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A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological profile are presented as potential antipsychotics. The in vitro pharmacological profile includes D2 partial agonism (30–55%), 5-HT1A partial agonism (60–90%), and 5-HT2A antagonism. Selected compounds in this series displayed good in vivo activity and potency.

The total synthesis of the spiroketal ionophore antibiotic routiennocin 1 (CP-61,405) employing π-allyltricarbonyl iron lactone complexes is described. These complexes were used as precursors for the preparation of substituted 2-phenylsulphonyl pyrans which, in turn, were coupled with iodoacetonides to afford spiroketals. Elaboration of the spiroketals by tetra- n -propylammonium perruthenate (TPAP) oxidation and coupling with 2-lithio-1-[β-(trimethylsilyl)ethoxymethyl] pyrrole followed by further oxidation, deprotection, oxidation and benzoxazole formation afforded the natural product. The preparation of the amino phenol fragment necessary for benzoxazole formation involved a novel amination procedure using benzeneselenenic anhydride and hexamethyldisilazane followed by samarium diiodide reduction.

A new surface chemistry presenting an abundance of functional groups for ligand immobilization in an ultra-low fouling background all in one material for nanoparticles was introduced. This surface platform, as demonstrated by zwitterionic poly(carboxybetaine acrylamide) (polyCBAA) coated nanoparticles, is not only ultra stable in undiluted human blood serum, but also can be conjugated to biomolecules conveniently and effectively. Thus, this surface chemistry is ideal to create multi-functional nanoparticles for targeted delivery and diagnostics. In addition, this work clearly shows that 10% blood serum commonly used to evaluate the stability of nanoparticles is insufficient and a new evaluation criterion with undiluted blood serum is recommended.

A highly convergent total synthesis of the anthelmintic macrolide avermectin B1a 1 is described. The key features of this synthesis include the introduction of the C(11)–C(15) portion by selective ring opening of a symmetrical 1,4-bis-epoxide 4 followed by reaction with the anion derived from the 3-methyl-2-(1-methylpropyl)-6-phenylsulphonylpyran 3 to afford the ‘northern’ C(11)–C(25) fragment 39. Coupling of the derived C(11)–C(25) aldehyde unit 42 with a C(1)–C(10)‘southern’ fragment 2 was achieved via a novel deconjugative vinyl sulphone anion sequence. Macrolactonisation and subsequent introduction of the 3,4-double bond gave the aglycone portion 51. The oleandrosyloleandrose disaccharide was introduced by a novel silver-mediated coupling between the 5-acetylated aglycone 70 and the thiocarbonylimidazolide 69. Final deacetylation was accomplished using Super-Hydride to give the natural product 1.

Processes for the synthesis of fluorinated 1,8-naphthyridinone derivatives including 6,7-difluoro-1,8-naphthyridin-2-one are described.

Purpose In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Methods Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Results Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely stained for PMCA, whereas the larger cone pedicles preferentially stained for NCX1 at their active zones and PMCA near their mitochondria. EM and ET revealed that mitochondria in rod spherules and cone pedicles differed markedly in their number, location, size, volume, and total cristae surface area, and cristae junction diameter. Rod spherules had one large ovoid mitochondrion located near its active zone, whereas cone pedicles averaged five medium-sized mitochondria clustered far from their active zones. Most spherules had one ribbon synapse, whereas pedicles contained numerous ribbon synapses. Fluo-3 imaging studies revealed that during darkness rod spherules maintained a lower [Ca2+] than cone pedicles, whereas during light adaptation pedicles rapidly lowered their [Ca2+] below that observed in spherules. Conclusions These findings indicate that ATP demand and mitochondrial ATP production are greater in cone pedicles than rod spherules. Rod spherules employ high affinity/low turnover PMCA and their mitochondrion to maintain a relatively low [Ca2+] in darkness, which increases their sensitivity and signal-to-noise ratio. In contrast, cone pedicles utilize low affinity/high turnover NCX to rapidly lower their high [Ca2+] during light adaptation, which increases their response kinetics. Spatiotemporal fluo-3-Ca2+ imaging results support our immunocytochemical results. The clustering of cone pedicle mitochondria likely provides increased protection from Ca2+ overload and permeability transition. In summary, these novel studies reveal that several integrated cellular and subcellular components interact to regulate ATP and Ca2+ dynamics in rod and cone synaptic terminals. These results should provide a greater understanding of in vivo photoreceptor synaptic terminal exocytosis/endocytosis, Ca2+ overload and therapies for retinal degenerations.

