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Foamed cement was successfully used in the riserless section of an ultradeepwater well located in 11,900ft water depth. Foamed cement was selected to minimize operating costs and provide flexibility to adjust slurry density on a short notice. The seawater column exerted 5,319.1-psi hydrostatic pressure on the annulus. Consequently, nitrogen (N2) density could no longer be neglected. This paper presents simulations performed in preparation for the job, operational considerations, and post-job evaluation. The lead slurry needed a density of 1.25 SG and develops a compressive strength of at least 300 psi within 48 hr. Considering the cost and challenges associated with outsourcing resources under current Covid-19 pandemic restrictions, the foamed cement system was preferred over chemical- or particle- extended cement or blend systems. The N2 ratio for the foamed cement slurry system was 700 scf/bbl. With a base slurry pumping rate of 5 bbl/min, the required N2 pumping rate was 3,500 scf/min, which was greater than the capability of a single N2 pump (3,000-scf/min rate). Because the rig deck space could not accommodate three N2 pumps, one pump would serve as backup; thus, the final plan consisted of using two N2 pumps simultaneously. Two parallel foamed slurry treating lines were rigged up to reduce the fluid velocity in a single line. All laboratory testing was conducted locally. Additives used in the foamed slurry were environmentally friendly. A proprietary process-control system was used during the cementing operation and automatically synchronized the N2 pumps and foam pump rates with the base slurry rate. The cementing crew consisted of 11 individuals, including 2 client representatives. The entire pumping operation was completed in 10 hr. A total base slurry volume of 1016.2 bbl was continuously mixed and pumped at the density of 13.35 lbm/gal (1.60 SG). The resulting foamed slurry volume was 1387.0 bbl with an average foam quality of 27.8% and foamed slurry density of 10.5 lbm/gal (1.26 SG). A total of 119 metric tonne of class G cement and 30,711 L of N2 were consumed during the pumping operation. The lead slurry was followed by 603.9 bbl of 15.86 lbm/gal (1.90 SG) class G cement tail slurry and 349.7 bbl of seawater for displacement. The final surface pressure was 594.6 psi. The lead slurry reached the seabed and the float shoe check was positive. No casing subsidence was observed. Using foamed cement slurry in such extreme conditions demonstrated its robustness and reliability. Through formalized and methodical risk assessment, the team was able to identify and implement mitigating measures that led to an outstanding result. This application also confirmed that N2 density should not be neglected when high-hydrostatic pressure is involved.

The Tuz Gölü underground gas storage (UGS) project is a strategic venture in Turkey's energy program. This gas storage facility will be the largest in Europe, having multibillion m3 capacity, by taking advantage of the optimal gas storage conditions offered by subterranean salt caverns. Upon reaching the reservoir, one of the important goals is to obtain hydraulic isolation between the surface and the casing. Inadequate downhole isolation may well result in interzonal communication, gas migration, casing corrosion, and sustained casing pressure. Furthermore, gas flow to surface formations and/or to the atmosphere, could impact the environment and health along with an underlying economic impact. Wellbore isolation was introduced in the form of fully salt-saturated gas control and self-healing cement systems. When drilling into salt caverns, the foremost challenge is to minimize the dissolution of the in-situ salt formation by means of contact with water-based cementing fluids, which can lead to the creation of new flow paths. This occurrence must be prevented at all costs; otherwise, stored gas might leak through these microchannels. Unlike typical salt formations, this candidate field also contains carbon dioxide (CO2). Most wells in the field had a prognosis toward low CO2 content, so cement exposure to CO2 was not deemed an elevated risk; however, if the CO2 exposure risk increased, it would potentially generate an additional challenge both in terms of gas migration control and long-term cement integrity. Currently, more than 100 cementing operations have been performed in the candidate field. After pumping 3,500 metric ton of cement and blending 750 metric ton of the tailored self-healing cement, more than 300 laboratory tests were performed. More than 15,000 staff-hours of testing supported construction of 32 UGS wells, fully cemented with zero health, safety, and environment (HSE) or service quality incidents and, importantly, with outstanding bond log results. Completion strings in 15 wells have already been run where wells are prepared to store gas; the ongoing project is now expanded to 50 UGS wells. Furthermore, an intrinsic benefit of the self-healing cement system is reduced CO2 footprint vs. conventional class G cement, which can be nominally 40% less CO2 per unit volume. With involvement of local laboratories and technical experts in the region, salt-saturated gas-control and self-healing cement slurry systems have been developed and successfully deployed. Information regarding these system's liquid and set properties will be presented, along with techniques used to enhance certain cement properties. The field cases that will be presented describe how challenges were overcome in successfully sealing UGS wells in a highly saline environment, and how the self-healing technology applied in these wells is being extended to include salt-saturated systems and CO2-resistant versions elsewhere.

