Felix J. Baerlocher

Synthesis and antifungal and antibacterial bioactivity of cyclic diamines containing boronate esters

Novel N2B heterocycles (1–5) are formed from the reaction of ethylenediamine derivatives with 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (2-HC(O)C6H4Bpin; pin = 1,2-O2C2Me4). X-ray diffraction studies have been carried out on four examples and show that reactions are selective in giving the isomer where the least substituted amine coordinates to the Lewis-acidic boron atom. Reaction of 2-HC(O)C6H4Bpin with diethylenetriamine gave a heterocycle (6) with a pendant primary amine group, which reacts further with 2-pyridinecarboxaldehyde to give a potential ligand (7) for transition metals. All new compounds show considerable antifungal activity against Aspergillus niger and Aspergillus flavus and moderate antibacterial activity against Bacillus cereus.

Synthesis, Characterization, and Antifungal Activity of Boron-Containing Thiosemicarbazones

Addition of thiosemicarbazide, 4‐allylthiosemicarbazide, and 4‐phenylthiosemicarbazide to (formylphenyl)boronic acids affords a series of thiosemicarbazones containing boronic acids. Addition of 2‐formylphenylboronic acid to the thiosemicarbazides gave the corresponding cyclic 2,3,1‐benzodiazaborines. All new compounds have been investigated for potential antifungal activity.

New and More Potent Antifungal Disulfides

From a design principle described in an earlier paper, a new series of substituted aryl methyl disulfides have been prepared and tested against Aspergillus niger and Aspergillus flavus. Methyl p-nitrophenyl disulfide is more potent (by an order of magnitude) than the fungitoxic natural product (CH3SCH2S)2. With the present rationale in hand, one can anticipate which Polycarpamine is an effective antifungal agent.

Meta-analysis of drug-eluting balloon angioplasty and drug-eluting stent placement for infrainguinal peripheral arterial disease.

PURPOSE To perform a meta-analysis of randomized controlled trials (RCTs) of drug-eluting balloon (DEB) angioplasty and drug-eluting stents (DESs) for infrainguinal peripheral arterial disease. MATERIALS AND METHODS Systematic searches were performed for all relevant RCTs. RESULTS Eight RCTs for DEB angioplasty and 12 RCTs for a DES in peripheral arterial disease were identified. Meta-analysis demonstrated statistically significant superiority of DEB over plain balloon angioplasty of femoral-popliteal disease for late lumen loss, restenosis, and target lesion revascularization, with no benefit in major amputation or mortality. Statistically significant superiority of DEB over percutaneous transluminal angioplasty (PTA) was demonstrated for infrapopliteal disease for restenosis and target lesion revascularization. Drug-eluting stents showed statistically significant superiority over bare metal stents (BMSs) of femoral-popliteal disease for late lumen loss and restenosis, with no benefit in mortality or amputation. Drug-eluting stents showed statistically significant superiority over BMSs of infrapopliteal disease restenosis and target lesion revascularization, with no benefit in amputation or mortality. CONCLUSIONS Drug-eluting balloon angioplasty and DESs demonstrated superior outcomes compared to PTA and BMS, with no difference in amputation or mortality.

Optimizing disulfide fungitoxicity: Adjustment of hydrocarbon chain length

Previously identified classes of antifungal disulfides are modified by extending alkyl substituents. Although, the principal focus is on f -sulfone disulfides, one nitrophenyl alkyl disulfide and a pair of f -ester disulfides were also prepared and examined. Optimum fungitoxicity is associated with structures which have seven to ten carbon atoms in the form of unbranched chains and/or phenyl rings.

Antifungal Thiosulfonates: Potency with Some Selectivity

A series of thiosulfonates have been prepared and tested against Aspergillus niger and Aspergillus flavus. In general, the thiosulfonates are moderate antifungal agents—more potent than corresponding inactive disulfides and less potent than corresponding very active fungitoxic disulfides. Apair of thiosulfonates show high selectivity, each killing only one kind of fungus.