[7705-08-0] Cl3Fe (MW 162.20) InChI = 1S/3ClH.Fe/h3*1H;/q;;;+3/p-3 InChIKey = RBTARNINKXHZNM-UHFFFAOYSA-K (mild oxidant capable of phenolic coupling,1 dimerizing aryllithiums6 and ketone enolates;7, 8 mild Lewis acid: catalyzes ene reactions,21 Nazarov cyclizations,18-20 Michael additions,24 and acetonations29) Alternate Name: ferric chloride. Physical Data: mp 306 °C; d 2.898 g cm−3.25 Solubility: 74.4 g/100 mL cold water, 535.7 g mL−3 boiling water; v sol alcohol, MeOH, ether, 63 g mL−1 in acetone (18 °C). Form Supplied in: black crystalline powder; widely available. Preparative Methods: anhydrous FeCl3 available commercially is adequate for most purposes. However, the anhydrous material can be obtained from the hydrate by drying with thionyl chloride7 or azeotropic distillation with benzene.12 Handling, Storage, and Precautions: is hygroscopic and corrosive; inhalation or ingestion may be fatal. It causes eye and skin irritation. It should be stored and handled under an inert dry atmosphere.36 Use in a fume hood.

(FeCl3) [7705-08-0] Cl3Fe (MW 162.20) InChI = 1S/3ClH.Fe/h3*1H;/q;;;+3/p-3 InChIKey = RBTARNINKXHZNM-UHFFFAOYSA-K (NaH) [7646-69-7] HNa (MW 24.00) InChI = 1S/Na.H InChIKey = MPMYQQHEHYDOCL-UHFFFAOYSA-N (mild reduction of aldehydes and ketones to alcohols;2 reduction of alkenes and alkynes3) Alternate Name: ferric chloride–sodium hydride. Preparative Method: generated in situ via addition of a solution of Iron(III) Chloride (14 mg equiv) in THF (20 mL) to a suspension of Sodium Hydride (42 mg equiv) in THF (5 mL). The yellow suspension is stirred at rt for 4 h under argon. A solution of the carbonyl compound (2 mmol) in THF (2 mL) is added and stirring continued at rt. Handling, Storage, and Precautions: FeCl3 is hygroscopic and corrosive; inhalation or ingestion may be fatal. NaH is a flammable solid which reacts violently with water. The powder ignites spontaneously in air. It should be handled in an inert dry atmosphere. Use in a fume hood.

[14215-32-8] FeN9 (MW 181.94) InChI = 1S/Fe.3N3/c;3*1-3-2/q+3;3*-1 InChIKey = MKNZTJIHKCVUHC-UHFFFAOYSA-N (preparation of azidoalkanes1) Alternate Name: ferric azide. Form Supplied in: made in situ. Preparative Methods: the reagent is prepared and used in situ1 by addition of Sodium Azide (15 mmol) and Iron(III) Sulfate (7.5 mmol) in methanol (20 mL) to the organoborane (5 mmol) stirred at rt for 30 min under nitrogen. The mixture is then cooled to 0 °C and 30% Hydrogen Peroxide added via a syringe pump (0.1 mL min−1). Slow addition of hydrogen peroxide increases yields. Handling, Storage, and Precautions: is poisonous by ingestion or skin contact. It is an unstable explosive, sensitive to impact. Decomposition yields toxic fumes of NOx and Na2O. Organic azides are sensitized by metal salts or traces of strong acid.8 Fe2(SO4)3 is harmful if swallowed or inhaled. It causes eye and skin irritation. Use in a fume hood.

(FeCl3) [7705-08-0] Cl3Fe (MW 162.20) InChI = 1S/3ClH.Fe/h3*1H;/q;;;+3/p-3 InChIKey = RBTARNINKXHZNM-UHFFFAOYSA-K (Ac2O) [108-27-7] C4H6O3 (MW 102.10) InChI = 1S/C4H6O3/c1-3(5)7-4(2)6/h1-2H3 InChIKey = WFDIJRYMOXRFFG-UHFFFAOYSA-N (Lewis acid cleaving ethers,2 gem-diacetates,8 imides11) Alternate Name: ferric chloride–acetic anhydride. Preparative Method: this reagent combination is used in situ via addition of anhydrous Iron(III) Chloride (6.2 mmol), to the substrate (35.5 mmol) and Acetic Anhydride (15 mL).2 Handling, Storage, and Precautions: reactions can be mildly exothermic. FeCl3 is hygroscopic and corrosive, inhalation or ingestion may be fatal. Acetic anhydride is moderately toxic by inhalation, ingestion, and skin contact. It is a skin and severe eye irritant. It can react vigorously with oxidizing agents, and will react vigorously with water.12 Use in a fume hood.

