catalyst in terms of effecting both good yield and diastereoselectivity (dr from 3:1 to 32:1 for 8 examples) in β-lactone formation. The major isomer of the β-lactone products was determined to be the anti-diastereomer, and its formation was rationalized by a polar Felkin-Anh model. Involvement of phosphonium enolate intermediates in the reaction mechanism was indicated through reaction monitoring by (31)P NMR spectroscopy. The utility of the methodology is demonstrated by a short synthesis of a (+)-peloruside A synthon.