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5-Amino-3-methyl-1-phenyl-1H-pyrazole was prepared to react with various aromatic aldehydes and pyruvic acid to afford 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carbxylic acids. The prepared compounds were characterized by Mass, IR, 1H, 13C NMR spectra and CHN analysis data. Various 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carbxylic acids synthesized during this work were also evaluated for their antibacterial activities. Some of these compounds were found to be good antibacterial agents.

The acylative dimerisation of 2-alkenyl-1,3-thiazolines 1 gives compounds 3 and 8 upon treatment with trichloroacetyl chloride and trifluoroacetic anhydride, respectively. This reaction is completely diastereoselective, in particular giving only a single double-bond isomer. The scope of the reaction has been evaluated synthetically, while a computational study has elucidated the mechanism of the reaction and the origin of stereocontrol. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Crystal structural studies of two new biisoquinoline derivatives, a neutral compound C20H24N2 (3) and a salt C18H21N2 +sdotC10H14BrO4S– sdotH2O (4) are described and discussed. Compound 3 crystallizes in the monoclinic space group P2 1/c, with a = 11.039(2), b = 7.791(2), c = 19.001(4) A, beta = 104.31(3)°, and Z = 4. Compound 4 crystallizes in the monoclinic space group P2 1, with a = 12.0021(3), b = 8.9189(2), c = 12.8685(4) A, beta = 100.7600(10)°, and Z = 2. The absolute stereochemistry of 4 in the solid state has been determined. The biisoquinoline rings in both compounds adopt twist-boat conformations with significant deviations from ideal geometry. The two heterocyclic rings in each species are oriented so that they are not overlayed with each other and the phenyl rings are oppositely directed. The cations and the anions in 4 are linked together through an elaborate system of hydrogen bonding involving the water molecule.

A six-year-old rottweiler presented with a non-septic bile peritonitis caused by projectile trauma. An air gun pellet/projectile had penetrated both walls of the gall bladder leading to bile leakage. A cholecystectomy was performed and the patient made a full recovery.

A new approach to the synthesis of fragments related to the batzelladine alkaloids has been developed using a formal asymmetric aza-Diels–Alder reaction.

Treating 1-bromo-3-chloropropene (II) with tBuLi leads to the formation of unstable 3-chloro-1-lithiopropene which is trapped in situ by alkylboronic esters.

Diastereomerically pure oxazolo[3,2-c]pyrimidines can be readily prepared by the reaction of alkenyloxazolines with isocyanates. The mechanism of this transformation has been investigated computationally. These compounds undergo epimerisation upon prolonged heating, a reaction which is consistent with the proposed stepwise mechanism. Hydrolysis reactions of these compounds have been investigated.

Chiral, enantiomerically pure Pd-catalysts were used to control the regioselectivity of nucleophilic attack in allylic substitutions with optically active 1,3-disubstituted allyl acetates (Schemes 4 – 6). In contrast to reactions with achiral catalysts, where the regioselectivity is determined by the steric and electronic effects of the allylic substituents, chiral catalysts allow selective preparation of either one of the two regioisomeric products, depending on which enantiomer of the catalyst is employed. It is not necessary to start from an enantiomerically pure substrate, because the major and minor enantiomers are converted to different regioisomers (not to enantiomeric products; see Scheme 3), resulting in products of very high ee, even when the starting material is only of moderate enantiomer purity.

The reactions of alkylidenepyrrolidines with α-chlorooximes give isoxazoles via an acylation reaction followed by ring isomerisation. In contrast, and in line with a previous report, the corresponding α-chlorohydrazones give the simple acylation products, although in one instance a cycloadduct was also obtained.

The reaction of alkylidenepyrrolidines with nitrolic acids gives rise to the formation of novel 3,7a-disubstituted (1,2,4-oxadiazol-5-yl)-5,6,7,7a-tetrahydropyrrolo[1,2-d][1,2,4]oxadiazoles. A plausible mechanism for this reaction is proposed, which features nitrosation of the enamine by the nitrous acid that is liberated from the nitrolic acid.

Chiral 2-alkenyloxazolines and 2-alkenylthiazolines react with isocyanates and ketenes to give formal hetero-Diels-Alder adducts with complete diastereocontrol. In each case an electron-rich double bond in the adduct is prone to a second addition of the heterocumulene. In the case of the oxazoline adducts the second addition is faster than the first, while with thiazolines the second addition is slower so that a different heterocumulene can be incorporated.

Improved conditions are reported for the Prins-pinacol rearrangement of cyclohexa-1,4-diene-derived acetals. The use of triflic acid gives particularly clean reaction, resulting in a mixture of regioisomers in an approximately 10:1 ratio. A tethered version of this reaction is also reported, giving a tricyclic compound with the same stereochemistry as the core of the cladiellin diterpenes.

