Pinacol macrocyclization-based route to the polyfused medium-sized CDE ring system of lancifodilactone G

The polyfused medium-sized CDE ring system of lancifodilactone G is assembled via B-alkyl Suzuki-Miyaura cross-coupling and SmI 2-mediated pinacol macrocyclization as the key strategic steps.     

Rectifiable oscillations in second-order linear differential equations

We study the linear differential equation , on I=(0,1), where the coefficient f(x) is strictly positive and continuous on I, and satisfies the Hartman-Wintner condition at x=0. The four main results of the paper are: (i) a criterion for rectifiable oscillations of (P), characterized by the integrability of on I; (ii) a stability result for rectifiable and unrectifiable oscillations of (P), in terms of a perturbation on f(x); (iii) the s-dimensional fractal oscillations (for which we assume also f(x)∼cx−α when x→0, α>2, and s=max{1,3/2−2/α}); and (iv) the co-existence of rectifiable and unrectifiable oscillations in the absence of the Hartman-Wintner condition on f(x). Explicit examples related to the above results are given.     

Iron(III) amine-bis(phenolate) complexes as catalysts for the coupling of alkyl halides with aryl Grignard reagents

Catalytic cross-coupling of aryl Grignard reagents with primary and secondary alkyl halides bearing beta-hydrogens is achieved using Fe(III) amine-bis(phenolate) halide complexes.     

Bifunctional polymeric organocatalysts and their application in the cooperative catalysis of Morita-Baylis-Hillman reactions

A series of soluble, non-cross-linked polystyrene-supported triphenylphosphane and 4-dimethylaminopyridine reagents were prepared. Some of these polymeric reagents contained either alkyl alcohol or phenol groups on the polymer backbone. The use of these materials as organocatalysts in a range of Morita-Baylis-Hillman reactions indicated that hydroxyl groups could participate in the reactions and accelerate product formation. In the cases examined, phenol groups were more effective than alkyl alcohol groups for catalyzing the reactions. This article is one of the first reports of the synthesis and use of non-natural, bifunctional polymeric reagents for use in organic synthesis in which both functional groups can cooperatively participate in the catalysis of reactions.     

Microwave-assisted extraction of active pharmaceutical ingredient from solid dosage forms

The microwave assisted extraction (MAE) technique has been evaluated for the extraction of active pharmaceutical ingredients (API) from various solid dosage forms. Using immediate release tablets of Compound A as a model, optimization of the extraction method with regards to extraction solvent composition, extraction time and temperature was briefly discussed. Complete recovery of Compound A was achieved when samples were extracted using acetonitrile as the extraction solvent under microwave heating at a constant cell temperature of 50 degrees C for 5 min. The optimized MAE method was applied for content uniformity (single tablet extraction) and potency (multiple tablets extraction) assays of release and stability samples of two products of Compound A (5 and 25mg dose strength) stored at various conditions. To further demonstrate the applicability of MAE, the instrumental extraction conditions (50 degrees C for 5 min) were adopted for the extraction of montelukast sodium (Singulair) from various solid dosage forms using methanol-water (75:25, v/v) as the extraction solvent. The MAE procedure demonstrated an extraction efficiency of 97.4-101.9% label claim with the greatest RSD at 1.4%. The results compare favorably with 97.6-102.3% label claim with the greatest RSD at 2.9% obtained with validated mechanical extraction procedures. The system is affordable, user-friendly and simple to operate and troubleshoot. Rapid extraction process (7 min/run) along with high throughput capacity (up to 23 samples simultaneously) would lead to reduced cycle time and thus increased productivity.     

MRI of blood volume with superparamagnetic iron in choroidal melanoma treated with thermotherapy

Functional magnetic resonance imaging (MRI) with a new intravascular contrast agent, monocrystalline iron oxide nanoparticles (MION), was applied to assess the effect of transpupillary thermotherapy in a rabbit model of choroidal melanoma. 3D-spoiled gradient recalled sequences were used for quantitative assessment of blood volume. The MRI-parameters were 5/22/35 degrees (time of repetition (TR)/echo delay (TE)/flip angle (FA)) for T(1)- and 50/61/10 degrees for T(2)-weighted sequences. Images were collected before and at different times after MION injection. In all untreated tissues studied, MION reduced the T(2)-weighted signal intensity within 0.5 h and at 24 h (all p <== 0.012), whereas no significant changes were detected in treated tumors. T(1)-weighted images also revealed differences of MION-related signal changes between treated tumors and other tissues, yet at lower sensitivity and specificity than T(2). The change of T(2)-weighted MRI signal caused by intravascular MION allows early distinction of laser-treated experimental melanomas from untreated tissues. Further study is necessary to determine whether MRI can localize areas of tumor regrowth within tumors treated incompletely.     

An efficient palladium-benzimidazolyl phosphine complex for the Suzuki-Miyaura coupling of aryl mesylates: facile ligand synthesis and metal complex characterization

A new class of easily accessible hemilabile benzimidazolyl phosphine ligands has been developed. The ligand skeleton is prepared from commercially available and inexpensive o-phenylenediamine and 2-bromobenzoic acid. With catalyst loading down to 0.5 mol% palladium, excellent catalytic activity towards the Suzuki-Miyaura coupling of aryl mesylates is still observed. This represents the lowest catalyst loading achieved so far for this reaction in general. X-Ray crystallography shows that new ligand L2 is coordinated with Pd in a κ(2)-P,N fashion.     

Crystal structure of a non-stoichiometric channel inclusion complex of 1-benzyl-6-phenylpiperidin-2-one-5-carboxylic acid with acetonitrile

C₁₉H₁₉NO₃·x CH₃CN (x=0.3),M _r=643.35, hexagonal, space groupP6₁ (No. 169),a=23.027(5),c=5.775(1) Å,V=2652(1) ų,Z=6. The structure was solved by direct methods and refined toR=0.077 for 1562 observed MoK reflections. The title heterocyclic carboxylic acid was established as thetrans isomer, with the phenyl and carboxyl substituents occupying pseudo-equatorial and equatorial positions, respectively, of the piperidin-2-one ring in a half-chair conformation. Acid host molecules related by the 6₁ screw operation are linked by intermolecular O–H...O (cyclic amide) hydrogen bonds to generate an open channel bounded by coaxial intertwined helices each having a pitch of 5c. Within each channel of free diameterca. 6.0 Å the acetonitrile molecules partially occupy highly disordered sites which do not lie on thec axis. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82067 (13 pages).