[36654-49-6] C9H21Cl6Fe2N3O3 (MW 543.73) InChI = 1S/3C3H7NO.6ClH.2Fe/c3*1-4(2)3-5;;;;;;;;/h3*3H,1-2H3;6*1H;;/q;;;;;;;;;2*+3/p-6 InChIKey = QTEBKOLYZLVSKQ-UHFFFAOYSA-H (mild oxidant; oxidative coupling2 of phenols, ketone enolates,3 and allylic sulfones;4 ring expansion of silyloxybicyclo[n.1.0]alkanes;5 oxidative decomplexation of chromium carbonyl complexes6) Alternate Name: ferric chloride–DMF. Physical Data: mp 220 °C. Preparative Method: N,N-Dimethylformamide (1.5 mol) is added with stirring to a solution of Iron(III) Chloride (1 mol) in dry ether (1.6 L) to yield a precipitate which is filtered and dried in vacuo to yield a yellowish green powder (95%) which is sufficiently pure to use for oxidation reactions.2 Purification: recrystallize from dichloromethane and ethanol to give needles. Handling, Storage, and Precautions: stable to air and moisture; FeCl3 is hygroscopic and corrosive; inhalation or ingestion may be fatal; DMF is mildly toxic by skin contact and inhalation; it is a skin and eye irritant. Use in a fume hood.

(FeCl3) [7705-08-0] Cl3Fe (MW 162.20) InChI = 1S/3ClH.Fe/h3*1H;/q;;;+3/p-3 InChIKey = RBTARNINKXHZNM-UHFFFAOYSA-K (Al2O3) [1344-28-1] Al2O3 (MW 101.96) InChI = 1S/2Al.3O InChIKey = TWNQGVIAIRXVLR-UHFFFAOYSA-N (proton scavenger; mild Lewis acid catalyst for ene reactions1, 2) Alternate Name: ferric chloride–alumina. Form Supplied in: the individual reagents are commercially available. Preparative Method: anhydrous Iron(III) Chloride (62 mmol) is added to anhydrous CH2Cl2 (160 mL) under argon. The mixture is stirred vigorously while 50 g chromatography grade basic Alumina is added in small portions under argon. Stirring is continued for 1 h to obtain homogeneous adsorbtion and the solvent is then removed under reduced pressure. The basic alumina supported FeCl3 obtained can be stored under argon for several months without loss of catalytic activity. Handling, Storage, and Precautions: should be stored and manipulated in an inert, dry atmosphere; FeCl3 is hygroscopic and corrosive, inhalation or ingestion may be fatal; basic alumina is an irritant. Use in a fume hood.

(Fe(acac)3) [14024-18-1] C15H21FeO6 (MW 353.21) InChI = 1S/3C5H8O2.Fe/c3*1-4(6)3-5(2)7;/h3*3,6H,1-2H3;/q;;;+3/p-3/b3*4-3-; InChIKey = AQBLLJNPHDIAPN-LNTINUHCSA-K (H2O2) [7722-84-1] H2O2 (MW 34.02) InChI = 1S/H2O2/c1-2/h1-2H InChIKey = MHAJPDPJQMAIIY-UHFFFAOYSA-N (β-epoxidation of cholesterol derivatives;2 trans-epoxidation of alkenes3) Alternate Name: tris(acetylacetonate)iron(III)–hydrogen peroxide. Physical Data: Fe(acac)3: mp 184 °C, d 1.33 g cm−3. Solubility: slightly sol cold and hot water; sol alcohol, acetone, benzene, chloroform. Form Supplied in: dark red powder; widely available. Preparative Method: reagent combination is generated in situ, via dropwise addition of 30% Hydrogen Peroxide (49 mmol) to a stirred solution of Tris(acetylacetonato)iron(III) (2.7 mmol), and substrate (0.26 mmol) in acetonitrile.2, 3 Handling, Storage, and Precautions: use in a fume hood. Fe(acac)3 causes severe eye irritation and may cause skin irritation. Toxic fumes of carbon monoxide and carbon dioxide are generated on decomposition. It is incompatible with strong oxidizing agents; thus the H2O2 has to be used in excess because it is decomposed by FeIII ion.4 Reactions should be worked up by decomposition of excess H2O2 with saturated aqueous sodium sulfite and then extraction of product with ether. See also Hydrogen Peroxide.

