Synthesis of 3-carbomethoxy-3,4-dialkylcyclohexanones

The uncatalyzed 1,4-addition of phenylmagnesium bromide and furylmagnesium iodide to methyl 5-methoxy-1,5-cyclohexadienylcarboxylate ($\text{1}$), directly followed by alkylation and hydrolysis leads to the corresponding cyclohexanones of type $\text{2}$ (R₁ and R₂ trans) in moderate to high yield.     

Multifunctional layer-by-layer coating of digitally encoded microparticles

In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick "multiplexing" assays. By making use of encoded microparticles, such assays allow simultaneous determination of the presence of several analytes in a biological sample. The microparticles under investigation in this study are encoded by writing a digital dot or bar code in their central plane. This study evaluates to what extent a "multifunctional" coating can be applied around the digitally encoded microparticles by the layer-by-layer (LbL) technology. We show that a LbL coating containing CrO2 nanoparticles allows (a) an optimal (optical) readout of the dot and bar codes, (b) a perfect orientation of the microparticles, necessary to be able to read the code, and (c) an optimal coupling of capture probes to the surface of the microparticles.     

Multivariate generalized S-estimators

In this paper we introduce generalized S-estimators for the multivariate regression model. This class of estimators combines high robustness and high efficiency. They are defined by minimizing the determinant of a robust estimator of the scatter matrix of differences of residuals. In the special case of a multivariate location model, the generalized S-estimator has the important independence property, and can be used for high breakdown estimation in independent component analysis. Robustness properties of the estimators are investigated by deriving their breakdown point and the influence function. We also study the efficiency of the estimators, both asymptotically and at finite samples. To obtain inference for the regression parameters, we discuss the fast and robust bootstrap for multivariate generalized S-estimators. The method is illustrated on a real data example.     

Sesquiterpene lactones : A total synthesis of (±)-vernolepin

A novel synthesis of (± )-Vernolepin (1) is described. A suitably substituted cis-fused 2-oxa-3-decalone precursor (29) has been constructed starting from 2,5-cyclohexadiene carboxylic acid via an intramolecular cyclopropanation reaction (23 to 18). The route culminated in the synthesis of Grieco's lactone (53) which has previously been converted to (± )-vernolepin (1) and (± )-vernomenin (2).     

Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient

In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the “added value” we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms. S. Derveaux and B. G. Stubbe contributed equally to this work.     

Intramolecular diels-alder reaction with furan-diene. A novel potential entry to steroids.

Depending on the reaction conditions the intramolecular Diels-Alder reaction of furan-diene $\text{14}$ yields predominantly either one of two adducts $\text{16a}$ and $\text{16b}$, which possess the necessary functionality for eventual transformation into corticosteroids. The dienophile was introduced via alkylation of the enolate, formally obtained upon lithium-liq. ammonia reduction of 3-furyl-2-methyl-2-cyclopentenone ($\text{7}$).     

Intramolecular diels-alder reaction with furan-diene: Total synthesis of (±)-11-ketotestosterone and (±)-adrenosterone

A novel D → BCD → ABCD route to 11 -keto steroids is reported involving a high yield stereoselective intramolecular Diels-Alder reaction of furan-diene $\text{12}$ in water as a key-step. The dienophilic side chain is readily introduced starting from $\text{8}$ via a sequence involving alkylation with ethyl ($\text{E}$)-3-ethoxy-4-iodo-2-butenoate, reduction and acid hydrolysis. The reduced adduct $\text{14}$ is further converted into (±)-adrenosterone ($\text{6}$) via $\text{24}$, the dienediolate equivalent of which is a known intermediate in corticosteroid synthesis.