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OPTIMIZATION OF A MINATURE TRANSMITTER MODULE FOR WIRELESS TELEMETRY APPLICATIONSOsgood, Karina, Burke, Larry, Webb, Amy, Muir, John, Dearstine, Christina, Quaglietta, Anthony 10 1900 (has links)
International Telemetering Conference Proceedings / October 21, 2002 / Town & Country Hotel and Conference Center, San Diego, California / M/A-COM, Inc. has previously developed a highly integrated transmitter chip set for wireless telemetry
applications for the military L and S band frequencies and the commercial 2.4GHz ISM band. The original
chip set is comprised of a voltage controlled oscillator (VCO), a silicon phase locked loop (PLL), and a
family of power amplifiers (PA's). Using these components, M/A-COM has produced a miniature IRIG-compliant
transmitter module, which has been flight-tested by the U.S. Army’s Hardened Subminiature
Telemetry and Sensor System (HSTSS) program. Since the initial offering, several product enhancements
have been added. The module performance has been improved by tailoring the VCO specifically for direct
frequency modulation applications. In addition to improving noise performance, these enhancements have
produced improved modulation linearity, decreased lock time and increased carrier stability. Modulation
rates in excess of 10Mbps have been demonstrated. High efficiency power amplifiers operating at 3V have
also been added to the family of amplifiers (PAE > 50%). This greatly enhanced efficiency allows higher RF
power output while maintaining the same miniature form factor for the transmitter. Further, M/A-COM has
added a silicon-on-sapphire PLL to the chip set, which operates at frequencies up to 3.0GHz. This paper
details the enhancements to the components within the chip set, and the improvement in performance of the
transmitter module. Test data is presented for the transmitter modules and individual components.
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Misoprostol for prevention and treatment of postpartum hemorrhage : a systematic reviewOlefile, Kabelo Monicah 12 1900 (has links)
Thesis (MCur)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Background: Misoprostol, a prostaglandin E1 analogue with its uterotonic properties
has entered as an integral part of management of the third stage of labour, helping to
prevent postpartum haemorrhage (PPH).
Objective: To assess evidence on the effectiveness of misoprostol compared to a
placebo for the prevention and treatment of postpartum haemorrhage.
Methods: Databases searched included; MEDLINE, Google Scholar and Cochrane
Central Register of Controlled Trials (CENTRAL). Other sources were also searched.
All articles were screened for methodological quality by two reviewers independently by
standardized instrument. Data was entered in Review Manger 5.1 software for analysis.
Results: Three Misoprostol studies were included (2346 participants), Oral (2 trials) and
sublingual (1 trial). Misoprostol has shown not to be effective in reducing PPH (RR
0.65: 95% CI 0.40-1.06). Only one trial reported on need for blood transfusion (RR
0.14; 95% CI 0.02-1.15). Misoprostol use is associated with significant increases in
shivering (RR 2.75; 95% CI 2.26-3.34) and pyrexia (RR 5.34; 95% CI 2.86-9.96) than
with placebo. No maternal deaths were reported in included trials. Compared to
placebo, misoprostol was coupled with less hysterectomies and additional used of
uterotonics (RR 0.45; 95%CI 0.21-0.96) compared to placebo.
Conclusion: Results of this review shows that the use of misoprostol in combination
with some components of active management was not associated with any significant
reduction in incidence of PPH. However oral administration showed a significant
reduction in incidence of PPH. For its use for treatment of postpartum haemorrhage,
there is a need for research focus in optimal dose and route of administration for a
clinically significant effect and acceptable side effects. / AFRIKAANSE OPSOMMING: Agtergrond: Misoprostol, 'n prostaglandien E1 analoog met sy uterotonic eienskappe
het ingeskryf as' n integrale deel van die bestuur van die derde stadium van kraam, help
postpartum bloeding (PPH) te voorkom.
Doelwit: Om bewyse oor die effektiwiteit van Misoprostol in vergelyking met 'n placebo
vir die voorkoming en behandeling van postpartum bloeding te evalueer.