(FeCl3) [7705-08-0] Cl3Fe (MW 162.20) InChI = 1S/3ClH.Fe/h3*1H;/q;;;+3/p-3 InChIKey = RBTARNINKXHZNM-UHFFFAOYSA-K (SiO2) [112926-00-8] O2Si (MW 60.09) InChI = 1S/O2Si/c1-3-2 InChIKey = VYPSYNLAJGMNEJ-UHFFFAOYSA-N (Lewis acid; dehydration;2 acetal cleavage;3, 4 rearrangements;2, 6, 7 thioacetalization;9 mild oxidant; oxidative cyclizations10-13) Alternate Name: ferric chloride–silica gel. Form Supplied in: pale yellow powder, 5% wt on silica gel; commercially available. Preparative Methods: several procedures have been reported for preparation of this reagent depending on the synthetic transformation required. The two procedures described below have been used for cleavage of acetals.1, 2 Silica gel (10 g, 70–230 mesh) is added to a solution of FeCl3·6H2O (1.2 g) in acetone at rt. The solvent is removed on a rotary evaporator and the mixture then heated in vacuo at 60 °C for 30 min/0.1 mmHg to yield a yellow powder.1 Anhydrous FeCl3 (4 g) and chromatography grade silica gel (50 g 70–230 mesh) are stirred together in the absence of solvent at rt for 24 h to achieve homogeneous adsorption. A pale yellowish green powder is obtained.2 Handling, Storage, and Precautions: the material obtained by procedure 1 is moisture- and light-sensitive, but can be stored for extended periods under dry nitrogen at rt in a brown bottle. The material obtained in procedure 2 is used immediately. FeCl3 is hygroscopic and corrosive; inhalation or ingestion may be fatal. Silica gel is an irritant. Use in a fume hood.

[4119-52-2] C3FeN3S3 (MW 230.12) InChI = 1S/3CHNS.Fe/c3*2-1-3;/h3*3H;/q;;;+3/p-3 InChIKey = SUBFIBLJQMMKBK-UHFFFAOYSA-K (reacts with trialkylboranes to give alkyl thiocyanates;2 thiocyanation of unsaturated acids and esters7) Alternate Name: ferric thiocyanate. Solubility: very sol water; dec in hot water; sol alcohol, ether, acetone. Preparative Method: the reagent is prepared and used in situ, via dropwise addition of a mixture of iron(III) ammonium sulfate (6 equiv) and potassium thiocyanate (18 equiv) in water to a solution of organoborane in THF. The mixture is refluxed for 24 h. The products are obtained via extraction with petroleum ether several times and distillation.2 Handling, Storage, and Precautions: metal thiocyanates on heating to decomposition, or on contact with acid or acid fumes, emit highly toxic fumes. Organic thiocyanates have low acute toxicity, but prolonged absorption may produce skin eruptions, running nose, nausea, and vomiting. Violent reactions have occurred with strong oxidizers.8 Use in a fume hood.

(FeSO4·7H2O) [7720-78-7] H14FeO11S (MW 278.06) InChI = 1S/Fe.H2O4S.7H2O/c;1-5(2,3)4;;;;;;;/h;(H2,1,2,3,4);7*1H2/q+2;;;;;;;;/p-2 InChIKey = SURQXAFEQWPFPV-UHFFFAOYSA-L (O2) [7782-44-7] O2 (MW 32.00) InChI = 1S/O2/c1-2 InChIKey = MYMOFIZGZYHOMD-UHFFFAOYSA-N (selective oxidant for 15-hydroxylation of steroids,1 direct hydroxylation of aromatic and aliphatic substrates7, 8) Alternate Name: ferrous sulfate–oxygen. Preparative Methods: the reagent combination is generated in situ via dropwise addition of an aqueous solution (500 mL) of Iron(II) Sulfate (15 g, 54 mmol) to a stirred buffer (0.1 M Na2HPO4, pH 6.8, 2.5 L) solution of substrate (2.25 mmol) under bubbling oxygen at 70 °C. Room temperature may be adequate for some substrates. Handling, Storage, and Precautions: is air and moisture sensitive; keep in a tightly closed container; incompatible with strong oxidizing agents; irritant; ingestion may be lethal.

