Exaltone® (=Cyclopentadecanone) from Isomuscone® (=Cyclohexadecanone), a One‐C‐Atom Ring‐Contraction Methodology via a Stereospecific Favorskii Rearrangement: Regioselective Application to (−)‐(R)‐Muscone

Treatment of cyclohexadecanone ( 1g ; with I₂ (2.2 mol‐euqiv.) and KOH in MeOH) furnished the unsaturated (Z)‐ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3‐chloroperbenzoic acid (m‐CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone^® (=cyclopentadecanone; 1f ) with NaOH in MeOH/H₂O and then HCl at 65°. This methodology was similarly extended to higher (C₁₇) and lower (C₁₅ to C₁₁) cyclic ketone analogues, as well as regioselectively to (?)‐(R)‐muscone ( 5c ) and homomuscone ( 5f ) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1‐oxaspiro[2,n]alkanes and ‐alkenes 4 and 8 , resulting from a Corey? Chaykovsky oxiranylation, are also presented.     

Synthesis of New N‐(5‐Oxo‐2,5‐dihydro)pyrrol‐3‐yl Glycines and N‐(5‐Oxo‐2,5‐dihydro)pyrrol‐3‐yl Glycines Esters

Following our efforts towards the synthesis of new potential inhibitors of Xanthine Dehydrogenase (XDH), we describe here a general method for the preparation of N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycines and N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycine esters from glycine ethyl ester hydrochloride and various 4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid esters and carbonitriles.     

New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design,Synthesis and Biological Evaluation

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.     

Unraveling the Crystal Structure of Lanthanide–Murexide Complexes: Use of an Ancient Complexometry Indicator as a Near‐Infrared‐Emitting Single‐Ion Magnet

Herein, we provide some structural evidence of the complexation color‐change of murexide solutions in presence of lanthanide, which has been used for decades in complexometric studies. For Ln=Sm to Lu and Y, the compounds crystallize as monomeric [Ln(Murex)₃] ? 11 H₂O with an N3O6 tricapped square‐antiprism environment, which are stable up to 250 °C. Single‐ion magnet (SIM) behavior is then observed on the Yb^III derivative in an original nine‐coordinated environment. In‐field slow relaxation (Δ=(15.6±1) K; τ₀=2.73×10^?6 s) is observed with a very narrow distribution of the relaxation time (α_max=0.09). Magnetic and photophysical properties can be correlated. On one hand the analysis of NIR emission spectrum permits to have access to crystal field parameters and to compare them with those extracted from dc measurements. On the other hand, magnetic measurements permit to identify the nature of the M _J states involved in the ²F_5/2→²F_7/2 luminescence spectrum. The gap between the low‐lying states is in agreement with the energy barrier obtained from magnetic slow‐relaxation measurement.     

Click approaches in sol–gel chemistry

The combination of the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction with sol–gel processing enables the versatile preparation of sol–gel materials under different shapes with targeted functionalities through a diversity-oriented approach. In this account, the development of the CuAAC reaction under anhydrous conditions for the synthesis of sol–gel precursors and for the assembling of magnetic nanoparticles on self-assembled monolayers is related, as well as the use of the classical CuAAC methodologies for the functionalization of mesoporous silica nanoparticles and microdots arrays. Coupling CuAAC and Sol–Gel will result in simplified preparations of multifunctional materials with controlled morphologies.     

Stationary Analysis of a Fluid Queue Driven by Some Countable State Space Markov Chain

Motivated by queueing systems playing a key role in the performance evaluation of telecommunication networks, we analyze in this paper the stationary behavior of a fluid queue, when the instantaneous input rate is driven by a continuous-time Markov chain with finite or infinite state space. In the case of an infinite state space and for particular classes of Markov chains with a countable state space, such as quasi birth and death processes or Markov chains of the G/M/1 type, we develop an algorithm to compute the stationary probability distribution function of the buffer level in the fluid queue. This algorithm relies on simple recurrence relations satisfied by key characteristics of an auxiliary queueing system with normalized input rates.      

On pathwise behavior of multiserver queues

In this paper, by exploiting recent results on the pathwise behavior of the workload process in single server, work conserving queues of theG/G/1/ type, we show that the workload of multiserver, work conserving queues ofG/G/m/ (m<) (andG/G/) queues satisfies an o(t) growth condition, provided that the time average of the work brought into the system is less thanm form < (and finite form=).