Metodes: Databases gesoek ingesluit, Medline, CINHAL, Google Scholar en Cochrane
Sentrale Register van gecontroleerde studies (Sentraal). Ander bronne is ook
deursoek. Alle artikels is gekeur vir die metodologiese kwaliteit deur twee beoordelaars
onafhanklik deur die gestandaardiseerde instrument. Data is opgeneem in Review
Manger 5.1 sagteware vir ontleding.
Hoof Resultate: Drie Misoprostol studies were ingesluit (2346 deelnemers). Mondeling
(2 proe) en sublinguale (1 verhoor). Misoprostol het getoon nie doeltreffend te wees in
die vermindering van PPH (RR 0,65: 95% CI 0,40-1,06). Slegs een verhoor berig oor
die noodsaaklikheid vir 'n bloedoortapping (RR 0,14, 95% CI 0,02-1,15). Misoprostol
gebruik word geassosieer met 'n aansienlike toename in bewing (RR 2,75, 95% CI 2,26-
3,34) en koors (RR 5,34, 95% CI 2,86-9,96) as met' n placebo. Geen moederlike
sterftes is aangemeld in proewe. In vergelyking met placebo, was Misoprostol tesame
met minder hysterectomies en addisionele gebruik van uterotonics (RR 0,45, 95%
CI,21-,96) in vergelyking met placebo.
Gevolgtrekking: Resultate van hierdie studie toon dat die gebruik van Misoprostol in
kombinasie met 'n paar komponente van aktiewe bestuur is wat nie verband hou met' n
beduidende afname in die voorkoms van PPH. Vir die gebruik vir die behandeling van
postpartum bloeding, daar is 'n behoefte vir navorsing fokus in die optimale dosis en die
roete van administrasie vir' n klinies beduidende uitwerking en aanvaarbare neweeffekte.
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Μελέτη, σχεδίαση και κατασκευή ταλαντωτών χαμηλού θορύβου φάσηςΦίλιππας, Σταύρος 13 October 2013 (has links)
Στη παρούσα διπλωματική εργασία μελετήθηκε, σχεδιάστηκε, προσομοιώθηκε και κατασκευάστηκε ένα σύστημα ενός ταλαντωτή το οποίο μειώνει τον θόρυβο φάσης (phase noise) σε εικονικά οποιονδήποτε ήδη υπάρχον ταλαντωτή ελεγχόμενου από τάση (VCO). Για να το πετύχει αυτό η προτεινόμενη τεχνική δανείζεται από την ιδέα του βρόχου κλειδωμένης φάσης (Phase Locked Loop) και με λίγα επιπλέον ηλεκτρονικά στοιχεία καθιστά δυνατή την μείωση του phase noise επηρεάζοντας σε μικρό βαθμό τα χαρακτηριστικά του VCO αλλά και δίνοντας την δυνατότητα παραμετροποίησης των χαρακτηριστικών ποιοτικών στοιχείων του τελικού ταλαντωτή που προκύπτει. Το σύστημα του ταλαντωτή κατασκευάστηκε σε πλακέτα(PCB) με διακριτά στοιχεία τα οποία παρέχονταν από το Εργαστήριο Ηλεκτρονικών Εφαρμογών. Το σύστημα αυτό μπορεί να ανταποκριθεί στις ραγδαία αυξανόμενες απαιτήσεις απόδοσης των ταλαντωτών στις σημερινές εφαρμογές, όσο αφορά στον χαμηλό θόρυβο φάσης, την χαμηλή κατανάλωση, την μικρή πολυπλοκότητα στο σχεδιασμό, την μικρή επιφάνεια και την ευκολία στην ολοκλήρωση. / The present diploma thesis pertains the study, design, simulation and implementation of an oscillator system that reduces phase noise in virtually any given already existing voltage controlled oscillator (VCO). To achieve that the proposed technique borrows from the idea of the Phase Locked Loop and with just a few extra electronic components it enables the reduction of phase noise ,by affecting the core characteristic qualities of the employed VCO only by a small fraction, as well as the optimization of the specifications of the resulting oscillator. This oscillator system was manufactured on a printed circuit board and implemented with discrete components which were supplied by the Applied Electronics Lab. This system can measure up to the increasing performance demands for oscillators by todays applications in terms of low phase noise, low power consumption, small design complexity, small area and ease of integration.