A series of diaryl-substituted heterocyclic ureas was prepared, and their ability to inhibit acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in cholesterol-fed animal models in vivo was examined. N-(2,6-Diisopropylphenyl)-N'-tetrazole or isoxazole-substituted heterocyclic ureas proved optimal. A carbon chain of 11-14 carbons substituted 1,3 with respect to the amine provided the optimal side chain. Substitution of the alkyl chain generally lowered activity. Tetrazole urea 2i dosed at 3 mg/kg lowered plasma total cholesterol (TC) 67% in an acute, cholesterol-fed (C-fed) rat model of hypercholesterolemia and 47% in C-fed dogs. Tetrazole 2i, dosed at 10 mg/kg, also lowered TC 52% and raised HDL cholesterol 113% in rats with pre-established hypercholesterolemia.

A series of heterocyclic amides were synthesized and evaluated as inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and for cholesterol lowering in cholesterol-fed rats. Compounds were evaluated for cell-based macrophage ACAT inhibition, bioactivity, and adrenal toxicity. Candidates were selected for evaluation in cholesterol-fed dogs and, ultimately, the injured cholesterol-fed rabbit model of atherosclerosis. The heterocyclic amides potently inhibited rabbit liver ACAT (IC50's = 0.014-0.11 microM), and the majority of compounds significantly lowered plasma cholesterol (42-68%) in an acute cholesterol-fed rat model at 3 mg/kg. The most efficacious compounds in the rat were evaluated for bioactivity in vivo and arterial ACAT inhibition in a cell-based macrophage ACAT assay. Two highly bioactive analogs, (+/-)-2-(3-dodecylisoxazol-5-yl)-2-phenyl-N-(2,4,6-trimethoxypheny l) acetamide (13a) and (+/-)-2-(5-dodecylisoxazol-3-yl)-2-phenyl-N-(2,4,6-trimethoxypheny l) acetamide (16a), were selected for further study and were found to be nontoxic in a guinea pig model of adrenal toxicity. Compounds 13a and 16a lowered total cholesterol in the cholesterol-fed rat, rabbit, and dog models of pre-established hypercholesterolemia. Compound 13a in the injured cholesterol-fed rabbit model of atherosclerosis was effective in slowing the development of cholesteryl ester-rich thoracic aortic lesions, reducing lesion coverage by 53% at a dose of 1 mg/kg.

The interactions which govern chemical processes may be broadly categorized into specific interactions, high activity for a certain target molecule, and nonspecific interactions, low activity for all targets. Despite their ubiquity in biology and chemistry, nonspecific interactions are generally overlooked and a fundamental understanding of nonspecific interactions is lacking. Molecular chaperones are large protein complexes which have evolved to resist nonspecific interactions. Their interior surface resists binding to thousands of types of misfolded proteins. Proteins found in the cytoplasm, a crowded environment with many spurious binding targets, are another example. These proteins have evolved high selectivity and stability despite nonspecific interactions. Using structural bioinformatics, we have studied the interiors of molecular chaperones from five species and examined the surface chemistry of 1162 proteins, categorized by if they are present in the cytoplasm or extracellular space. A better understanding of how nature resists nonspecific interactions is key for the chemistry of materials, surfaces, and particles which must remain stable in complex environments. The abundance of amino acids, their interactions, their hydration, and sequence patterns were compared in these two systems, molecular chaperones and proteins surfaces. Striking similarities were found and trends were identified as the system environments became harsher. Peptide based mimics were synthesized to test the conclusions. This, in turn, has led to the design of new stealth compounds and a deeper understanding of nonspecific interactions.

