Chiral Amino Acids: A Versatile Tool in the Synthesis of Pharmaceuticals and Fine Chemicals

Methods of preparing enantiomerically pure amino acids especially focusing on amino-acylase-based resolution of D,L-acetylamino-acid precursors, synthesis of D-amino acids using a hydantoinase system, and the cofactor-dependent enzymatic reductive amination of α-keto acids to L-amino acids are described. Examples are given for bulk actives, based on L- and D-amino acids and peptides. L- and D-Tle (= L-/D-2-amino-3,3-dimethylbutanoic acid) are important molecules for synthesizing drugs and a great variety of chiral auxiliaries. A new chromatographic separation of bulky side-chain amino acids in a preparative scale is described, giving both enantiomers in >99% ee

Neue Synthese von Aminosäuren aus Halogencarbonsäureestern

Wir fanden, daß Halogencarbonsäureester mit Alkalimetallcyanaten in Gegenwart von Alkoholen mit guten Ausbeuten Aminosäuren ergeben. Ähnlich wie bei der Gabriel-Synthese wird eine geschützte Aminofunktion eingeführt - jedoch auf einfacherem und billigerem Weg - deren Schutzgruppe sich außerdem unter milderen Bedingungen rückstandsfrei abspalten läßt. Vereinzelt wurde die Umsetzung von Alkalimetallcyanaten mit Alkylhalogeniden und Alkoholen zu Urethanen schon beschrieben

L-Tryptophan Production by Auxotrophic and Analogue Resistant Mutants of Aureobacterium flavescens

A number of tyrosine plus phenylalanine double auxotrophic mutants were isolated by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) treatment of a locally isolated strain of Aureobacterium flavescens of which 11A39 and 11A17 were selected on the basis of their tryptophan production in a mineral salt medium over other isolated mutant strains. The mutational block in the aromatic amino acid biosynthetic pathway of the selected double auxotrophs were determined. By controlling pH of the production medium to near neutrality, the active growth period could be extended up to 72 h and more tryptophan was accumulated compared to pH unregulated culture where the active growth ceased after 48 h. Further improvement of the tryptophan production has been achieved by stepwise isolation of a mutant strain resistant to the tryptophan analogues p-fluorotryptophan (FT) and 5-methyl tryptophan (MT) from the 11A39. Demand for L-tryptophan as food additive and therapeutic agent is increasing day by day throughout the World, particularly in the underdeveloped and developing countries like India. Still to date India depends on other countries for L-tryptophan. The aim of this work is to develop a potent high yielding, feed back insensitive mutant strain and optimization of its medium pH for maximum production of tryptophan

Treatment of HIV-related primary central nervous system lymphoma with azt high dose, HAART, interleukin-2 and foscarnet in three patients

<p>Abstract</p> <p>Purpose</p> <p>Combined immunomodulatory and antiviral treatment was administered to three patients with newly diagnosed HIV-associated primary central nervous system lymphoma (PCNSL) in an attempt to improve outcomes.</p> <p>Patients and methods</p> <p>Three patients from our institution who were recently diagnosed with HIV-associated PCNSL received intravenous azidothymidine (AZT) 1.6 gr. bid for two weeks, followed by oral AZT 250 mg bid from day 15. In addition, complementary highly active antiretroviral therapy (HAART) with a second nucleoside reverse transcriptase inhibitor (NRTI) plus one protease inhibitor (PI) and interleukin 2 (IL-2) subcutaneously 2 million units twice daily (bid) plus foscarnet 90 mg/kg bid were administered on days 1-14. One patient received anti-EpsteinBarr virus (EBV)-maintenance therapy with ganciclovir, followed by cidofovir <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p> <p>Results</p> <p>All patients experienced progressive disease while on induction therapy, and switched early to whole-brain radiation therapy (WBRT) as second linetreatment. No grade 3 or 4 toxicities were observed. Two patients died on days 50 and 166 respectively due to progressive disease. The third patient with histologically proven lymphoproliferation and only suspected PCNSL remained alive at 53 months. He was on HAART and remained clinically and neurologically stable.</p> <p>Conclusion</p> <p>Although IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related conditions, they did not demonstrate benefit in lymphoma remission for 2 HIVassociated PCNSL patients. The third patient went into delayed remission after additional radiotherapy and was in good clinical and neurological health status over 53 months after diagnosis.</p

Bridging granularity gaps to decarbonize large-scale energy systems - The case of power system planning

The comprehensive evaluation of strategies for decarbonizing large- scale energy systems requires insights from many different perspectives. In energy systems analysis, optimization models are widely used for this purpose. However, they are limited in incorporating all crucial aspects of such a complex system to be sustainably transformed. Hence, they differ in terms of their spatial, temporal, technological, and economic perspective and either have a narrow focus with high resolution or a broad scope with little detail. Against this background, we introduce the so- called granularity gaps and discuss two possibilities to address them: increasing the resolutions of the established optimization models, and the different kinds of model coupling. After laying out open challenges, we propose a novel framework to design power systems in particular. Our exemplary concept exploits the capabilities of power system optimization, transmission network simulation, distribution grid planning, and agent- based simulation. This integrated framework can serve to study the energy transition with greater comprehensibility and may be a blueprint for similar multi-model analyses

Analyse der Integration erneuerbarer Energien in Deutschland und Europa unter Berücksichtigung der Versorgungssicherheit und dezentraler Flexibilitäten

Das Vorhaben greift den Forschungsbedarf auf, der aus dem vorangehenden Vorhaben INTEEVER (FKZ 03ET4020) hervorgegangen ist. Dieser betrifft zum einen den Grad der Genauigkeit und der Differenzierung der modelltechnischen Abbildung von Verbrauchern und Erzeugern im deutschen und europäischen Stromsystem und damit insbesondere die Modelleingangsdaten, die einen relevanten Einfluss auf die Ergebnisse haben. Zum anderen wird eine enge Kopplung von Energiesystemmodellierung und Leistungsflusssimulation im europäischen Verbundnetz angestrebt