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Limaol ist ein aus dem benthischen Dinoflagellaten Prorocentrum lima isoliertes C40-Polyketid mit auffälligen Strukturmerkmalen wie vier nicht-konjugierten exo-Methylengruppen im nördlichen Teil und einem chiralen Spiroketalkern. Diese Dissertation beschreibt die Synthese von Limaol. Aufgrund der Größe des Zielmoleküls wurde ein fragmentbasierter Ansatz gewählt. Retrosynthetisch wurde das Molekül in drei Bausteine von ungefähr gleicher Komplexität aufgeteilt, was eine konvergente Synthese ermöglichte. Das zentrale und das südliche Fragment wurden durch eine asymmetrische Allylierung vereinigt, welche entgegen der erwarteten Cram-Chelat-Selektivität verlief und eine Inversion der Stereochemie an C27 nötig machte. Das nördliche Trien-Fragment wurde durch eine Allyl-Alkenyl-Kreuzkupplung mit dem Rest des Zielmoleküls verbunden. Insgesamt wurden auf diese Weise 3,3 mg Limaol hergestellt. In dem Bestreben, die Materialausbeute für biologische Tests zu erhöhen, wurde eine Synthese der zweiten Generation entwickelt. Die größten Engpässe des ersten Ansatzes waren auf die ungünstige Sterik des Zentralfragments zurückzuführen. Ein Wechsel der Schutzgruppen verbesserte die Effizienz der neuen Route erheblich. Die Gesamtausbeute wurde gegenüber dem Ansatz der ersten Generation vervierfacht. Darüber hinaus erwies sich die überarbeitete Route als skalierbar und lieferte 277 mg Limaol in einem Durchgang.

Stephan Hess,1 Martin Dubach,2 Mirko Meboldt,1 Lukas Foggensteiner3 1Swiss Federal Institute of Technology in Zurich (ETH Zurich), Zurich, Switzerland; 2Peripal AG; 3University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomCorrespondence: Stephan HessSwiss Federal Institute of Technology in Zurich (ETH Zurich), Leonhardstrasse 21, Zurich CH 8092, SwitzerlandTel +41 44 632 48 62Email stehess@ethz.chIntroduction: It is estimated that there are currently over 3 million patients receiving dialysis treatment worldwide. With effective pre-dialysis counselling, a majority of patients choose the home-based therapy peritoneal dialysis (PD) but only approximately 11% of prevalent dialysis patients use this modality. Connection-assist devices can overcome the challenges posed by decreased manual dexterity and/or visual acuity, and can allow more patients to be treated with home-based therapies. As part of the CE marking authorization, a connection device has been evaluated for safety and ease of use in a usability study.Methods: Fifteen patients and nine carers volunteered in this study, ranging from 23 to 86 years in age and from 0.3 to 24 years in experience in the PD therapy. The operating cycle consisted of eight tasks, each having several handling steps. The data analysis focused on the task effectiveness and the subjects’ subjective feedback from the NASA task load index (N-TLX) questionnaire and semi-structured interviews.Results: Of 1248 handling steps performed in total, 38 use errors were observed and discussed with the subjects. This equates to 97% of all handling steps being performed safely and easily. In all six dimensions of the N-TLX, more than 50 percent of subjects rated the task load 50 points or less on the scale. Regarding the handling of the device, 13 of 15 of the patients and 8 of 9 of the carers gave positive feedback.Discussion: Safety and ease of use was demonstrated by evaluating task effectiveness (97% SU), interviews and N-TLX. Additionally the study provided valuable individual user feedback, which will inform the final design of the system for PD. The majority of patients and carers gave positive feedback regarding use and handling of this connection device. Innovative connection devices in general promise to reduce the barriers to using this home-based dialysis treatment.Keywords: patient safety, usability study, ease of use, connection-assist device, peritoneal dialysis, NASA Task Load Index

An enantioselective synthesis of diverse N4-Boc-protected α,α-disubstituted piperazin-2-ones and tetrahydropyrimidin-2-ones using the palladiumcatalyzed decarboxylative allylic alkylation reaction has been achieved., An enantioselective synthesis of diverse N4-Boc-protected α,α-disubstituted piperazin-2-ones using the palladium-catalyzed decarboxylative allylic alkylation reaction has been achieved. Using a chiral Pd-catalyst derived from an electron deficient PHOX ligand, chiral piperazinones are synthesized in high yields and enantioselectivity. The chiral piperazinone products can be deprotected and reduced to valuable gem-disubstituted piperazines. This reaction is further extended to enable the enantioselective synthesis of α,α-disubstituted tetrahydropyrimidin-2-ones, which are hydrolyzed into corresponding chiral β2,2-amino acids.