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Anxiety and it's management during awake procedures in operating theatres : a survey and randomised controlled trialMarran, Jayne January 2010 (has links)
This study investigates the prevalence of peri-operative anxiety and the effective management of intra-operative anxiety during awake surgery. Plastic and vascular surgical patients were selected for the study as many procedures performed within these specialities are performed under local or regional anaesthesia. The study consists of two distinct stages. The first stage was a postal survey of patients (n=213) who had undergone awake plastic, renal access or carotid surgery up to two weeks previously, in order to determine retrospectively the prevalence of peri-operative anxiety. The second stage of the study was a randomised controlled trial of interventions for the effective management of intra-operative anxiety in patients (n=128) having undergone the same surgical procedures described in stage one. The interventions tested in stage two were handholding and an anxiety management package involving a relaxation technique and a procedural information leaflet, against a 'usual care' control. The findings from stage one of the study suggest that peri-operative anxiety prevalence is low, although unacceptable levels of anxiety are seen to elevate during the intra-operative phase. The RCT in stage two demonstrated that intra-operative anxiety was no more effectively managed by the interventions tested than by usual care alone. The validity and reliability of retrospective anxiety measurement was investigated by comparing anxiety scores from stage one with contemporaneous and post-hoc anxiety scores from stage two and found to be an accurate measure of anxiety experienced at the time of the event.
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Implications of plasticization on the properties of hot-melt extruded oral dosage formsSchilling, Sandra Ursula 27 May 2010 (has links)
The influence of plasticization and other formulation factors on the properties of hot-melt extruded dosage forms for the controlled release of water-soluble active compounds was investigated. Citric acid monohydrate was demonstrated to function as a solid-state plasticizer in hot-melt extruded Eudragit® RS PO tablets and in cast films when concentrations below the compatibility limit were employed. Melting of the organic acid and solubilization in the polymer during extrusion were necessary to observe the plasticizing effect. The release rate of diltiazem hydrochloride, used as a high-melting, water-soluble model drug, from melt extruded Eudragit® RS PO matrix tablets increased and became independent of the original drug particle size in the presence of citric acid monohydrate. Thermal analysis of physical mixtures demonstrated that citric acid promoted drug melting during extrusion by interaction and melting point depression. Diltiazem hydrochloride remained amorphous in the final dosage form, and leaching of citric acid monohydrate enhanced drug diffusion by increasing the matrix porosity. Delayed-release matrix pellets with particle sizes below one mm were prepared by hot-melt extrusion, and the influence of the matrix forming polymer and the type and level of plasticizer on the processibility and release properties was investigated. Pellets complied with the USP requirement for delayed release articles to release less than 10% drug at pH 1.2 after 2 hours when plasticized Eudragit® S100 was used as the release-controlling material. High levels of efficient plasticizers had to be employed to decrease the polymeric melt viscosity, increase the process yield and enable extrusion at moderate temperatures to avoid instabilities during processing and storage. The aqueous solubility of the plasticizer further impacted the drug release rate in acid. A novel application of hot-melt extrusion for the preparation of monolithic matrices comprising enteric coated particles was studied. The influence of the mechanical strength of the multiparticulates, pellet loading and nature of the hydrophilic carrier material on the preservation of the delayed-release properties after extrusion was investigated. Soft particles coated with brittle films remained intact when low-melting carriers that did not solubilize the enteric film during extrusion were used, and the dissolution profile was stable over one year. / text
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Design, development, and evaluation of a scalable micro perforated drug delivery device capable of long-term zero order releaseRastogi, Ashish 01 June 2010 (has links)
Chronic diseases can often be managed by constantly delivering therapeutic
amounts of drug for prolonged periods. A controlled release for extended duration
would replace the need for multiple and frequent dosing. Local drug release would
provide added benefit as a lower dose of drug at the target site will be needed as
opposed to higher doses required by whole body administration. This would provide
maximum efficacy with minimum side effects.
