Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
J Org Chem ; 83(11): 5954-5968, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29717607

ABSTRACT

A general protocol is described for inducing enantioselective halolactonizations of unsaturated carboxylic acids using novel bifunctional organic catalysts derived from a chiral binaphthalene scaffold. Bromo- and iodolactonization reactions of diversely substituted, unsaturated carboxylic acids proceed with high degrees of enantioselectivity, regioselectivity, and diastereoselectivity. Notably, these BINOL-derived catalysts are the first to induce the bromo- and iodolactonizations of 5-alkyl-4( Z)-olefinic acids via 5- exo mode cyclizations to give lactones in which new carbon-halogen bonds are created at a stereogenic center with high diastereo- and enantioselectivities. Iodolactonizations of 6-substituted-5( Z)-olefinic acids also occur via 6- exo cyclizations to provide δ-lactones with excellent enantioselectivities. Several notable applications of this halolactonization methodology were developed for desymmetrization, kinetic resolution, and epoxidation of Z-alkenes. The utility of these reactions is demonstrated by their application to a synthesis of precursors of the F-ring subunit of kibdelone C and to the shortest catalytic, enantioselective synthesis of (+)-disparlure reported to date.


Subject(s)
Lactones/chemistry , Naphthols/chemistry , Alkanes/chemical synthesis , Bromine/chemistry , Catalysis , Cyclization , Iodine/chemistry , Molecular Structure , Stereoisomerism , Xanthones/chemical synthesis
2.
Retina ; 37(1): 22-31, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27380429

ABSTRACT

BACKGROUND: The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease. METHODS: Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.25 mg) or 1400W (2 mg and 0.4 mg) in the left eye. Toxicity was assessed by slit-lamp and fundus examination, intraocular pressure and pachymetric measurements, and electrophysiologic and histologic analysis. RESULTS: Eyes injected with high doses of aminoguanidine (5 mg) or 1400W (2 mg) demonstrated severe retinal vascular attenuation and infarction. Lower doses of intravitreal aminoguanidine (1 mg) and 1400W (0.4 mg) caused no significant toxic ocular effects in rabbit eyes. CONCLUSION: If the difference in vitreal volume between rabbit eyes and human eyes is taken into account, aminoguanidine (2.7 mg) and 1400W (1 mg) would be reasonable intravitreal doses to test for safety and efficacy in early clinical trials.


Subject(s)
Amidines/toxicity , Benzylamines/toxicity , Diabetic Retinopathy/drug therapy , Enzyme Inhibitors/toxicity , Guanidines/toxicity , Nitric Oxide Synthase Type II/antagonists & inhibitors , Retina/drug effects , Amidines/administration & dosage , Amidines/therapeutic use , Animals , Aqueous Humor/metabolism , Benzylamines/administration & dosage , Benzylamines/therapeutic use , Diabetic Retinopathy/pathology , Disease Models, Animal , Electroretinography/drug effects , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Guanidines/administration & dosage , Guanidines/therapeutic use , Intraocular Pressure/drug effects , Intravitreal Injections/adverse effects , Male , Nitric Oxide/metabolism , Rabbits , Retina/pathology , Vitreous Body/drug effects , Vitreous Body/metabolism
3.
J Ocul Pharmacol Ther ; 32(7): 437-41, 2016 09.
Article in English | MEDLINE | ID: mdl-27414817

ABSTRACT

PURPOSE: The choice and route of antibiotic prophylaxis in the setting of open globe injury remains controversial. We investigated the utility of intravenous vancomycin and cefepime prophylaxis in preventing endopthalmitis after open globe injury. METHODS: The charts of 224 patients who presented to Parkland Memorial Hospital and Children's Medical Center in Dallas, Texas, between June 1, 2009 and June 30, 2013, with open globe injury and who were treated with prophylactic intravenous vancomycin and cefepime were retrospectively reviewed. Data collection included time from injury to presentation, mechanism of injury, details of ophthalmological examination, timing of open globe repair, and length of follow-up. All patients were treated with intravenous vancomycin and cefepime for 48 h after presentation. RESULTS: The primary outcome measure was rate of endophthalmitis, and the secondary outcome measure was identification of risk factors for developing endophthalmitis. Out of 224 patients who presented after open globe injury, 3 patients had signs of endophthalmitis on initial exam before starting antibiotics, and 2 patients developed endophthalmitis after initiation of vancomycin and cefepime (0.9%). Delayed time from injury to presentation was a risk factor for post-traumatic endophthalmitis (P = 0.0002). The association between presence of intraocular foreign body and post-traumatic endophthalmitis was approaching significance (P = 0.064). CONCLUSIONS: When intravenous vancomycin and cefepime are used prophylactically after open globe injury, the rate of endophthalmitis is low.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cephalosporins/therapeutic use , Endophthalmitis/drug therapy , Eye Infections, Bacterial/drug therapy , Eye Injuries, Penetrating/drug therapy , Vancomycin/therapeutic use , Administration, Intravenous , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Cefepime , Cephalosporins/administration & dosage , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Vancomycin/administration & dosage , Young Adult
4.
J Am Chem Soc ; 134(27): 11128-31, 2012 Jul 11.
Article in English | MEDLINE | ID: mdl-22726214

ABSTRACT

A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number of structurally distinct unsaturated acids. Like some known catalysts, this catalyst promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but it also catalyzes the highly enantioselective bromolactonizations of 5-alkyl-4(Z)-pentenoic acids. These reactions represent the first catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via 5-exo mode cyclizations to give lactones in which new carbon-bromine bonds are formed at a stereogenic center with high enantioselectivity. We also disclose the first catalytic desymmetrization of a prochiral dienoic acid by enantioselective bromolactonization.


Subject(s)
Alkenes/chemistry , Bromine/chemistry , Carboxylic Acids/chemistry , Lactones/chemistry , Catalysis , Halogenation , Naphthols/chemistry , Stereoisomerism
SELECTION OF CITATIONS
SEARCH DETAIL
...