Alkenyldihydrooxazoles undergo a highly diastereoselective formal aza-Diels–Alder reaction with aryl and arenesulfonyl isocyanates to give oxazolo[3,2-c]pyrimidines. Depending on the substitution pattern of the alkenyldihydrooxazole, these compounds may then undergo addition of a second equivalent of the isocyanate to give either tetrahydrooxazolo[3,2-c]pyrimidine-8-carboxamides or octahydroazeto[2,3-d]oxazolo[3,2-c]pyrimidines. The second addition is sensitive to steric and electronic factors, and can be prevented in some cases.

Diastereomerically pure oxazolo[3,2-c]pyrimidines can be readily prepared by the reaction of alkenyloxazolines with isocyanates. These compounds undergo epimerisation upon prolonged heating. The mechanism of this transformation has been investigated experimentally and computationally. Diastereomerically pure oxazolo[3,2-c]pyrimidines can be prepared by hetero-Diels-Alder reaction of alkenyloxazolines. The mechanism of the formation and isomerisation of these compounds is discussed.

Covering: 1 April 1998 to 30 June 1999. Previous review: J. Chem. Soc., Perkin Trans. 1, 1998, 4175.

Three novel dihydropyrimidine compounds N8,6-di(4-nitrophenyl)-(3R)-ethyl-(7R)-methyl-5-oxo-2,3,6,7-tetrahydrooxazolo[3,2,c] pyrimidine-8-carboxamide (2), N8,6-di((4-methylphenyl)-sulfonyl)-(3R)-ethyl-5-oxo-(7R)-phenyl-2,3,6,7-tetrahydrooxazolo [3,2,c]pyrimidine-8-carboxamide (3) and N8,6-di ((4-methylphenyl)sulfonyl)-(3R)-ethyl-(7R)-methyl-5-oxo-2,3,6,7-tetrahydrooxazolo[3,2,c] pyrimidine-8-carboxamide (4) have been prepared (from 2-amino-1-butanol of 64.4% e.e.) and structurally characterized by X-ray crystallography. All three compounds contain stereogenic centers, but the crystal of (2) chosen was found to be racemic whilst those of (3) and (4) were found to be homochiral. Compound (2) crystallizes in the monoclinic space group P21/c, with a = 17.958(4), b = 12.431(2), c = 9.653(2) A, beta = 96.20(3)°, U = 2142.3(7) A3, Z = 4, and D c = 1.449 g cm–3. Compounds (3) and (4) both crystallize in the monoclinic space group P21, with a = 9.349(2), b = 5.824(5), c = 26.513(8) A, beta = 99.43(2)°, U = 1424.1(13) A3, Z = 2 and D c = 1.389 g cm–3 for (3), and a = 5.9526(9), b = 16.3521(10), c = 13.2263(11) A, beta = 92.81(12)°, U = 1285.9(2) A3, Z = 2 and D c = 1.378 g cm–3 for (4).

The partial-reduction of aromatic compounds provides an important link between aromatic compounds and alicyclic compounds. This chapter covers advances in the field since the publication of the first edition of Comprehensive Organic Synthesis in 1991. The authors describe various aspects of the mechanism and reaction conditions used in the Birch reduction. Detailed coverage of the Birch reduction is organized by the type of aromatic compound being reduced, with many approaches being exemplified using target synthesis. Although the Birch reduction is still the most common method for the partial reduction of aromatic compounds, a number of variations on the Birch reduction are becoming more widely used. These methods are also described, along with a number of other methods using photochemistry, electrochemistry, transition metals, and enzymes.

Model studies towards the synthesis of the cytotoxic marine natural product diazonamide A are described. Three model 3-phenylbenzo[b]furan derivatives 5, 8 and 10 were prepared using rhodium(II) catalysed decomposition of the diazophenylacetate 3, Claisen rearrangement of the ether 7, and a classical intramolecular Friedel–Crafts reaction as key steps. Only the aromatic benzofuran system proved satisfactory in palladium coupling reactions; diazoacetyl(benzofuranyl)indole 18 was prepared by Suzuki coupling of (benzofuran-7-yl)boronic acid 11 with 4-bromoindole 14 to give 17, followed by diazo-transfer. Rhodium(II) catalysed decomposition of 18 in acetonitrile resulted in the formation of the 3,4-bridged indole 19 rather than the desired oxazole 20.

Derivatives of cyclohexa-1,4-diene diol 5 undergo highly diastereoselective free-radical cyclisation reactions. Selective reaction of either double bond is possible depending on the protecting groups used.

The crystal structure of the title compound, C26H39BO2, which contains no strong hydrogen bond donors, displays only long C—H...O contacts between inversion-related pairs of molecules. The structure contains layers rich in oxygen and boron parallel to the ac plane. The dioxaborinane ring adopts an envelope conformation with the C atom attached to the two methyl groups as the flap .

The reactions of bromomethyllithium with tert-alkylboronic esters could be of great potential for the formation of quaternary carbon centers, but often give poor yields/conversions. Calculations and experimental evidence show that tert-alkyl groups migrate less effectively than other types of alkyl group in such reactions, and that O migration competes. Furthermore, slow/incomplete capture of the bromomethyl reagent by the boronic ester is a problem in more hindered systems, and an additional competing reaction, possibly Li-Br exchange on the bromomethylborate species, also leads to lower yields of migrated products. Based on this, experimental protocols have been devised in which the competing reactions are largely suppressed, leading to higher conversions to migrated product for several substrates.