The presence of plasma cholesteryl ester transfer protein (CETP) activity may be atherogenic, and, therefore, strategies to inhibit its activity or production may result in a beneficial effect on lipoprotein profiles and the disease process. The current report describes 4-phenyl-5-tridecyl-4H-1,2,4- triazole-3-thiol (PD 140195), a novel CETP inhibitor. The concentration-dependent inhibition of CETP by PD 140195 and the inhibitory monoclonal antibody (Mab) TP2 is demonstrated in a variety of in vitro assay systems. Molecular models of PD 140195 suggest a spatial mimicry of the cholesteryl ester structure. Despite the structural similarity, kinetic studies with a fluorescent cholesteryl ester analog suggest that the inhibition of transfer is not competitive. PD 140195 also selectively inhibited cholesteryl ester but not triglyceride transfer, while the Mab TP2 blocked CETP transfer of both. Studies were carried out to determine whether CETP inhibition observed in vitro could also be demonstrated in vivo. When PD 140195 was intravenously infused to anesthetized rabbits (up to 20 mg/kg), only transient CETP inhibition was observed. In vitro reconstitution studies in the presence of bovine serum albumin resulted in marked reduction of PD 140195 inhibitory activity. Thus, the low activity of PD 140195 in whole plasma probably results from binding to other plasma proteins.

In the present report we describe a simple and practical method to assess CETP activity in a defined system by use of microemulsions containing a fluorescent cholesteryl ester analog. The microemulsions are stable, simple to prepare, and can be made to defined composition. Initial transfer rates are easily determined by monitoring changes in fluorescence. We have used the fluorescent cholesteryl ester analog, cholesteryl 4,4-difluoro-5,7-dimethyl-4-boro-3 alpha, 4 alpha-diaza-3-indacenedodecanoate (BODIPY-CE), to demonstrate the utility of this assay. The assay takes advantage of the concentration-dependent self-quenching of BODIPY-CE, when this analog is incorporated into microemulsions. We have used this new assay to demonstrate fluorescent lipid transfer facilitated by rabbit and human d > 1.21 g/ml plasma fraction and recombinant human CETP. A known inhibitory monoclonal antibody (Mab) to human CETP blocked BODIPY-CE transfer in a dose-dependent manner. We have also used BODIPY-CE microemulsions to measure CETP activity in whole plasma.

Hypercholesterolemia is one of the few independent risk factors definitively linked to increased morbidity and mortality due to myocardial infarction. One possible therapy of current interest is the prevention of the absorption of dietary cholesterol by inhibiting the enzyme, acyl-CoA: cholesterol acyltransferase (ACAT), which catalyses the intracellular formation of cholesterol esters. Evidence is now accumulating that suggests that ACAT inhibition may not only lower plasma cholesterol levels, but may also have a direct effect at the artery wall, where ACAT has been shown to be responsible for the accumulation of cholesterol esters in arterial lesions. Drago Sliskovic and Andrew White discuss the importance of ACAT in the lipid transport system and the consequences of its inhibition in a variety of tissues, with emphasis on both lipid-lowering and anti-atherosclerotic effects.

The osmium(VII) salt (Ph4P)[OsO4] functions as a stoichiometric oxidant for benzylic and allylic alcohols, oxidising primary alcohols to aldehydes and secondary alcohols to ketones. Its vibrational spectra and cyclic voltammetric behaviour are compared with those of the perruthenate ion, [RuO4]−.

Tetra-n-butylammonium per-ruthenate (Bun4N)(RuO4) and tetra-n-propylammonium per-ruthenate (Prn4N)(RuO4), with N-methylmorpholine N-oxide, function as mild catalytic oxidants for the high yield conversion of alcohols to aldehydes and ketones and are competitive with more conventional reagents.

Reaction of [OsO3(NR)][R = But, t-pentyl, adamant-1-yl (Ad), or 1,1,3,3-tetramethylbutyl (C8H17)] and of [OsO2(NBut)2] with alkenes R′ yields alkanolaminato and diaminato complexes of stoicheiometries [{OsO2(OR′NR)}2] and [OsO2(NButR′NBut)] respectively. The adducts [OsO3(NR)L](R = But, t-pentyl, or C8H17; L = quinuclidine) and [{OsO3(NR)}2L′]{R = But or C8H17, L′= 1,4-diazabicyclo[2.2.2]octane (dabo) or 1,3,5,7-tetra-azatricyclo[3.3.1.13.7]decane; R = t-pentyl, L′= dabo} react with alkenes R′ to give [OsO2(OR′NR)L] and [{OsO2(OR′NR)}2L′]. The structures of these complexes are discussed.

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