A 1575m [4922-ft] offshore horizontal 4-½-in. liner cemented using a mud-sealing cement system (MSCS) resulted in an outstanding cement bond log result. The decision to use the MSCS was taken after realizing that four offset liners, previously cemented using conventional cement systems, did not yield acceptable cement bond log results despite following oil and gas cementing industry best practices, including pipe rotation. This paper documents a comparison of six offset horizontal liners, focusing on the impact of the MSCS technology. The paper focuses on several 4-½-in. liners in the same field. The wells were drilled by a similar rig and had similar well profiles. The drilling bit, directional drilling tool, drilling fluids system, logging tool, centralizer type and pumping sequences were comparable across all wells. In addition, the logging company performing the cement bond log evaluation was not the same company performing the cementing service. After the first MSCS-cemented well, the subsequent well used a conventional cement system to isolate the 4-½-in. liner and tighten the cementing best practices. This was initiated to irrefutably confirm the impact of MSCS technology on the quality of cement bond log recorded on the earlier well. The cement bond log recorded from the well isolated with MSCS is easily identified among the six comparison wells even though the cementing operation faced several well challenges, includinga single dart liner system implementation (for all liners), which can promote the intermixing of slurry with fluid ahead while travelling down the pipemud losses in the drilling phase, which resulted in a reduction of the displacement rate to control ECD during cement placement. The bond log results of the other wells were qualified as poor or fair, even though significant precautions were taken to optimize zonal isolation. These efforts included batch mixing the spacer and slurry, using more than one centralizer per casing joint, and implementing pipe rotation during pre-job circulation and job execution when the torque limit allowed. This multi-well comparison based on field results brings solid evidence of the MSCS technology interacting with the residual layer of nonaqueous fluid (NAF) when well conditions reach or exceed the practical normative limitations for mud removal. This in-situ interaction generates a viscous paste that positively impacts the bond log response and bolsters the isolation between zones of interest. The result has yielded a step forward in the provision of a dedicated barrier technology for horizontal or highly deviated sections.

Summary Globally, there is an increasing focus on hydrocarbon recovery in regions that are new to environmental legislation and regulation; very often, these are offshore environments where well integrity has broad effects. Providing environmentally compliant fluids is becoming a standard, and thus expertise in regulations and “green” chemistry is rapidly being pulled from established regions such as the North Sea. The expectation that both regulations and necessary chemistry can be slotted into the new region's operations is difficult to achieve because there is no single set or universal set of regulations; therefore, there is no “one-size-fits-all” solution. This paper addresses numerous distinct challenges for cementing-related fluids and how the changing regulatory stage across different regions can be optimally managed. Indeed, because these regions can be “frontier” or remote in nature, emphasis on cost control from operators is high to minimize the well-construction cost. This may not align with environmental compliance expectations. Particular examples from West Africa will be presented to highlight challenges toward conformity with the aim of discussing the pitfalls and potential solutions available. Environmental regulations and practices are continually evolving, and they come under increasing scrutiny at the well-planning stage, with heavy emphasis on well integrity and cementing quality. The most-legislated region of offshore exploration and production is the North Sea, and, naturally, governing bodies and operators are adopting North Sea regulatory models elsewhere. Through case histories covering North Sea, French Guiana, and West Africa, a systematic review of the numerous approaches governing the application of cementing fluids for well integrity will be deliberated. An innovative “green” chemistry solution for high-pressure/high-temperature (HP/HT) operations, developed to tackle compliance with Norwegian North Sea regulations, will act as key example of steps taken to safeguard global environmentally sensitive regions and ensure long-term well integrity.

