Synthesis and biological activities of substituted dihydrobenzo[h]-pyrimido[4,5-b]quinolines as tetracyclic 5-deaza nonclassical folates

Novel tetracyclic compounds 1–4 have been synthesized via a regiospecific cyclocondensation reaction between substituted 6-aminopyrimidines 5– 7 and chlorovinyl aldehydes 13 and 14 . The linear structures of these compounds were established by ¹H nmr and ¹³C nmr spectral data and also by synthesis of the compounds via an unambiguous route. The growth of Manca human lymphoma cells was inhibited 50% by 1 and 4 at 4.5 × 10^?6 M and 1.2 × 10^?6 M respectively. These compounds also inhibited human dihydrofolate reductase (DHFR)by 50% at 4.4 × 10^?6 M and 1.4 × 10^?6 irrespectively and L. casei DHFR at 1.9 × 10^?5 M and 1.1 × 10^?5 M respectively. Compound 16 , a positional isomer of 1 , was the most potent of the compounds studied, it inhibited the growth of Manca human lymphoma cells by 50% at 9 × 10^?8 M. The IC₅₀ values of 16 for the inhibition of human DHFR and L. casei DHFR were 8 × 10^?8 M and 1.9 × 10^?5 M respectively.     

Palladium catalysed enantioselective phosphination reactions using secondary phosphine-boranes and aryl iodide

Preliminary results dealing with the enantioselective version of the C-P cross-coupling reaction between dissymmetric secondary phosphine-borane complexes and aryl iodide derivatives are presented. To gain information on the enantiodiscriminating step, direct observation of an intermediate involved in the catalytic cycle has been achieved by (31)P NMR spectroscopy.     

Thiazolinium salt: an efficient catalyst for the Mukaiyama reaction

Mukaiyama aldol reaction between benzaldehyde and Danishefsky diene is promoted by ionic liquid-type salts. Hence, thiazolinium salts have been found to be the most efficient for this transformation. On a mechanistic point of view, only the Mukaiyama process is observed without any hetero Diels-Alder cycloaddition. In some cases, cyclisation of the Mukaiyama adduct occurred without addition of TFA. Interestingly, the thiazolinium catalyst can be recycled at least 10 times without loss of activity.     

Singularities of the solution of a mixed problem for a general second order elliptic equation and boundary stabilizationof the wave equation

We deal here with a second order elliptic mixed problem which is posed in a regular open bounded domain of . We study the regularity of its solution. We apply our results to the boundary stabilization of the wave equation.     

Pyridinedithioesters as heterodienophiles: application to the synthesis of aprikalim

[reaction: see text] Pyridinedithioesters can be used as efficient heterodienophiles when activated by complexation with BF(3), by protonation, or by oxidation of the nitrogen atom of the pyridine moiety. The hetero-Diels-Alder reaction using 3-pyridinedithioester as a heterodienophile was the key step in a new synthesis of Aprikalim in racemic form. The methodology can be reliably extended to prepare new analogues of Aprikalim.     

Catalytic materials based on catalysts containing ionic liquid phase supported on chitosan or alginate: Importance of the support

Catalysts containing an ionic liquid phase immobilised on chitosan or alginate supports are successfully applied to the palladium catalysed allylation and amination reactions. The influence of the chemical structure of the support not only on the activity, but also on the recyclability and the reusability of the catalyst, is evaluated.     

Copper-catalyzed synthesis of alkynylphosphine derivatives: unprecedented use of nucleophilic phosphorus compounds

A new and smooth approach towards alkynylphosphine derivatives is described. It relies on the unprecedented catalytic coupling of secondary phosphine boranes with alkynyl bromides using the CuI/1,10-phenanthroline couple.     

Ph2P(BH3)Li: from ditopicity to dual reactivity

A multinuclear NMR study shows that the deprotonation of diphenylphosphine-borane by n-BuLi in THF leads to a disolvated lithium phosphido-borane Ph(2)P(BH(3))Li of which Li(+) is connected to the hydrides on the boron and two THF molecules rather than to the phosphorus. This entity behaves as both a phosphination and a reducing agent, depending on the kinetic or thermodynamic control imposed to the reaction medium. Density functional theory computations show that H(2)P(BH(3))Li exhibits a ditopic character (the lithium cation can be in the vicinity of the hydride or of the phosphorus). It explains its dual reactivity (H- or P-addition), both routes going through somewhat similar six-membered transition states with low activation barriers.     

Synthesis and properties of thiazoline based ionic liquids derived from the chiral pool

A novel class of chiral ionic liquids derived from amino alcohols is prepared in multi-gram scale. Their potential in chiral recognition is shown in a preliminary example with racemic Mosher's acid salt.