Nonetheless, a problem with the known implantable drug delivery devices is
that the delivery rate cannot be controlled, which leads to drug being released in an
unpredictable pattern resulting in poor therapeutic management of patients. This
dissertation is the result of development of an implantable drug delivery system that is
capable of long-term zero order local release of drugs. The device can be optimized to deliver any pharmaceutical agent for any time period up to several years maintaining a
controlled and desired rate.
Initially significant efforts were dedicated to the characterization,
biocompatibility, and loading capacity of nanoporous metal surfaces for controlled
release of drugs. The physical characterization of the nanoporous wafers using
Scanning electron microscropy (SEM) and atomic force microscopy techniques (AFM)
yielded 3.55 x 10⁴ nm³ of pore volume / μm² of wafer surface. In vitro drug release
study using 2 - octyl cyanoacrylate and methyl orange as the polymer-drug matrix was
conducted and after 7 days, 88.1 ± 5.0 % drug was released. However, the initial goal
to achieve zero order drug release rates for long periods of time was not achieved.
The search for a better delivery system led to the design of a perforated
microtube. The delivery system was designed and appropriate dimensions for the
device size and hole size were estimated. Polyimide microtubes in different sizes (125-1000 μm) were used. Micro holes with dimensions ranging from 20-600 μm were
fabricated on these tubes using photolithography, laser drilling, or manual drilling procedures.
Small molecules such as crystal violet, prednisolone, and ethinyl estradiol were
successfully loaded inside the tubes in powder or solution using manual filling or
capillary filling methods. A drug loading of 0.05 – 5.40 mg was achieved depending
on the tube size and the drug filling method used.
The delivery system in different dimensions was characterized by performing
in vitro release studies in phosphate buffered saline (pH 7.1-7.4) and in vitreous humor from the rabbit’s eye at 37.0 ± 1.0°C for up to four weeks. The number of holes was varied between 1 and 3. The tubes were loaded with crystal violet (CV) and ethinyl
estradiol (EE). Linear release rates with R²>0.9900 were obtained for all groups with
CV and EE. Release rates of 7.8±2.5, 16.2±5.5, and 22.5±6.0 ng/day for CV and
30.1±5.8 ng/day for EE were obtained for small tubes (30 μm hole diameter; 125 μm
tube diameter). For large tubes (362-542 μm hole diameter; 1000 μm tube diameter), a
release rate of 10.8±4.1, 15.8±4.8 and 22.1±6.7 μg/day was observed in vitro in PBS
and a release rate of 5.8±1.8 μg/day was observed ex vivo in vitreous humor.
The delivery system was also evaluated for its ability to produce a biologically
significant amounts in cells stably transfected with an estrogen receptor/luciferase
construct (T47D-KBluc cells). These cells are engineered to produce a constant
luminescent signal in proportion to drug exposure. The average luminescence of
1144.8±153.8 and 1219.9±127.7 RLU/day, (RLU = Relative Luminescence Units), yet again indicating the capability of the device for long-term zero order release.
The polyimide device was characterized for biocompatibility. An automated
goniometer was used to determine the contact angle for the device, which was found to
be 63.7±3.7degreees indicating that it is hydrophilic and favors cell attachment. In
addition, after 72 h incubation with mammalian cells (RAW 267.4), a high cell
distribution was observed on the device’s surface. The polyimide tubes were also
investigated for any signs of inflammation using inflammatory markers, TNF-α and
IL-1β. No significant levels of either TNF-α or IL-1β were detected in polyimide
device. The results indicated that polyimide tubes were biocompatible and did not produce an inflammatory response. / text
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SYNTHESIS AND CHARACTERIZATION OF POLYMERIC ANTIOXIDANT DELIVERY SYSTEMSWattamwar, Paritosh P. 01 January 2011 (has links)
Even though the role of oxidative stress in a variety of disease states is known, strategies to alleviate this oxidative stress by antioxidants have not been able to achieve clinical success. Particularly, treatment of oxidative stress by small molecule antioxidants has not received due attention because of the challenges associated with its delivery. Antioxidant polymers, where small molecule antioxidants are incorporated into the polymer backbone, are an emerging class of materials that can address some of these challenges.