In recent years, a project was initiated to identify a safe and practical alternative to conventional silica-based cement slurries. The objective was to eliminate exposure to respirable crystalline silica (RCS) in oilfield cementing operations. RCS, as well as being linked to various respiratory illnesses (1), has now been identified as a human lung carcinogen (2), implying there is an established link between exposure to RCS and lung cancer. When cementing well sections with a bottomhole static temperature (BHST) of over 110°C [230°F], a cement powder containing silica flour must be used to ensure the set cement matrix is stabilized to be able to withstand persistent exposure to these temperatures over time (mitigating against strength retrogression). A certain proportion of the silica within these conventional cement blends is classified as RCS. The newly developed system, known as zero respirable crystalline silica blend or ‘ZRCS-blend’, was successfully applied on numerous occasions on a Norwegian rig. Interestingly, the system found successful application in a batch-drilled conductor campaign on a high-pressure/high-temperature (HPHT) field where the potential exposure during production exceeded 110°C [230°F]. Whilst being a safer alternative to conventional cement systems, the ZRCS-blend was able to deliver a top of cement (TOC) to the seabed on each and every occasion during the campaign, thus eliminating the need for any remedial operations. As shown by proven success of the ZRCS-blend offshore on the Norwegian continental shelf, the system provides an alternative to silica-based cement for operations worldwide, to comply with regulations and health, safety, and environmental guidelines.

Globally, there is increasing focus on hydrocarbon recovery in regions that are new to environmental legislation and regulation; very often this is an offshore environment where well integrity has broad effects. Providing environmentally compliant fluids is standard, and thus expertise in regulations and “green” chemistry is rapidly being pulled from established regions such as the North Sea. The expectation that both regulations and the chemistry can be slotted into the new region's operations is difficult to achieve, as there is no single set or universal set of regulations; so no ‘one-size-fits-all’ solution. This paper addresses numerous distinct challenges for cementing-related fluids and how the changing regulatory stage across different regions can be optimally managed. Indeed, as these regions can be “frontier” or remote in nature, emphasis on cost control from operators is high to minimize the well construction cost. This may not align with environmental compliance expectations. Particular examples, from West Africa, will be presented to highlight challenges toward conformity with the aim of discussing the pitfalls and potential solutions available. Environmental regulations and practices are continually evolving, and come under increasing scrutiny at the well planning stage, with heavy emphasis on well integrity and cementing quality. The most legislated region of offshore E&P is the North Sea, and, naturally, governing bodies and operators are adopting North Sea regulatory models elsewhere. Through case histories covering North Sea, French Guiana, West Africa, the Arctic, Canada, and Australia, a systematic review of the numerous approaches governing the application of cementing fluids for well integrity will be deliberated. An innovative “green” chemistry solution for high-pressure/high-temperature (HP/HT) operations, developed to tackle compliance with Norwegian North Sea regulations, will act as key example of steps taken to safeguard global environmentally sensitive regions and ensure long-term well integrity.

The enzymatic desymmetrization/resolution of epoxydiols generated from the basic epoxidation and reduction of 1,4-naphthoquoinone, 5-hydroxy-1,4-naphthoquinone and 5,8-dihydroxy-1,4-naphthoquinone is described. 2,3-Epoxy-1α,2α,3α,4α-tetrahydronaphthalene-1,4-diol and 5,8-diallyloxy-2,3-epoxy-1α,2α,3α,4α-tetrahydronaphthalene-1,4-diol were desymmetrized in the presence of isopropenyl acetate using Burholderia cepacia lipase and Candida antartica lipase B, respectively. An enzymatic resolution of 8-benzyloxy-2,3-epoxy-1α,2α,3α,4α-tetrahydronaphthalene-1,4-diol using B. cepacia lipase in isopropenyl acetate is also described.

