Heterogeneous-phase Sonogashira cross-coupling reaction on COC surface for the grafting of biomolecules - Application to isatin.

The grafting of 5-iodoisatin heterocycle on a cyclic olefin copolymer (COC) and a gold surface was performed using a heterogeneous phase Sonogashira reaction consisting of coupling 5-iodoisatin with an arylalkyne previously introduced onto the surfaces. This optimized strategy takes advantage of the well-established methodology to functionalize COC or gold surfaces using aryldiazonium surface chemistry. Herein, we reported the first example of an isatin decorated polymeric or metallic surface. The surfaces were analyzed with a combination of techniques such as IR (Infrared spectroscopy), XPS (X-Ray photoelectron spectroscopy) and SPR (surface plasmon resonance). Docking studies showed that isatin and two derivatives interact with AmiC, a dimeric protein produced by Pseudomonas aeruginosa. Bacterial adhesion on isatin-COC platform was also observed. This general strategy for robust surface functionalization represents an easy approach for patterning surfaces with compounds of biological interest, allowing access to a large panel of original biosensors.

Organocatalysed synthesis of isoxazolines initiated by a chemoselective oxa-Michael reaction of N-BocNHOH.

An organocatalysed and chemoselective one-pot oxa-Michael-cyclocondensation reaction of N-BocNHOH to unsaturated α-ketoesters is reported which affords an original entry to enantioenriched 3-isoxazoline carboxylate derivatives as biorelevant heterocyclic frameworks.

Intramolecular photochemical dioxenone-alkene [2 + 2] cycloadditions as an approach to the bicyclo[2.1.1]hexane moiety of solanoeclepin A.

A synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes, was approached via an intramolecular [2 + 2] photocycloaddition. Aldehyde 12 containing the dioxenone chromophore served as a useful starting material, allowing the synthesis of a variety of photocycloaddition substrates via Grignard addition or via a Nozaki-Hiyama-Kishi reaction. Photolysis of the unsubstituted alkene 14 led to the expected crossed cycloadduct bicyclo[2.1.1]hexane 15 according to the so-called rule of five. However, several functionalized alkenes 18, 20, and 31 exhibited a complete reversal of cycloaddition regioselectivity, providing straight cycloadducts bicyclo[2.2.0]hexanes 21-26 and 4, respectively. Their structures were proved by a combination of extensive NMR measurements, X-ray analyses, and subsequent retro-aldol reactions. The latter de Mayo process allowed the formation of spiro-[3.5]nonane 35 and spiro[3.4]octane 36 as well as the cyclobutanes 37 and 38. Finally, the cyclization of the more rigid lactone precursor 28 occurred in high yield in the desired fashion with complete regio- and stereoselectivity to give 3 containing the core bicyclo[2.1.1]hexane skeleton of the natural product.

Morphologic and phenotypic heterogeneity of two cases of translocation t(4;11) acute leukemia.

The morphological, ultrastructural, and immunological characteristics of two cases of acute leukemia with t(4;11) (q21;q23) were studied. The blasts from both cases were initially classified as L1 lymphoblasts. Ultrastructural examination indicated a heterogenous blast population in both cases, with some regular lymphoblast-like cells, and others exhibiting nuclear irregularity, small bundles of microfilaments, or large inclusions. In one case at diagnosis, fresh cells expressed B-associated and a myeloid antigen (B4 and 1G10). At the second relapse, the cells from this patient expressed another myeloid-associated antigen, LFA1 molecule, recognized by the monoclonal antibody M232 (CD18). At the end of clinical evolution, a further myeloid antigen was expressed (OKM1), while 8% peroxidase were noted. The other case was studied at diagnosis only and did not express any myeloid marker but expressed the B-associated B4 antigen. Furthermore, the case that exhibited a phenotypic transformation, was noted to show a chromosomal clonal evolution not described so far in other reported cases of t(4;11) acute leukemia. A dual lymphoid-myeloid nature of t(4;11) acute leukemia has been widely discussed. One of the cases reported here supports this hypothesis while the other does not. We would like to underline the possibility of heterogeneity of a case at presentation and transformation to a myeloid phenotype through clonal evolution.

[Acute or subacute myelofibrosis]. / Les myélofibroses aiguës ou subaiguës

Nine patients were selected according to the following criteria: 1. Hematological findings consistent with the diagnosis of myelofibrosis with myeloid metaplasia (MMM), except for an excess of blasts in the blood and bone marrow; 2. No previous (silent) phase of MMM. 3. No PH1 chromosome, and 4. No identifiable cause of secondary myelofibrosis. These patients had either an acute or subacute myelofibrosis. The onset of such symptoms as fever, bone pain, hemorrhage and mild splenomegaly was rapid. Terminal acute leukemia or more often progressive bone marrow biopsy showing myelofibrosis with persistence of differentiated myeloid tissue, particularly megacaryocytes. Isotopic studies (59Fe and 51Cr) showed splenic erythroid metaplasia, poor bone marrow 59Fe uptake and increased peripheral red blood cell destruction. This study confirms that malignant myelosclerosis is a well-defined syndrome which must be distinguished from: a) Acute transformation of typical agnogenic myeloid metaplasia even though it was previously undiagnosed (4 cases of MMM illustrating this possibility have been reported); b) Acute myeloblastic leukemia with myelofibrosis; and c) Myelofibrosis secondary to lymphomatous or carcinomatous bone-marrow invasion (2 cases with acute myelofibrosis appearing long after appropriate treatment have been reported).