The Journal of Technology Transfer, 38 (2), ISSN:0892-9912, ISSN:1573-7047

Background: In the German Code of Social Law V in §5 (7), paragraph a, the text states: “Only patients may be treated with “dialysis in a center”, who need this type of dialysis due to their clinical picture. However, the reality looks quite different. Objectives: This drawback was the motivation for a need finding study to find approaches to lower the access limitation to the peritoneal dialysis (PD) therapy, the most common home dialysis modality. The need finding study was conducted using mobile eye tracking with experienced and novice dialysis patients. Methods: The dialysis patients were visited at home and accompanied in all therapy handling steps to gain insights of the user experience of PD from a first-person view. The data analysis was not limited to the single central therapy steps but included also the preparation phase and the therapy handling steps as a whole. Results: In total, eight possibilities could be identified which promise to facilitate the access to home dialysis like a waste handling and managing system or a novel PD furniture. The most promising was a controller for PD which increases the safety against use errors and the comfort for the patient. Conclusions: For many patients, the use of an auto-connect device could increase safety and ease of use for patients. In addition, it could enhance standardization of the therapy process. Based on the eye tracking results, feasibility was proven with a functional prototype and a start-up was initiated for the further development and market readiness of such a device, with the public launch targeted in 2018.

The mechanism and the distance dependence of the photoinduced oxidation of guanine in DNA duplexes containing a covalently attached, selectively intercalated acridine derivative as a hole injecting chromophore have been investigated by means of femtosecond time-resolved absorption spectroscopy. The observed steep distance dependence is caused not solely by a decrease in electronic coupling, but also by a concomitant increase in reorganization energy with increasing distance. Additional experiments were performed on the complex between an engineered ligand-binding protein and fluorescein. The results underline the value of time-resolved spectroscopy for the elucidation of excited-state quenching mechanisms in complex biological systems. Der Mechanismus und die Reichweite der photoinduzierten Guanin-Oxidation in DNA-Doppelsträngen mit einem kovalent gebundenen, selektiv interkalierten Acridin-Derivat als Ladungsinjektor wurde mittels femtosekunden-zeitaufgelöster Absorptionsspektroskopie untersucht. Die beobachtete starke Distanzabhängigkeit konnte im Rahmen der Elektrontransfertheorie erklärt und auf Beiträge der elektronischen Kopplung und insbesondere der Reorganisationsenergie zurückgeführt werden. Zusätzliche Experimente an einem Komplex zwischen einem künstlichen Ligandenbindungsprotein und Fluoreszein unterstreichen die Bedeutung der zeitaufgelösten Spektroskopie für die Aufklärung von Fluoreszenzlöschungs-Mechanismen in komplexen biologischen Systemen.

Introduction: It is estimated that there are currently over 3 million patients receiving dialysis treatment worldwide. With effective pre-dialysis counselling, a majority of patients choose the home-based therapy peritoneal dialysis (PD) but only approximately 11% of prevalent dialysis patients use this modality. Connection-assist devices can overcome the challenges posed by decreased manual dexterity and/or visual acuity, and can allow more patients to be treated with home-based therapies. As part of the CE marking authorization, a connection device has been evaluated for safety and ease of use in a usability study. Methods: Fifteen patients and nine carers volunteered in this study, ranging from 23 to 86 years in age and from 0.3 to 24 years in experience in the PD therapy. The operating cycle consisted of eight tasks, each having several handling steps. The data analysis focused on the task effectiveness and the subjects’ subjective feedback from the NASA task load index (N-TLX) questionnaire and semi-structured interviews. Results: Of 1248 handling steps performed in total, 38 use errors were observed and discussed with the subjects. This equates to 97% of all handling steps being performed safely and easily. In all six dimensions of the N-TLX, more than 50 percent of subjects rated the task load 50 points or less on the scale. Regarding the handling of the device, 13 of 15 of the patients and 8 of 9 of the carers gave positive feedback. Discussion: Safety and ease of use was demonstrated by evaluating task effectiveness (97% SU), interviews and N-TLX. Additionally the study provided valuable individual user feedback, which will inform the final design of the system for PD. The majority of patients and carers gave positive feedback regarding use and handling of this connection device. Innovative connection devices in general promise to reduce the barriers to using this home-based dialysis treatment., Patient Preference and Adherence, 13, ISSN:1177-889X