Mutagenesis of the human A(3) adenosine receptor (AR) suggested that certain amino acid residues contributed differently to ligand binding and activation processes. Here we demonstrated that various adenosine modifications, including adenine substitution and ribose ring constraints, also contributed differentially to these processes. The ligand effects on cyclic AMP production in intact CHO cells expressing the A(3)AR and in receptor binding were compared. Notably, the simple 2-fluoro group alone or 2-chloro in combination with N(6)-substitution dramatically diminished the efficacy of adenosine derivatives, even converting agonist into antagonist. Other affinity-increasing substitutions, including N(6)-(3-iodobenzyl) 4 and the (Northern)-methanocarba 15, also reduced efficacy, except in combination with a flexible 5′-uronamide. 2-Cl-N(6)-(3-iodobenzyl) derivatives, both in the (N)-methanocarba (i.e., of the Northern conformation) and riboside series 18 and 5, respectively, were potent antagonists with little residual agonism. Ring-constrained 2′,3′-epoxide derivatives in both riboside and (N)-methanocarba series 13 and 21, respectively, and a cyclized (spiral) 4′,5′-uronamide derivative 14 were synthesized and found to be human A(3)AR antagonists. 14 bound potently at both human (26 nM) and rat (49 nM) A(3)ARs. A rhodopsin-based A(3)AR model, containing all domains except the C-terminal region, indicated separate structural requirements for receptor binding and activation for these adenosine analogues. Ligand docking, taking into account binding of selected derivatives at mutant A(3)ARs, featured interactions of TM3 (His95) with the adenine moiety and TMs 6 and 7 with the ribose 5′-region. The 5′-OH group of antagonist N(6)-(3-iodobenzyl)-2-chloroadenosine 5 formed a H-bond with N274 but not with S271. The 5′-substituent of nucleoside antagonists moved toward TM7 and away from TM6. The conserved Trp243 (6.48) side chain, involved in recognition of the classical (nonnucleoside) A(3)AR antagonists but not adenosine-derived ligands, displayed a characteristic movement exclusively upon docking of agonists. Thus, A(3)AR activation appeared to require flexibility at the 5′- and 3′-positions, which was diminished in (N)-methanocarba, spiro, and epoxide analogues, and was characteristic of ribose interactions at TM6 and TM7.

Syntheses of protected derivatives of both enantiomers of trans-4-hydroxypipecolic acid (2) and the natural product (−)-SS20846A (3) were accomplished from vinylglycinols. Key transformations involved construction of the piperidine ring via ring-closing metathesis (Grubbs’ catalyst) and installation of the 4-hydroxy substituent by Prevost reaction. X-Ray diffraction analyses conclusively established the regio- and stereochemistry of key intermediates.

[formula: see text] (R and S)-alpha-Amino alcohols and alpha-amino acids, including 4-methoxyhomophenylalanine, with a variety of unnatural side chains have been synthesized via palladium-catalyzed cross-coupling Suzuki reactions. The key building blocks 1 and 2, synthesized from the common achiral precursor 2-butene-1,4-diol, were made enantiopure utilizing a Pseudomonas cepacia lipase-catalyzed kinetic resolution. The optimal conditions for the Suzuki cross-coupling and the subsequent oxidations of the resultant alpha-amino alcohols are described.

Is the discharge from a combined sewer overflow (CSO) control facility clean enough to meet water quality standards? What in-stream impacts should be measured? How can the in-stream impacts of CSO be evaluated when there are other sources of wet weather pollution in the watershed? When is there enough data to make decisions? These are the questions being answered by the Rouge River National Wet Weather Demonstration Project in metropolitan Detroit. Nine new facilities for storing and treating CSO discharges have been constructed and placed into operation along the Rouge River since 1997. A detailed evaluation is underway to examine the performance of the facilities and the water quality impacts of their discharges. This paper focuses on the in-stream evaluation of four criteria: • The water quality standard for dissolved oxygen • The physical characteristics standard • The total residual chlorine standard • The health of the biological community (as a surrogate for toxic materials) The evaluation is being performed in the context of a number of watershed restoration efforts on the Rouge River. These other efforts include: illicit discharge elimination, storm water management, abandoned dump remediation, and habitat and recreational improvements. In the Rouge Watershed, CSO discharges are being controlled in three phases: • Phase 1 – public health protection for approximately 30 percent of the combined sewer area • Phase 2 – public health protection for the remaining combined sewer area • Phase 3 – meet water quality standards in the river (not necessarily in the whole effluent) for all combined sewer overflows The nine facilities being evaluated are part of Phase 1. The evaluation of the Phase 1 facilities will lead to the basis of design for Phase 2 and Phase 3. The answers will determine the level of additional investment required for completion of CSO control in Phase 2 and Phase 3.

The conformational behavior of different aza-C-glycosides synthesized as glycosidase inhibitors has been studied using a combination of NMR spectroscopy (J and NOE data) and time-averaged restrained molecular dynamics calculations. The obtained results show that the population distribution of conformers around their pseudoglycosidic linkages is mainly controlled by 1,3-syn-diaxial interactions. Electrostatic effects slightly modulate the conformational equilibrium. This result is in contrast with that observed for O-glycosides. For these natural compounds, the conformational behavior around the glycosidic linkage Φ is mainly governed by the exo-anomeric effect. Experimentally based energy values for both the 1,3-syn-diaxial interactions and the stereoelectronic effect have been deduced. Finally, the inhibitory activity of these compounds has been tested again a variety of glycosidase enzymes.

