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Aldol addition of α-triisopropylsilyl-α-diazoacetone (TIPS-diazoacetone), promoted by excess lithium diisopropylamide (LDA), was developed and applied to the synthesis of original C-TIPS diazoaldols, C-TIPS diazoketols, and a related Mannich-type product. An unprecedented mechanistic pathway has been proposed, involving a lithiated triazene intermediate resulting from the nucleophilic addition of LDA on the diazo moiety, supported by experimental results and DFT calculations.

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.

International audience; Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics

International audience; An efficient two-step strategy for the synthesis of constrained C-glycosyl amino acid derivatives from C-vinylglycosides involving a 1,3-dipolar cycloaddition using L-(-)menthone-derived nitrone as the key step is described. After optimization of 1,3-dipolar cycloaddition conditions, various C-vinylglycosides were tested leading exclusively to one dia-[a]

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant

Highly diastereo- and enantioselective 1,3-dipolar cycloadditions between functional ketonitrones and β-substituted enals are promoted by organocatalysis with the imidazolidinium catalyst of MacMillan. Study of the scope of the reaction shows that high selectivities are conserved by varying the N-protecting group or the ester function. However it is sensitive to sterical interaction with the C-substituent of the nitrone. Reaction proceeds in all cases with a high exo selectivity. In most cases, a third diastereomer, not compatible with a concerted mechanism, was observed, although in minute amount. DFT calculations evidence that the cycloaddition proceeds in a non-concerted fashion by a first oxa Michael-type addition of the nitrone to the double bond followed by a cyclization. This mechanism explains the formation of the observed minor diastereomers. In addition, the diastereo- and enantioselectivities of the reaction were shown to be intermediately thermodynamically controlled and the diastereomeric ratio is modulated by the kinetics of iminium hydrolysis.

The Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of the steroid synthesis. The products are usually obtained after 3 consecutive steps which are the formation of an enolate (or derivative), a conjugate addition and an aldol reaction. Over the years, several methodological improvements were made for each individual step or alternative routes were devised to access the Robinson annulation products. The first part of this review outlines the most relevant developments towards the formation of Monocarbonyl-derived Robinson Annulation Products (MRA Products, MRAP) and Activated Monocarbonyl-derived Robinson Annulation Products (AMRA Products, AMRAP). The following chapters are then devoted to the diastereoselective and enantioselective access to these products while the last section describes the enantiomeric resolution of racemic mixtures.

The Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of steroid synthesis. The products are usually obtained after three consecutive steps: the formation of an enolate (or derivative), a conjugate addition, and an aldol reaction. Over the years, several methodological improvements have been made for each individual step or alternative routes have been devised to access the Robinson annulation products. The first part of this Review outlines the most relevant developments towards the formation of monocarbonyl-derived Robinson annulation products (MRA products, MRAPs) and activated monocarbonyl-derived Robinson annulation products (AMRA products, AMRAPs). The following sections are then devoted to the diastereoselective and enantioselective synthesis of these products, while the last section describes the enantiomeric resolution of racemic mixtures.

α-Triisopropylsilyl-α-diazoacetone (TIPS-diazoacetone) underwent high-yielding “diazo-side” Mukaiyama aldol-type addition with a range of aryl and alkyl aldehydes when subjected to stoichiometric amount of tetrabutylammonium fluoride at −16 °C, in Et2O. Robustness of the TIPS group makes TIPS-diazoacetone a stable surrogate for α-triethylsilyl-α-diazoacetone, on which generation of the corresponding carbanion can still be efficiently achieved under nucleophilic, weakly basic and practical conditions. These results highlight the synthetic potential that can be expected from TIPS-diazoacetone, promising building block for the convergent elaboration of highly functionalised versatile diazocarbonyl compounds.

International audience; 3,4‐Dihydro‐2H‐pyrans are present in the skeletons of several natural products, and these versatile synthetic intermediates are readily transformed into tetrahydropyrans, pyridines, or 1,5‐dicarbonyl units. Among the strategies developed to access 3,4‐dihydro‐2H‐pyrans, the hetero‐Diels‐Alder reaction between an oxadiene and a dienophile is particularly valuable because up to three contiguous stereogenic centers can be created diastereo‐ and/or enantioselectively in a single step. This review addresses the mechanism of the reaction and presents methods for preparing the product dihydropyrans enantio‐ and diastereoselectively. Thermal and Lewis acid promoted cycloadditions are discussed, as is the role of activating groups on the oxadiene.

