RESUMO
Various structural elements of the Cinchona alkaloid dimers are interrogated to establish a structure-enantioselectivity relationship (SER) in three different halocyclization reactions. SER for chlorocyclizations of a 1,1-disubstituted alkenoic acid, a 1,1-disubstituted alkeneamide, and a trans-1,2-disubstituted alkeneamide showed variable sensitivities to linker rigidity and polarity, aspects of the alkaloid structure, and the presence of two or only one alkaloid side group defining the catalyst pocket. The conformational rigidity of the linker-ether connections was probed via DFT calculations on the methoxylated models, uncovering especially high barriers to ether rotation out of plane in the arene systems that include the pyridazine ring. These linkers are also found in the catalysts with the highest enantioinduction. The diversity of the SER results suggested that the three apparently analogous test reactions may proceed by significantly different mechanisms. Based on these findings, a stripped-down analogue of (DHQD)2PYDZ, termed "(trunc)2PYDZ", was designed, synthesized, and evaluated, showing modest but considerable asymmetric induction in the three test reactions, with the best performance on the 1,1-disubstituted alkeneamide cyclization. This first effort to map out the factors essential to effective stereocontrol and reaction promotion offers guidance for the simplified design and systematic refinement of new, selective organocatalysts.
RESUMO
BACKGROUND: To describe the clinical and histopathologic findings in a patient with bilateral Candida albicans endophthalmitis due to an infected deep venous thrombus. CASE: A 43-year-old patient with bilateral Candida albicans endophthalmitis due to an infected central venous thrombus. The patient's ophthalmology and hospital charts were reviewed. Histopathologic sections of the Candida albicans retinal granuloma were examined under light microscopy. OBSERVATIONS: Our patient had multiple blood cultures positive for Candida albicans owing to an infected subclavicular venous thrombosis. Bilateral Candida albicans endophthalmitis was diagnosed. Bilateral vitrectomy and membrane peeling for macular traction retinal detachments were performed. In the right eye, a large retinal granuloma was excised during surgery to adequately relieve traction on the macula. Vision improved in both eyes after surgery. Histopathologic findings revealed branching hyphae surrounded by giant cells, endothelial cell-lined vascular channels, and inflammatory cells. CONCLUSIONS: This is the first report of an infected deep venous thrombosis causing bilateral endogenous endophthalmitis. Appropriate management of these patients requires clear differentiation between endogenous chorioretinitis and endophthalmitis. Patients with documented fungemia should have a dilated fundus examination on a regular basis until complete clearance of the infection.