A strategy based on the use of (trifluoromethyl) trimethylsilane for introduction of the trifluoromethyl group at the C-4 of ribose has been developed and utilized in the synthesis of various novel 4′-trifluoromethylated nucleoside analogs. Screening of these analogs against HIV did not reveal significant biological activity.

A newly synthesized cyclic hydroxamic acid compound, BMD188 [cis-l-hydroxy-4-(l-naphthyl)-6-oc-tylpiperidine-2-one], was found to induce the apoptotic death of cultured prostate cancer cells by activating caspase-3. Orally administered BMD188 significantly inhibited the primary growth of prostate cancer cells (Dul45) orthotopically implanted into SCID mice. Mechanistic studies indicated that BMD188 did not alter the protein levels of several Bcl-2 family members. In contrast, the BMD188 effect required three essential factors: reactive oxygen species (ROS), the mitochondrial respiratory chain function, and proteases. First, the apoptosis-inducing effect of BMD188 could be blocked by ROS scavengers such as Desferal. Second, both BMD188-induced PARP cleavage as well as PC3 cell apoptosis could be dramatically inhibited by several complex-specific mitochondrial respiration blockers. The involvement of mitochondria was also supported by the observations that BMD188 dramatically altered the mitochondrial distribution and morphology without affecting the cellular ATP levels. Finally, the apoptosis-inducing effect of BMD188 in PC3 cells could be significantly inhibited by serine protease inhibitors (TPCK and TLCK) as well as by caspase inhibitors (zVAD-fmk and DEVD-CHO). Collectively, the present study suggests that BMD188 and its analogs may find clinical applications in the treatment of prostate cancer patients by inducing apoptotic death of prostate cancer cells.

Diol 2, derived in two steps from p-benzoquinone, was converted to epoxy alcohol 3. The latter was resolved with crude Candida rugosa lipase in isopropenyl acetate/toluene to give acetate (−)-4 and residual alcohol (+)-3. Oxirane ring opening reactions of 3 and the corresponding acetate and TBDMS derivatives with a variety of nucleophiles gave diastereomerically pure 3,4,5,6-tetrasubstituted cyclohexene derivatives of type 6. X-ray crystal structures were obtained on compounds 6e, 6m and the diacetate prepared from 6l. Nitrogen nucleophiles provided entry in various aziridines 10. Pd(0)-catalyzed nucleophilic additions to substrate 5 cleanly provided the diastereomeric pattern of type 11. trans-5,6-Disubstituted cyclohexadienes 13 were obtained by an unusual syn-reductive elimination on bromocarbonates 12 utilizing Pd or Zn.

A synthesis of the non-opiate analgesic alkaloid epibatidine was achieved in 13 steps and 13% overall yield starting from 1,3-cyclohexadiene using in a key step a modified Stille coupling reaction on an α-iodocyclohexenone.

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were found to be nonsteroidal antiinflammatory and analgesic agents. These compounds are inhibitors of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX) with selectivity for the COX-2 isoform. A series of analogues were prepared to investigate the scope of this lead. Five ketone side chains from active DHDMBFs were used to investigate the effects of changes in the DHDMBF "core": the size and identity of the heterocycle and the substituent requirements of the heterocycle and phenyl ring. Biological testing showed that a variety of structural changes can be accommodated, but no structure was clearly superior to the DHDMBF structure.

Biocatalytically generated enantiopure intermediates are exceptionally valuable as starting materials in the syntheses of enantiopure complex organic compounds. Cyclic intermediates are particularly useful because of their inherent tendency to undergo highly diastereoselective transformations. Techniques such as the asymmetrization of meso compounds making either enantiomer available in superior yields, and the employment of enzymes at low temperatures giving improved enantioselectivities promise to facilitate the preparation of such intermediates. Because of their functional group compatibility, their environmentally safe nature, and often their low cost, biocatalysis have become a well recognized means of introducing enantiopurity in organic synthesis.