In this work, biodegradable polymers incorporating phenolic antioxidants in the polymer backbone were synthesized. Antioxidant polymers were then characterized for their in vitro degradation, antioxidant release and their effect on oxidative stress levels (redox state) in the cells. Trolox, a water-soluble analogue of vitamin E, was polymerized to synthesize poly(trolox ester) with 100% antioxidant content which undergoes biodegradation to release trolox. Nanoparticles of poly(trolox ester) were able to suppress oxidative stress injury induced by metal nanoparticles in an in vitro cell injury model.
In another study, we polymerized polyphenolic antioxidants (e.g. curcumin, quercetin) using a modified non-free-radical polymerization poly(β-amino ester) chemistry. This synthesis scheme can be extended to all polyphenolic antioxidants and allows tuning of polymer degradation rate by choosing appropriate co-monomers from a large library of monomers available for β-amino ester chemistry. Poly(antioxidant β-amino esters) (PABAE) were synthesized and characterized for their degradation, cytotoxicity and antioxidant activity. PABAE degradation products suppressed oxidative stress levels in the cells confirming antioxidant activity of degradation products.
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REGENERATION OF DAMAGED GROWTH PLATE USING IGF-I PLASMID-RELEASING POROUS PLGA SCAFFOLDSRavi, Nirmal 01 January 2009 (has links)
Growth plate injuries account for 15-30% of long bone fractures in children. About 10% of these result in significant growth disturbances due to formation of a boney bar. If not treated correctly, this can lead to life-lasting consequences of limb length inequalities and angular deformities. Current treatments for growth plate injuries include removal of boney bar and insertion of fat, silicone, bone cement, etc.. This treatment y is inadequate, leaving almost half of these patients with continued deformities. This dissertation reports characterization of a DNA–containing porous poly(lactic-co-glycolic acid) (PLGA) scaffold system, chondrogenesis using insulin-like growth factor I (IGF-I) plasmid-releasing scaffolds in vitro, and in vivo testing of IGF-I plasmid-releasing scaffolds to regenerate growth plate . Controlled release of naked and DNA complexed with polyethylenimine (PEI) was achieved from porous PLGA scaffolds. PEI affected release of complexes from PLGA scaffolds, as PEI:DNA complexes were released at a lower rate compared to naked DNA encapsulated in low molecular weight (LMW) and high molecular weight PLGA scaffolds, as well as hydrophilic and hydrophobic PLGA scaffolds. Hydrophilicity and molecular weight of PLGA affected the release profiles of both naked DNA and PEI:DNA complexes from the scaffolds, as evidenced by later peak DNA and PEI:DNA release with increasing hydrophilicity and molecular weight. LMW hydrophilic PLGA scaffolds supported growth and chondrogenic differentiation of mesenchymal multipotent D1 cells, chondrocytes, and bone marrow cells (BMCs) in vitro. Culturing BMCs on IGF-I plasmid-encapsulated scaffolds resulted in elevated expression of IGF-I compared to blank scaffolds. Removal of boney bar and implantation of IGF-I plasmid-releasing LMW PLGA scaffolds in a rabbit model of growth plate injury resulted in some improvement of leg angular deformity compared to no scaffold implantation. Histological analysis of the newly developed cartilage showed growth plate-like columnar arrangement of chondrocytes in a defect that received IGF-I plasmid encapsulated scaffold, although the level of organization of newly formed cartilage was inferior to that of native growth plate. This appears to be the first report of the regeneration of growth plate-like structure without the use of stem cells in an animal model of physeal injury.
