Synthesis of Vicinal anti-Amino Alcohols from N-tert-Butanesulfinyl Aldimines and Cyclopropanols.

The stereoselective synthesis of vicinal amino alcohols derivatives from 1-substituted cyclopropanols and chiral N-tert-butanesulfinyl imines is described. Cyclopropanols are easily prepared from carboxylic esters upon reaction with ethylmagnesium bromide in the presence of titanium tetraisopropoxide and undergo carbon-carbon bond cleavage by means of diethylzinc to produce, upon base deprotonation, enolized zinc homoenolates, which react with chiral sulfinyl imines in a highly regio- and stereoselective manner.

Stabilized Palladium Nanoparticles from Bis-(N-benzoylthiourea) Derived-PdII Complexes as Efficient Catalysts for Sustainable Cross-Coupling Reactions in Water.

Stable palladium (II) complexes, incorporating a double (N-benzoylthiourea) arrangement bonded to a complex heterocyclic scaffold, are used as precursors of catalytic species able to promote Suzuki-Miyaura, Mizoroki-Heck, Hiyama, Buchwald-Hartwig, Hirao and Sonogashira-Hagihara cross-coupling transformations in water. These sustainable processes are chemoselective and very versatile. The nanoparticles responsible for these catalytic reactions were analyzed and studied. Their usefulness is demonstrated after several tests and analyses. The heterogeneous character of this species in water was also confirmed.

Nms-Amides: An Amine Protecting Group with Unique Stability and Selectivity.

p-Toluenesulfonyl (Tosyl) and nitrobenzenesulfonyl (Nosyl) are two of the most common sulfonyl protecting groups for amines in contemporary organic synthesis. While p-toluenesulfonamides are known for their high stability/robustness, their use in multistep synthesis is plagued by difficult removal. Nitrobenzenesulfonamides, on the other hand, are easily cleaved but display limited stability to various reaction conditions. In an effort to resolve this predicament, we herein present a new sulfonamide protecting group, which we term Nms. Initially developed through in silico studies, Nms-amides overcome these previous limitations and leave no room for compromise. We have investigated the incorporation, robustness and cleavability of this group and found it to be superior to traditional sulfonamide protecting groups in a broad range of case studies.

Pseudo-multicomponent 1,3-dipolar cycloaddition involving metal-free generation of unactivated azomethine ylides.

The pseudo-multicomponent reaction between propargyl amine, an aldehyde and an electron-deficient alkene is described. The C-H activation takes place thermally and allows the obtaining of cycloadducts in very good yields with high diastereoselectivities. The relative configuration is determined by X-ray diffraction analysis of the chiral molecule, obtained as a single diastereoisomer, using a chiral maleimide. A brief study of the stability of the possible ylides involved in the process is also mentioned, confirming the high diastereoselectivity observed. The high functional group density of these cycloadducts permits the synthesis of complex heterocycles. After allylation or propargylation of the pyrrolidine nitrogen atom, RCM-DA cycloaddition or cyclotrimerization with an alkyne is studied, respectively. In this last example, the resulting tetracyclic structures are of potential interest as drugs for the treatment of cystic fibrosis.

Stereoselective Synthesis of 1-Substituted Homotropanones, including Natural Alkaloid (-)-Adaline.

The stereocontrolled synthesis of 1-substituted homotropanones, using chiral N-tert-butanesulfinyl imines as reaction intermediates, is described. The reaction of organolithium and Grignard reagents with hydroxy Weinreb amides, chemoselective N-tert-butanesulfinyl aldimine formation from keto aldehydes, decarboxylative Mannich reaction with ß-keto acids of these aldimines, and organocatalyzed L-proline intramolecular Mannich cyclization are key steps of this methodology. The utility of the method was demonstrated with a synthesis of the natural product (-)-adaline, and its enantiomer, (+)-adaline.

Free Amino Group Transfer via α-Amination of Native Carbonyls.

We report herein a straightforward transfer of a free amino group (NH2 ) from a commercially available nitrogen source to unfunctionalized, native carbonyls (amides and ketones) resulting in direct α-amination. Primary α-amino carbonyls are readily produced under mild conditions, further enabling diverse in situ functionalization reactions-including peptide coupling and Pictet-Spengler cyclization-that capitalize on the presence of the unprotected primary amine.

