Highly enantioselective darzens reaction of a camphor-derived sulfonium amide to give glycidic amides and their applications in synthesis

The reaction of an amide-stabilized sulfonium ylide bearing chiral groups on sulfur has been investigated. We have discovered that the camphor-derived amide-stabilized ylide reacts with aldehydes at -50 degrees C in ethanol to give glycidic amides in one step with up to 99% ee and complete diastereoselectivity. From analyzing reactions of different ratios of diastereomers at sulfur it was found that the major diastereomer gave very high enantioselectivity, while the minor one gave much lower selectivity (54% ee). Further mechanistic studies have revealed that enantioselectivity is controlled not in the betaine-forming step (C-C bond formation is reversible) but in the different barriers to bond rotation around the newly formed C-C of the two diastereomeric betaines. Further transformations of epoxyamides were investigated. It was found that epoxyamides could be converted into epoxyketones by reaction with organolithium reagents and that they could be ring-opened by nucleophiles with complete regioselectivity using Yb(OTf)3. The practicality of the process has been exemplified in the synthesis of SK&F 104353, a leukotriene D4 antagonist in the potential treatment of bronchial asthma.     

Detection of reactive free radicals derived from nucleosides by liquid chromatography coupled to tandem mass spectrometry of DMPO spin trapping adducts

In this study, reactive free radicals derived from several nucleosides were spin trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and then detected by high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). This method provides a specific detection of spin trapping adducts derived from nucleosides with a very high sensitivity: quantities as low as 0.5 picomoles of spin trapping adducts corresponding to concentrations of 2.5 10(-8) mol . L(-1) were detected. Different spin trapping adducts were characterized by HPLC/ESI-MS/MS in three well-known systems producing free radicals photochemically: the photolysis of 5-halo-2'-deoxyuridines, the photolysis of 5-thiophenylmethyl-2'-deoxyuridine and the photolysis of thymidine with menadione bisulfite as a photosensitizer. A new radical photoreactivity of uridine derivatives was also detected by this method both at the nucleoside and at the RNA level, showing that the method is also relevant for studying spin trapping adducts derived from DNA and RNA strands.     

N-acylation of 1,3-dimethyl-6-aminouracils. A reversal in the regiospecificity of an electrophilic substitution induced by an intramolecular proton-transfer

Electrophilic reactions of 1,3-dimethyl-6-aminouracil lead to 5-substituted derivatives. The introduction of a dialkylaminoalkylamino chain in the 6-position of 1,3-dimethyluracil modifies the regiospecificity of the acylation reaction to give N-6 acylated compounds. This reversal in acylation is induced by an intramolecular proton-transfer which introduces a change in the electron density of the enamine system. The cyclic transition state and the spatial conformation of the final products substantiate the proposed mechanism, on the basis of X-ray and ¹H nmr data.     

Construction of spirolactones with concomitant formation of the fused quaternary centre--application to the synthesis of natural products

Polycyclic structures fused at a central carbon are of great interest due to their appealing conformational features and their structural implications in biological systems. Although progress in the development of synthetic methodologies towards such structures has been impressive, the stereoselective construction of such quaternary stereocentres remains a significant challenge in the total synthesis of natural products. This review highlights the progress in the formation of 1-oxaspiro[4.n]alkan-2-ones (2≤n≤7) with concomitant formation of the quaternary spiro centre.     

Dienophilie des cyano-1 enamines,nouveaux equivalents de cetenes pour les cycloadditions de diels-alder1

The Diels-Alder reactivity of two captodative olefins, 2-morpho-lino-acrylonitrile $\text{15}$ and 2-(N-methlanilino) -acrylonitrile $\text{16}$, towards four conjugated dienes is evaluated.In every cases, isomeric {4+2} cyclo-adducts are obtained.With olefin $\text{15}$ yields are better than with olefin $\text{16}$. The adducts are easily transformed in to the corresponding ketones by a mild hydrolysis of the α-aminonitrile group. Thus, the 1-cyanoenamines can be considered as good ketene equivalents very useful for the synthesis of unsaturated cyclohexanones.     

Synthesis of β-pyrazinyl-L-alanine (Paa) and of peptide derivatives

The title compound was prepared via a malonic ester synthesis starting with α-chloromethylpyrazine [2], and ending, after an asymmetric enzymatic hydrolysis of the racemic N-acetyl-β-2-pyrazinylalanine to the L -form of the new amino acid. The optical purity was ascertained by ¹H-NMR analysis at 360 MHz of the diastereoisomeric dipeptides L -pyrazinylalanine-L -leucine and D -pyrazinylalanine-L -leucine. Hydrophobic, steric and electronic parameters for its side chain were also estimated, which can be useful for the quantitative study of structure-activity relationships of biologically active peptide derivatives. The new amino acid could be introduced in the place of phenylalanine in the enkephalin-like pentapeptide [D -alanyl², leucine⁵]enkephalin, thus showing good stability towards the classical methods of peptide synthesis.     

Asymmetric Palladium-Assisted Alkylation of Alkenes

Palladium-promoted alkylation of alkenes using chiral sulfoxide-containing carbanions and chiral lithiated oxazolines results in asymmetric induction (AI) ranging from 3–5% (1,5 induction), 20–40% (1,3 induction) to 44–52% (1,4 induction). No general trend allowing predictions of results was found. With 1-hexene, attack at C(1) is almost exclusive but propene gives a mixture of attack at C(1) and C(2). The use of a chiral ligand together with malonate anion also leads to some asymmetric induction (ca. 20%).     

On the representation of integers as linear combinations of consecutive values of a polynomial

Let be a cyclotomic field with ring of integers and let be a polynomial whose values on belong to . If the ideal of generated by the values of on is itself, then every algebraic integer of may be written in the following form:

for some integer , where the 's are roots of unity of . Moreover, there are two effective constants and such that the least integer (for a fixed ) is less than , where

     

On signature-based expressions of system reliability

The concept of signature was introduced by Samaniego for systems whose components have i.i.d. lifetimes. This concept proved to be useful in the analysis of theoretical behaviors of systems. In particular, it provides an interesting signature-based representation of the system reliability in terms of reliabilities of k-out-of-n systems. In the non-i.i.d. case, we show that, at any time, this representation still holds true for every coherent system if and only if the component states are exchangeable. We also discuss conditions for obtaining an alternative representation of the system reliability in which the signature is replaced by its non-i.i.d. extension. Finally, we discuss conditions for the system reliability to have both representations.