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Empirical Evaluations of Semantic Aspects in Software DevelopmentBlom, Martin January 2006 (has links)
<p>This thesis presents empirical research in the field of software development with a focus on handling semantic aspects. There is a general lack of empirical data in the field of software development. This makes it difficult for industry to choose an appropriate method for their particular needs. The lack of empirical data also makes it difficult to convey academic results to the industrial world.</p><p>This thesis tries to remedy this problem by presenting a number of empirical evaluations that have been conducted to evaluate some common approaches in the field of semantics handling. The evaluations have produced some interesting results, but their main contribution is the addition to the body of knowledge on how to perform empirical evaluations in software development. The evaluations presented in this thesis include a between-groups controlled experiment, industrial case studies and a full factorial design controlled experiment. The factorial design seems like the most promising approach to use when the number of factors that need to be controlled is high and the number of available test subjects is low. A factorial design has the power to evaluate more than one factor at a time and hence to gauge the effects from different factors on the output.</p><p>Another contribution of the thesis is the development of a method for handling semantic aspects in an industrial setting. A background investigation performed concludes that there seems to be a gap between what academia proposes and how industry handles semantics in the development process. The proposed method aims at bridging this gap. It is based on academic results but has reduced formalism to better suit industrial needs. The method is applicable in an industrial setting without interfering too much with the normal way of working, yet providing important benefits. This method is evaluated in the empirical studies along with other methods for handling semantics. In the area of semantic handling, further contributions of the thesis include a taxonomy for semantic handling methods as well as an improved understanding of the relation between semantic errors and the concept of contracts as a means of avoiding and handling these errors.</p>
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Stereoselective synthesis & application of enantioenriched main group α-haloalkyl organometal reagentsEmerson, Christopher R. 10 November 2011 (has links)
Sulfoxide-ligand exchange (SLE) and asymmetric halogen-metal exchange (AHME) processes were separately examined for the enantioselective synthesis of functionalized alpha-haloalkylmetal (carbenoid) reagents. Carbenoids derived from SLE were used to effect stereospecific reagent-controlled homologation (StReCH) of boronic esters and those generated via AHME were engaged in Darzens-type chemistry with aldehydes.
Abstract for Part 1.
Scalemic syn alpha-chloroalkylsulfoxides p-TolS(O)CHClR [R = allyl, (1,3-dioxolan-2-yl)methyl, proparygyl, and 2-(benzyloxy)ethyl] were prepared from the corresponding thioethers by Jackson-Ellman-Bolm catalytic enantioselective sulfoxidation [cat. VO(acac)₂, tert-leucinol derived chiral Schiff base ligand, aq. H₂O₂, CHCl₃; 76-80% yield, >98% ee] followed by non-racemizing chlorination mediated by N-chlorosuccinimide in the presence of potassium carbonate (84-86% yield, syn:anti ≥ 20:1). The corresponding anti diastereoisomers were accessed from their syn epimers by sodium hexamethyldisilazide mediated deprotonation (THF, –78 °C) followed by treatment with either CH₃OH or CD₃OD to yield alpha-[¹H] or alpha-[²H] isotopomers, respectively (88% yield, anti:syn ≥ 17:1). Allyl and (1,3- dioxan-2-yl)methyl substituted chlorosulfoxides reacted with R'Li (t-BuLi or PhLi, THF, –78 °C) to give the expected products