Stereoselective Synthesis of δ- and ε-Amino Ketone Derivatives from N-tert-Butanesulfinyl Aldimines and Functionalized Organolithium Compounds.

The addition of functionalized organolithium compounds derived from 5-chloro-2-methoxy-1-pentene and 6-chloro-2-methoxy-1-hexene to N-tert-butanesulfinyl aldimines imines, and a subsequent hydrolysis of the enol ether moiety, yielded different δ- and ε-amino ketone derivatives, respectively, in moderate yields and diastereoselectivities. The application of these compounds in organic synthesis was demonstrated by the preparation of 2-substituted 6-methylpiperidines in a stereoselective manner, among them natural alkaloids (+)- and (-)-isosolenopsin A.

Synthesis of Chiral 1,3-Dienes through Ring-Closing Metathesis of Enantioenriched Enynes: Potential Precursors of Morphane Analogs.

A simple methodology for the synthesis of enynes by indium mediated diastereoselective allylation of aromatic N-tert-butanesulfinylimines bearing alkenyl groups at ortho-position with allyl bromide has been developed. The addition of the allyl indium intermediate to the chiral imine took place with excellent diastereoselectivity. Ruthenium-catalyzed ring-closing metathesis of the resulting enynes provided the expected cyclic 1,3-dienes in good to moderate yields. These chiral dienes are potential precursors of biologically and pharmacologically active morphane derivatives.

Renal artery occlusion in autosomal dominant polycystic kidney disease.

Several vascular abnormalities have been reported in autosomal dominant polycystic kidney disease (ADPKD). Occlusion of the renal artery is uncommon in ADPKD and can be associated with hypertension. We report a 38-year-old woman with ADPKD and severe hypertension, abdominal magnetic resonance angiogram and arteriography revealed left renal artery total occlusion. A revascularization approach was not considered feasible and she was given conservative treatment. We review the literature and make some comments about renal artery occlusion in ADPKD. This association should be kept in mind in cases of ADPKD with severe or resistant hypertension.

Three-Component 1,2-Carboamidation of Bridged Bicyclic Alkenes via RhIII-Catalyzed Addition of C-H Bonds and Amidating Reagents.

A three-component method is described for the preparation of syn-1,2-disubstituted bridged bicyclic compounds. The reaction was demonstrated for readily available aromatic and heteroaromatic C-H bond substrates with tertiary and secondary amide, lactam, pyrazole, and triazole directing groups and a variety of bridged bicyclic alkenes, including norbornene, benzonorbornadiene, oxygen- and nitrogen-bridged analogs, and an unsaturated tropinone. A broad dioxazolone scope was also observed. The use of a chiral Cp-derived RhIII catalyst enables asymmetric synthesis of products.

Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease.

BACKGROUND: Mast cells (MCs) might play a pathogenetic role in renal fibrosis. Tryptase is a marker for activated MCs. Little is known about tryptase levels in the chronic renal disease population. METHODS: We examined serum MC tryptase concentrations in relation to specific laboratory abnormalities in 153 outpatients with chronic kidney disease (CKD) and in 35 hemodialysis (HD) patients. RESULTS: Here we found that tryptase mean values were higher in men than in women (12.4 +/- 7.6 microg/L vs. 10.2 +/- 8.4 microg/L; p<0.05). Tryptase levels were increased in CKD stages 4 and 5 and in HD patients, versus CKD stages 1 and 2: 12.7 +/- 7.3 microg/L, 13.8 +/- 7.8 microg/L, 15 +/- 8.9 microg/L vs. 6.7 +/- 5.1 microg/L (p<0.01). In univariate analysis, in the conservative treatment CKD population, tryptase was positively correlated with urea, creatinine, potassium, uric acid, phosphorus, parathyroid hormone, homocysteine, fibrinogen and proteinuria (p<0.01); tryptase was negatively correlated with calcium, albumin, creatinine clearance, estimated glomerular filtration rate (by abbreviated MDRD equation) and urine creatinine (p<0.01). In HD patients, the only significative correlation found was with systolic blood pressure and diastolic blood pressure (p<0.01). No significant correlations were found between tryptase and other parameters such as albumin, glucose, hemoglobin, leukocytes, immunoglobulins or C-reactive protein. Multiple regression analysis showed estimated glomerular filtration rate and proteinuria to be independent determinants of tryptase. CONCLUSIONS: This is the first study to determine that tryptase levels increase with higher degrees of kidney dysfunction. The association with markers of diminished renal function suggests impaired metabolism or a negative effect of inflammation on glomerular filtration rate. Further studies are required to ascertain the clinical implications of these findings.

