Fluorinated enol ethers: their synthesis and reactivity.

Thanks to the beneficial effect of fluorine substitution on the pharmacokinetic properties of molecules, an ever increasing number of marketed drugs incorporate a fluorine atom into their structure. As a consequence, the synthesis of fluorinated molecules has become a very active research field. Among the numerous approaches, fluorinated enol ethers are valuable building blocks that allow the introduction of a fluoro- or difluoromethyl group through a wide variety of reactions. The present review lists different methods for their preparation and sums up their numerous synthetic applications.

Understand, elucidate and rationalize the coordination mode of pyrimidylmethylamines: an intertwined study combining NMR and DFT methods.

Conception of new pyrimidylmethylamine (pyrma) ligands and their corresponding Pd(II) complexes has been described. Both symmetrical and non-symmetrical ligands were prepared and subjected to complexation. Two different coordination modes, Pd(N,N)- or Pd(C,N,N)-pyrma, have been evidenced depending on the substitution of the pyrimidine ring and the nature or the shape of the additional pendant arm. In a non-symmetrical pyrimidine series, the substituent-induced discrimination of each heterocyclic nitrogen atom provoked regio-controlled coordination to the metal center. The molecular structure of pyrma-Pd(II) complexes in the solution state has been elucidated thanks to combined NMR experiments and DFT calculations. This study highlights the potency of (15)N and (13)C NMR spectroscopy for the elucidation of the regio-selective coordination to the Pd(II) in the pyrma-based complex series. DFT calculations were highly relevant to the identification of crucial factors that govern the regio-selectivity and the complexation modes. Close predicted and experimental chemical shift values put into relief the reliability of coordination modes for the most stable complexes in solution, depicted by DFT approaches.

Characterization of a monoclonal antibody produced in an attempt to mimic the active site of HIV aspartyl protease using haptens based on inhibitor models.

The high binding affinity and specificity of antibodies for a great variety of ligands has been widely exploited in structure-activity relationship studies of biomolecules and more recently in the development of new catalysts for several chemical reactions. It is assumed that antibodies generated against haptenic protease inhibitors would recognize both these haptens and the substrate of the model proteolytic reaction. We have produced antibodies against HIV PRp12 aspartyl protease substrate analogues, chemically modified at the scissile bond, Phe-Pro. Identical chemical modifications have been reported for related HIV protease inhibitors. We finally selected an anti-hapten monoclonal antibody that specifically recognized the substrate and those haptens with both the phenylalanyl side chain and the prolyl pyrrolidine ring. This selectivity of recognition suggests that such an antibody might mimic the catalytic site of the model protease.

Sulfur-containing 1,3-dialkylxanthine derivatives as selective antagonists at A1-adenosine receptors.

Sulfur-containing analogues of 8-substituted xanthines were prepared in an effort to increase selectivity or potency as antagonists at adenosine receptors. Either cyclopentyl or various aryl substituents were utilized at the 8-position, because of the association of these groups with high potency at A1-adenosine receptors. Sulfur was incorporated on the purine ring at positions 2 and/or 6, in the 8-position substituent in the form of 2- or 3-thienyl groups, or via thienyl groups separated from an 8-aryl substituent through an amide-containing chain. The feasibility of using the thienyl group as a prosthetic group for selective iodination via its Hg2+ derivative was explored. Receptor selectivity was determined in binding assays using membrane homogenates from rat cortex [( 3H]-N6-(phenylisopropyl)adenosine as radioligand] or striatum [3H]-5'-(N-ethylcarbamoyl)adenosine as radioligand] for A1- and A2-adenosine receptors, respectively. Generally, 2-thio-8-cycloalkylxanthines were at least as A1 selective as the corresponding oxygen analogue. 2-Thio-8-aryl derivatives tended to be more potent at A2 receptors than the oxygen analogue. 8-[4-[(Carboxy-methyl)oxyl] phenyl]-1,3-dipropyl-2-thioxanthine ethyl ester was greater than 740-fold A1 selective.

Catalytic asymmetric access to alpha,beta unsaturated delta-lactones through a vinylogous aldol reaction: application to the total synthesis of the Prelog-Djerassi lactone.

[reaction--see text] A one-step catalytic asymmetric access to alpha,beta unsaturated delta-lactones is described, using a vinylogous Mukaiyama-aldol reaction between a gamma-substituted dienolate and various aldehydes in the presence of Carreira catalyst CuF.(S)-tolBinap. This methodology has been further applied to a straightforward access to the Prelog-Djerassi lactone.

Catalytic Asymmetric Vinylogous Mukaiyama-aldol (CAVM) reactions: the enolate activation.

The Catalytic Asymmetric Vinylogous Mukaiyama (CAVM) reactions of various aldehydes with dienolate 1 using different enolate activations (CuF*(S)-TolBinap, t-BuOCu*(S)-Tol-Binap, and various chiral nonracemic ammonium fluorides derived from cinchona alkaloids) are described. These reactions proved to be highly regioselective leading exclusively to the alpha-aldol products in good yields and poor to good enantioselectivities.

Colour vision at very high altitude.

The goal of our study was to evaluate colour vision during high-altitude mountain climbing without supplemental oxygen. Two Himalayan expeditions were invited to test their colour perception at both the highest possible altitude and on the largest possible number of subjects. The panel desaturated D15 was used, because only a simple test could be transported to those altitudes. There were 2 evaluations (i.e., 4 eyes) at 7,000 m during the first expedition in 1997, and 3 evaluations (i.e., 6 eyes) at 6,500 m during the second expedition in 1998. The results were in perfect agreement and can be considered practically normal for all 5 mountain climbers.

5-Benzoyl-5-deacetylwilforidine: a new sesquiterpene nicotinoyl alkaloid from Maytenus buchananii.

A new sesquiterpene nicotinoyl alkaloid has been isolated from Maytenus buchananii (Loes.) R. Wilczek and identified as 5-benzoyl-5-deacetylwilforidine (1). This appears to be the first sesquiterpene nicotinoyl alkaloid based on hydroxywilfordic acid with a benzoyl group at C-5.

New sucrose phenylpropanoid esters from Polygonum perfoliatum.

Five diferuloyl esters of sucrose, 6'-acetyl-3,6-diferuloylsucrose (helonioside B) (1); 2',4',6'-triacetyl-3,6-diferuloylsucrose (2); 1, 2',4',6'-tetraacetyl-3,6-diferuloylsucro se (3); 1,2',6'-triacetyl-3, 6-diferuloylsucrose (4); and 2',6'-diacetyl-3,6-diferuloylsucrose (5), were isolated, along with the 1,3,6-tri-p-coumaroyl-6'-feruloylsucroses, vanicoside A and vanicoside B, from the whole plant of Polygonum perfoliatum by various chromatographic methods. The structures of these phenylpropanoid glycosides were determined on the basis of their NMR and mass spectroscopic data. Compound 1 is a known compound, but 2-5 are new members of this class.