Heterophosphole und Metallkomplexe von Aminophosphonsäuren

Die vorliegende Arbeit stellt die Ergebnisse der Untersuchungen aus zwei Themengebieten vor. Der erste Teil der Arbeit widmet sich der Synthese sowie der Komplex- und Strukturchemie von (Amino)phosphin- und -phosphonsäuren. Anhand von mehr als 20 neuen Kristallstrukturen wurden erstmals systematisch die Koordinationseigenschaften von Vertretern dieser interessanten Verbindungsklasse untersucht. Im Mittelpunkt des Interesses bei der Analyse der Kristallstrukturen stand die Art und Weise der Koordination der Phosphinato- bzw. Phosphonatoliganden an das Metallzentrum sowie die Rolle der Wasserstoffbrückenbindungen bei der Ausbildung der Kristallstruktur. Das zweite behandelte Themengebiet der vorliegenden Dissertation stellt die Entwicklung und Optimierung von Synthesewegen zu chiralen und achiralen Heterophospholen, sowie die Untersuchung der Stereoselektivität der 1,2-Additionsreaktion an der Phosphor-Element-Doppelbindung dar

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Herstellung von Nukleinsaeuresonden zum Nachweis von Bakterien der Milchflora

Available from TIB Hannover: MA 6352 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

New anellated 4H-1,4,2-diazaphospholes

Five new anellated 4H-1,4,2-diazaphospholes including the first examples of chiral 4H-1,4,2-diazaphospholes with the (-)-menthyl substituent have been prepared by two main routes: Hantzsch type cyclocondensation of 4-phenyl-2-amino-1,3-thiazole with chloromethyl dichlorophosphine and 4+1 cyclocondensation of cycloimmonium salts derived from 4-phenyl-2-amino-1,3-thiazole and 2-aminopyridine with PCl3 and NEt3. The new compounds have been characterized by multinuclear (H-1, C-13, P-31) NMR spectroscopy. Controlled hydrolysis of 5-phenylthiazolo3,2-d]1,4,2]diazaphosphole 2a with two equivalents of water yields the corresponding zwitterionic phosphinate 9, the structure of which was elucidated by single crystal X-ray diffraction. The structure in the solid state is governed by strong N-H center dot center dot center dot O hydrogen bonding resulting in chains along the crystallographic a-axis. The chloroform molecules are integrated in the chains by weaker C-H center dot center dot center dot O bonds and C-Cl center dot center dot center dot C halogen bonds