Double Suzuki coupling was achieved with vinyl bromide 7 , synthesized from the bromobenzene microbial oxidation metabolite bromocyclohexadienediol 6 and α,ω-diborane coupling partners derived from the hydroboration of the corresponding diene. Ozonolysis and selective reduction protocols served to provide selectively theα/α or β/β tethered polyhydroxylated piperidine ring systems (bis-azabugars). The C 8 linked DMJ analogue 1 showed inhibitory activity against glycosidase enzymes.

Methodology for the construction of diverse α-1- C -substituted-deoxymannojirimycin analogues is reported. The pseudoanomeric carbon-carbon bond was formed using a Suzuki cross-coupling between vinyl bromide 5 , derived biocatalytically from bromobenzene, and an aryl, alkyl, or carbohydrate boron coupling partner. Ozonolysis and stereoselective reduction followed by an intramolecular nucleophilic ring closing served to form the polyhydroxylated piperidine ring. © 1997 Elsevier Science Ltd.

The synthesis of 11 β-1-C-aryl-deoxymannojirimycin analogues using a versatile de novo strategy is described. The origins of this report are derived from several recent developments in the area of C1-substituted glycomimetic polyhydroxylated piperidines. This study is designed as a structure−activity comparison to explore the effects of aryl substitution on the ability of the title compounds to inhibit glycosidase enzymes. The polyhydroxylated piperidine ring was constructed using vinyl bromide 10, which was synthesized in six steps from the bromobenzene microbial oxidation metabolite bromo diol 9. A palladium-catalyzed Suzuki cross-coupling of vinyl bromide 10 and the corresponding arylboronic acid served as the key pseudoanomeric carbon−carbon bond-forming step. Ozonolysis and selective reduction of the resultant carbonyl functions followed by reductive amination served to produce the azasugar ring. The complete NMR analysis of the resultant piperidine ring stereochemistry is also discussed. Fully depro...

The synthesis of (1→6), (1→4), and (1→1) linked aza-C-disaccharides, a novel class of glycomimetic compounds, is described. The polyhydroxylated piperidine ring was synthesized using vinyl bromide 11 as a common intermediate which was synthesized de novo from bromobenzene utilizing the microbial oxidation metabolite bromodiol 10. A Suzuki coupling of 11 with an alkylboron reagent derived from olefinated carbohydrate precursors via hydroboration was used to form the C-glycosidic bond. Ozonolysis and selective reduction of the resultant carbonyl functions served to produce the azasugar ring. Fully deprotected aza-C-disaccharides were obtained upon acidic deprotection. Biological screening of the title compounds against several common glycosidase enzymes as well as in vitro anti-HIV assays are reported.

(1 R ,4 S ,6 S )-4-Acetoxy-6-triisopropylsilyloxy-2-cyclohepten-1-ol, prepared from cycloheptatriene utilizing an asymmetrization of the precursor diol with Candida antarctica lipase B/isopropenyl acetate, was converted to (1 S ,3 R ,4 S ,5 S ,6 R ,7 R )-4,6,7-triacetoxy-5-benzyloxymethyl-4-acetoxymethyl-2,8-dioxabicyclo[3.2.1]octane representing the core of zaragozic acid by a strategy involving Rubottom oxidations and ozonolysis.

The title cyclopentenone has been prepared by enzymatic resolution of cis -4-phenyloxy- and cis -4-(4-methoxyphenyloxy)-cyclopent-2-en-1-ol in isopropenyl acetate using Pseudomonas cepacia lipase. The use of a 4-methoxyphenyloxy-alcohol intermediate enabled the use of both enzymatically resolved enantiomers in the synthesis of the desired (+)-enone.

A series of (carboxyalkyl)benzyl propargyl ethers was synthesized and tested as inhibitors of 12-lipoxygenase (12-LO) from porcine leukocyte cytosol. Optimum activity was displayed by 3-[4-[(2-tridecynyloxy)methyl]phenyl]propanoic acid. Altering the length of the alkyl side chain attached to the acetylenic group reduced activity. Changing the substitution pattern in the (carboxyalkyl)benzyl group from para to meta or ortho also reduced activity. Analogs in which the triple bond was replaced by a double bond or an allene displayed reduced activity, whereas fully saturated analogs were inactive. High concentrations (10 microM) of the most potent acetylenic (carboxylalkyl)benzyl ethers did not inhibit human platelet 12-LO, human neutrophil 5-LO, rabbit reticulocyte 15-LO, or soybean 15-LO. Thus, this class of compounds represents the first example of isoform specific LO inhibitors.