Acute tubulointerstitial nephritis and polyclonal hypergammaglobulinaemia: Which is the culprit?

Proton pump inhibitors (PPIs) are among the most frequent implicated drugs in acute tubulointerstitial nephritis (ATIN), nevertheless it is important to report cases with atypical profiles. A 80-year-old female, exposed during 34 months to omeprazole, presented with polyclonal hypergammaglobulinaemia and renal failure. After stopping omeprazole there was a partial improvement in serum creatinine and IgG. Renal biopsy revealed ATIN; immunohistochemistry for IgG4 was negative. Treatment with steroids and mycophenolate sodium improved renal function and normalized immunoglobulins. The lack of data of other entities and the patient's evolution strongly point omeprazole as the culprit. After 27 months of follow-up, she remains clinical and analytically stable. ATIN caused by PPIs may appear after a long period of exposure and may be accompanied by analytical anomalies that simulate a systemic disease.

Primary hyperaldosteronism associated with vitiligo vulgaris and autoimmune hypothyroidism.

Type 3 polyendocrine autoimmune syndrome (PAS) is defined as the association between an autoimmune thyroid disease and 1 or more other autoimmune diseases, except for autoimmune Addison disease or hypoparathyroidism. Here we report an extremely rare case of type 3 PAS in which vitiligo vulgaris and symptomless autoimmune hypothyroidism were observed during the study of primary hyperaldosteronism.

Selective palladium(ii)-mediated oxidation of homoallylic N-tert-butanesulfinyl amine derivatives.

The palladium(ii)-catalyzed oxidation of homoallylic amine derivatives resulting from the allylation of N-tert-butanesulfinyl imines with allyl bromide led to the formation of the corresponding terminal allylic acetates in a regioselective fashion in moderate yields. In the case of the homoallylic amine derivatives obtained using cyclohexenyl bromide as the allylating reagent, the allylic oxidation took place with high regio- and diastereoselectivity and yields ranging from 40 to 85%.

Crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis.

We describe the association of crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome. A 39-year-old woman presented edema and proteinuria and later a non-pruritic urticarial rash. Laboratory results showed nephrotic syndrome, hypocomplementemia and positive anti-C1q antibodies. Skin biopsy disclosed leukocytoclastic vasculitis. Acute renal failure developed. Renal biopsy revealed crescentic membranoproliferative glomerulonephritis. She was treated with corticosteroids and cyclosphosphamide with improvement of the renal function and partial remission of the nephrotic syndrome. Afterwards the nephrotic syndrome relapsed, mycophenolate mofetil in monotherapy was administered with reduction in proteinuria. As far as we know only 3 cases, 2 in children and one in an adult, of crescentic glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome have been reported. In our patient renal manifestations preceded urticarial lesions. We provide information on the evolution during a 42-month follow-up.

Membranoproliferative glomerulonephritis due to visceral leishmaniasis in an HIV patient.

BACKGROUND: Visceral leishmaniasis is an important opportunistic disease in HIV-positive patients. The information available on the effects of such co-infection in the kidney is limited. We describe a patient with HIV/leishmania coinfection who developed nephrotic syndrome and membranoproliferative glomerulonephritis. As far as we know, only 2 cases of this nephropathy in HIV/leishmania coinfection have been reported. CASE REPORT: A 47-year-old man developed nephrotic syndrome. He had been diagnosed with HIV infection and visceral leishmaniasis and was treated with antiretroviral therapy, antimonial compounds, liposomal amphotericin B and miltefosine, but the leishmania followed a relapsing course. Renal biopsy disclosed membranoproliferative glomerulonephritis and leishmania amastigotes were seen within glomerular capillary lumens. He was given miltefosine and liposomal amphotericin B but the leishmaniasis persisted. Stage 3B chronic renal disease and nephrotic range proteinuria tend to become stable by 15-month follow-up. CONCLUSIONS: Our case illustrated some aspects of leishmaniasis in HIV patients: its relapsing course, the difficulties in therapy, and the renal involvement.