Synthesis, characterization and antifungal testing of 3,4-dihydropyrimidin-2(1H)-(thio)ones containing boronic acids and boronate esters

The addition of formylphenylboronic acid derivatives to thiourea and ethyl acetoacetate proceeds in the presence of an additional Lewis acid catalyst to give the corresponding 3,4-dihydropyrimidin-2(1H)-(thio)ones (Biginelli products) in moderate yield. Compounds were tested for antifungal activity against pure cultures of Aspergillus niger, Aspergillus flavus, Candida albicans and Saccharomyces cerevisiae but, unfortunately, none showed any appreciable activity.

Synthesis, Characterisation, and Antifungal Activities of Novel Benzodiazaborines

Eight new fluoro- and methoxy-substituted benzodiazaborines have been prepared by a simple condensation reaction in high-to-excellent yields. All new compounds have been characterised by several physical methods, including X-ray diffraction studies on three examples. All new compounds were examined for antifungal activities against five species of potentially pathogenic fungi (Aspergillus niger, Aspergillus fumigatus, Rhizoctonia solani, Verticillium albo-atrum, and Verticillium dahliae). While substitution of the aromatic group derived from the 2-formylphenylboronic acid group had an effect on bioactivities, substitution on the parent thioamide C(=S)NH2 group of the starting thiosemicarbazide greatly reduced activities.

Selected a,a'-Dimethyl Disulfides: Submicrogram Fungitoxins

Recently developed synthetic methodology has been exploited for the preparation of an assortment of α,α´-disubstituted disulfides including all three linkage isomeric types of α,α´-diester dimethyl disulfides. Two of the diesters are very powerful antifungal agents against Aspergillus niger and Aspergillus flavus. An α-ester α´-sulfone disulfide is the most powerful fungitoxin developed by this ongoing research effort.

Oxazoles XXII.* The Cobalt(ii) Coordination Chemistry of 2-(ortho-Anilinyl)-4,4-dimethyl-2-oxazoline: Syntheses, Properties, and Solid-State Structural Characterization

Ethanol solutions of the cobalt(ii) halides react with an excess of 2-(ortho-anilinyl)-4,4-dimethyl-2-oxazoline (1: i.e. 2-(2′-anilinyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole) to give isolable κ2-N,N′-bonded species of 1 in good to excellent yields. The complexes CoX2(1-κ2-N,N′)·(H2O) n have been isolated for X = Cl (2: n = 1/2), X = Br and I (3 and 4, respectively; n = 0); the solid-state structures (X-ray) are in accordance with those suggested by UV-visible spectroscopy and conductivity measurements (i.e. non-ionic complexes with a pseudo-tetrahedral coordination motif around Co). In contrast, reaction of excess 1 with Co(NCS)2 forms the octahedral (UV-visible, X-ray) bis-isothiocyanato complex Co(NCS-κ1-N′)2(1-κ2-N,N′)2 (5) with cis-oriented NCS groups and trans-disposed oxazolines. Calculations at the PM3(tm) level of theory suggest that this isomer is close in energy to the four other possible (gas-phase) isomers. Treatment of ethanol solutions of hydrated cobaltous nitrate with excess 1 yields a material analyzed as [Co(NO3)(1)(H2O)2](NO3) (6a) and a small amount (less than 1%) of a second complex (6b); the latter has been characterized (X-ray) as the hydrated octahedral complex [Co(NO3-κ1-O)(1-κ2-N,N′)2(OH2)](NO3). In this case, the nitrato and aqua groupings are located cis to one another and trans to the coordinated –NH2 groups. Complex 6a is surmised to have a [Co(NO3-κ2-O,O′)2(1-κ2-N,N′)(OH2)2]NO3 structure. Cobalt compounds 2–5 and 1 have also been screened for their antifungal properties against Aspergillus niger, Aspergillus flavus, Candida albicans, and Saccharomyces cerevisiae but were found to be inactive in this regard.