of SLE [p-TolS(O)R' and LiCHClR or LiCDClR]; however, neither the benzylether nor propargyl substituted substrates gave wholly satisfactory results under the same reaction conditions. The functionalized carbenoid reagents so obtained, 1-chloro-3-butenyllithium and 1-chloro-2-(1,3- dioxolan-2-yl)ethyllithium, were applied to the StReCH of B-(2-chloropyrid-5-yl) pinacol boronate but only the latter gave acceptable yields of chain extended products. The anti alpha-[²H]-chlorosulfoxide dioxolanyl bearing carbenoid precursor gave superior results to the analogous syn or anti alpha-[¹H]-chlorosulfoxides for StReCH of the B-pyridyl boronate [79% conversion, ≥ 89% ee (99% stereofidelity), vs. ≤ 68% conversion for non-deuterated chlorosulfoxides]. The origin of this isotope effect was traced to a deleterious proton transfer pathway between the alpha- chloroalkyllithium reagent and its chlorosulfoxide precursor. Sequential double iterative StReCH of B-(2-chloropyrid-5-yl) pinacol boronate with two separate portions of (S)-1-[²H]-1-chloro-2-(1,3-dioxolan-2-yl)ethyllithium (generated via SLE with phenyllithium) followed by oxidative work-up (with KOOH) gave (1R,2R)-1,2- [²H]₂-2-(2-chloropyrid-5-yl)-1,2-bis[(1,3-dioxolan-2-yl)methyl]ethanol (40% yield, ≥ 98% ee, dr = 85:15). Substitution of the (R)-configured carbenoid for its antipode in the second StReCH stage above gave the unlike (1S,2R)-isomer of the same pyridylethanol derivative (49% yield, ≥ 98% ee, dr = 79:21). The unlike diastereoisomer was advanced to the trifluoroacetamide of (1R,2R)-1,2-[2H]2-1- amino-2-(2-chloropyrid-5-yl)cyclohex-4-ene (6 steps, 5% overall yield); the non- deuterated isotopomer of this compound was previously advanced to the analgesic alkaloid (–)-epibatidine by Corey and co-workers.
Abstract for Part 2.
Scalemic planar chiral N,N-dialkyl 2-iodoferrocene carboxamides envisioned as recyclable precursors to ferrocenyl metal reagents for AHME, were prepared from ferrocene carboxylic acid by a three step sequence of: acid chloride formation [(COCl)₂ and cat. DMF)], aminolysis (with R₂NH, R = Me, Et, i-Pr; 65- 80% yield over 2 steps), and sec-butyllithium/(–)-sparteine mediated enantioselective directed ortho-metallation (DoM) followed by iodinolysis (87% yield, ≥ 96% ee). Attempts to access more elaborate 5-substituted 2-iodoferrocene carboxamides via DoM/iodinolysis of ortho-substituted ferrocene carboxamides (Me, Ph, or SiMe₃ substituents) mostly failed; however, analogous trisubstituted ferrocene oxazolines could be synthesized. Treatment of N,N-diisopropyl 2-iodoferrocene carboxamide (298, ≥ 96% ee) with n-BuLi (THF, –78 °C) resulted in complete conversion to the corresponding lithioferrocene (327) via I/Li interchange; subsequent iodinolysis initiated reverse Li/I exchange and returned iodoferrocene 298 without diminished enantiomeric excess, establishing configurational stability for the lithiated ferrocene intermediate. Prochiral (RCHI₂) and racemic (RCHICl) geminal dihalide substrates for AHME studies were prepared by electrophilic quench of dihalomethylsodiums with either Ph(CH₂)₃I or Me₃SiCl (50-78% yield). Of the four dihalides so produced, only prochiral substrate Me₃SiCHI₂ engaged in I/Li exchange with scalemic lithioferrocene 327 resulting in regeneration of its precursor iodoferrocene 298 and the formation of a putative chiral carbenoid Me₃SiCHLiI. Trapping of the carbenoid with aldehydes RCHO (R = Ph, 4-MeOC₆H₄, Ph(CH₂)₂, c-C₆H₁₁) in the presence of Me₂AlCl gave the expected epoxysilane products (35-40% yield, cis:trans ≥ 2:1) but without discernable enantiomeric excess. Hypotheses to account for the apparent lack of stereoinduction in this AHME cycle are presented. Comparable experiments using analogous magnesiated ferrocenes failed to produce putative carbenoid species from the same set of geminal dihalide substrates. / Graduation date: 2012
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