The taxol intermediate, racemic 3, was subjected to two consecutive kinetic resolutions with recombinant Candida antarctica lipase B in isopropenyl acetate/hexane. The absolute stereochemistry of the resulting acetate (+)-5 of > 99% enantiopurity, was assigned based on NMR and CD methods.

(3-C-trifluoromethyl-β-D-ribofuranosyl) nucleosides of thymine, uracil and adenine were synthesized from 5-O-benzoyl-1, 2, 3-tri-O-acetyl-3-C-trifluoromethyl-β-D-ribofuranoside, prepared by addition of CF3SiMe3 to 5-O-benzoyl-1, 2-O-isopropylidene-α-D-erythro-pentos-3-ulose. 9-(3-C-Trifluoromethyl-β-D-ribofuranosyl)adenine was active against HSV-1.

Enantiopure enones obtained via lipase asymmetrization of meso -diols derived from cycloheptatriene underwent tin-directed ring-openings to give syn -1,3-bis(silyloxy) olefins which were converted to their acetonides in a one-pot sequence.

Synthesis of a novel aza- C -disaccharide is described using a Suzuki coupling of the alkyl boron reagent 8 and vinyl bromide 7 as the key step.

meso -Diol 4 , derived from 1,5-cyclooctadiene, in the presence of Pseudomonas cepacia lipase in isopropenyl acetate, afforded enantiopure 5 , an attractive intermediate for the synthesis of sugars and related compounds.

Both meso diastereomers of 6-[tert-butyldimethylsilyl)oxy]-2-cycloheptene-1,4-diol, prepared from cycloheptatriene, have been enzymatically asymmetrized by conversion to monoacetates using Pseudomonas cepacia lipase in isopropenyl acetate. A study of protecting group manipulations, diastereoselective oxidations, and regioselective ring openings utilizing these enantiopure monacetates which results in the synthesis of all possible methyl 2,4-dideoxyhexopyranosides is described

The meso -diol and corresponding diacetates of cycloheptene derivatives were subjected to enzymatic asymmetrizations utilizing Pseudomonas cepacia lipase in organic and aqueous media. These biotransformations illustrate the enantio-complementary nature of enzymatic reactions in organic and aqueous media.

An efficient enzymatic resolution of racemic 4-acetoxy-2,3-dibromo-5-cyclohexen-1-ol in organic solvent is described. The methodology is extended to the synthesis of a series of highly functionalized enantiopure intermediates derived from various substituted p-benzoquinones.

The title compounds have been prepared by a route involving the elaboration of meso-cyclohexa-3,5-diene-1,2-diol 4, a product of microbial oxidation of benzene, to meso-diol 6 and asymmetrization of the latter by use of a lipase in organic media to the enantiometrically pure monoacetate 7.

The preparation of all possible methyl 2,4-dideoxyhexopyranosides starting from optically pure enzymatic asymmetrization products1 and 2 is reported.

α-Iodoenones undergo Pd-catalyzed coupling with alkenyl- and aryl-tributylstannanes providing an efficient route to the corresponding α-substituted enones.

Cyclopentadiene, benzene and cycloheptatriene were transformed to functionalized meso-diols. The resulting meso-diols or their corresponding meso-diacetates were subjected to enzymatic asymmetrizations using enzymes, particularly lipases, in organic or aqueous media. Examples of the use of the resulting aracemic products in the synthesis of a variety of polyols of biological interest are reviewed. We are engaged in a program of synthesis of bioactive molecules by routes involving the following features: Readily available cyclic starting materials are subjected to stereospecific oxidation reactions which serve to set relative ring stereochemistry and produce compounds of the stereochemical class meso. These meso compounds are asymmetrized by use of enzymes to set absolute stereochemistry about the ring. Further manipulation then provides useful new chiral pool intermediates which are carried on to target molecules. In many instances, regioselective ring cleavage reactions are used to unveil acyclic compounds with fixed absolute stereochemistry. In this overview of recent efforts from our laboratory we will provide a synopsis of chemoenzyhatic approaches to various bioactive targets utilizing the following as starting materials

meso-2-Cycloalken-1,4-diols or the corresponding diacetates with five-, six-, and seven-membered rings were subjected to enzymatic asymmetrizations utilizing a recombinant version of lipase B from Candida antarctica (Novo SP-435) in organic or aqueous media.