One of the key tasks in MIDTAL (MIcroarrays for the Detection of Toxic ALgae) is to demonstrate the applicability of microarrays to monitor harmful algae across a broad range of ecological niches and toxic species responsible for harmful algal events. Water samples are collected from a series of sites used in national phytoplankton and biotoxin monitoring across Europe. The samples are filtered; rRNA is extracted, labelled with a fluorescent dye and applied to a microarray chip. The signal intensity from >120 probes previously spotted on the chip is measured and analysed. Preliminary results comparing microarray signal intensities with actual field counts are presented.

An offshore operator in Malaysia had run a completion string in a highly deviated 7-in. gas well. When continuous pressure build-up in the production casing annulus was observed during well clean-up, leakage in the completion system was suspected. After several attempts to mitigate the pressure build-up failed, the operator initiated further investigation, which confirmed the suspicion. Small tubing leaks that were allowing produced gas inside the tubing to seep through to the annulus were found. These leaks could have allowed the pressure to increase, and possibly, could have caused the casing to collapse. In order to produce through the annulus, the pressure would have to be vented. With the high demand of gas in Malaysia and since the rig was still at the location, the project team decided to initiate immediate recompletion of the project instead of waiting for a later intervention. This well is one of three wells completed to develop the FN field within KCL area, located approximately 200 km offshore from Bintulu. The field was expected to deliver up to 100mmscf/day per well to help relieve an anticipated gas shortage. This paper discusses the history of the wells, the diagnostic methods used to analyze the well problems, the pros and cons of each solution considered, details regarding the recompletion chosen, and the challenges encountered during the recompletion activities. The discussion also highlights the successful solution used for closing and reopening the fluid loss isolation barrier valve (FLIBV) with a wireline tractor rather than with other options considered after conducting a successful system integration test (SIT) prior to the project execution. The unique solution chosen was a first for Malaysia, and probably, for the world. The success of the recompletion results provided improvements for future applications and will be a benchmark solution for future operations.

Abstract The demand for high capacity production in deep wells has increased interest inthe monobore concept, and thus, when an anticipated gas shortage was expectedin East Malaysia, this concept was considered as a possible strategy for afield in Malaysia which consists of a 3-well development. The targeted area, located approximately 200 km offshore from Bintulu, is expected to deliver100mmscf/day of gas to the Malaysian Liquified Natural Gas (MLNG) plants atBintulu, East Malaysia. New technology such as a tubing hanger profile, fluid-loss device, and glassreinforced epoxy (GRE) completion for large-bore wells and their firstapplication in this country will be presented along with the well requirements, work-over operations, and the innovative solution design developed. Details regarding the completion design, prior development, pre-job planning, asystem-integration test (SIT), operational challenges, and post-job discussionsconcerning the successful completion of these wells will be discussed, as thistype of completion was a first for Malaysia. The findings from the extensive development of the best solution for operationsand the challenges of the project cost objectives will be used to providelessons and improvements for future applications. Introduction The field developments consist of 10 new fields that will be developed in twophases. The first phase consists of 3 of the fields. The second phase consistsof 7 wells in each field, and these will be completed two to three years afterthe first field campaign. The second phase completion design will be based onthe design review and the lessons learned from the initial development. In each field, the first phase will be developed using 3 separate techniquesthat have been identified for each field. The wells have been chosen to bedeveloped as single monobore completions, whereas the other two fields will bedeveloped as openhole sand-control completions and subsea completions. Eachtechnique was chosen to be part of the Petronas long-term vision to train thelocal project team with new technologies and prepare them with basic guidelinesfor the second phase field development. Although all of these completiontechniques have been installed in other regions by other major oil operators, they were new concepts for the project team, and therefore, would provide newcompletion experience.

Obscurin (also known as Unc-89 in Drosophila) is a large modular protein in the M-line of Drosophila muscles. Drosophila obscurin is similar to the nematode protein UNC-89. Four isoforms are found in the muscles of adult flies: two in the indirect flight muscle (IFM) and two in other muscles. A fifth isoform is found in the larva. The larger IFM isoform has all the domains that were predicted from the gene sequence. Obscurin is in the M-line throughout development of the embryo, larva and pupa. Using P-element mutant flies and RNAi knockdown flies, we have investigated the effect of decreased obscurin expression on the structure of the sarcomere. Embryos, larvae and pupae developed normally. In the pupa, however, the IFM was affected. Although the Z-disc was normal, the H-zone was misaligned. Adults were unable to fly and the structure of the IFM was irregular: M-lines were missing and H-zones misplaced or absent. Isolated thick filaments were asymmetrical, with bare zones that were shifted away from the middle of the filaments. In the sarcomere, the length and polarity of thin filaments depends on the symmetry of adjacent thick filaments; shifted bare zones resulted in abnormally long or short thin filaments. We conclude that obscurin in the IFM is necessary for the development of a symmetrical sarcomere in Drosophila IFM.