There is a dire need for new classes of antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Antibiotic compounds are notorious for not having very “drug-like” chemical structures. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.

International audience; A convergent and rapid synthesis of original C2,C3-unsaturated, C11,C13-keto-enol macrocycles with a peloruside A skeleton has been developed. These original unsaturated macrocycles constitute valuable platforms to access peloruside A analogues with high diversity. The four-fragment strategy implemented features two aldol-type couplings with the central C12-C14 building block TES-diazoacetone and a late-stage ring-closing metathesis. Enantiopure analogue 18ab showed antiproliferative activity in the low micromolar range on NCI and MCF7 tumor cell lines.

The isoxazolidine ring represents one of the privileged structures in medicinal chemistry, and there have been an increasing number of studies on isoxazolidine and isoxazolidine-containing compounds. Optimization of the 1,3-dipolar cycloaddition (1,3-DC), original methods including electrophilic or palladium-mediated cyclization of unsaturated hydroxylamine, has been developed to obtain isoxazolidines. Novel reactions involving the isoxazolidine ring have been highlighted to accomplish total synthesis or to obtain bioactive compounds, one of the most significant examples being probably the thermic ring contraction applied to the total synthesis of (±)-Gelsemoxonine. The unique isoxazolidine scaffold also exhibits an impressive potential as a mimic of nucleosides, carbohydrates, PNA, amino acids, and steroid analogs. This review aims to be a comprehensive and general summary of the different isoxazolidine syntheses, their use as starting building blocks for the preparation of natural compounds, and their main biological activities.

Copper-catalyzed vinylation of 2- and 4-hydroxy pyridine and quinoline affords exclusively N-vinylation products. However, vinyl ethers of 4-hydroxy pyridine and quinoline can be prepared via a three-step sequence involving copper-catalyzed C-O cross coupling reaction of the corresponding N-heteroaryl bromides with ethylene glycol, chlorination of the terminal alcohol, and dehydrohalogenation of the β-chloro ethers. Although not efficient in 2-hydroxy series, this method can be conveniently applied to the preparation of various aza-aryl vinyl ethers in moderate to good overall yields.

The asymmetric access to unreported trans 4-quinolinoxy oxaproline precursors is investigated here in a comparative way by 1,3-dipolar cycloaddition of vinyloxy quinolines with chiral α-alkoxycarbonyl aldonitrones and chiral cyclic surrogates.

International audience; The mixture ZnF2/HFaq./Hamtetraz (Hamtetraz = 5-aminotetrazole) with the molar ratio 10/80/10 reacts at 160 °C in different solvents (methanol/water and water respectively) to give two new 3D compounds: (Zn4F4(amtetraz)4)∙H2O (1) and (Zn4F4(H2O)(amtetraz)4)·H2O (2). The structures, determined by single crystal X-ray diffraction, exhibit neutral 3D-frameworks with narrow cavities that contain water molecules. Each network is built up from two types of parallel chains connected by aminotetrazolate ligands. The comparison of 1 and 2 with literature compounds shows that the nature of the polar solvent, aprotic or protic, influences the network characteristics, as well as the condensation of inorganic species or the bridging mode of the organic moieties. The luminescence properties of the zinc fluoro-aminotetrazolates are discussed.

Aldol-type addition of α-triethylsilyl-α-diazoacetone was achieved under nucleophilic activation by tetrabutylammonium fluoride (TBAF). The use of a semistoichiometric amount of TBAF (protocol P1) provided the corresponding β-hydroxy-α-diazoacetone as the sole product. Alternatively, the use of a catalytic amount of TBAF led to a mixture of β-hydroxy- and β-silyloxy-α-diazoacetone products, which was cleanly desilylated with Et3N·3HF (protocol P2). The weakly basic conditions employed tolerate a wide range of substrates and constitute a high-yielding, convenient complementary procedure to the low-temperature LDA-promoted aldol-type addition of diazoacetone.

Bicyclic isoxazolidines displaying one or two quaternary stereocenter(s) were formed starting from functional cyclic ketonitrones equipped with a phenyl glycinol chiral auxiliary. The products were engaged in stereocontrolled 1,3-dipolar cycloaddition reactions with a range of electron-rich and electron-poor dipolarophiles. A new reductive removal of the phenyl glycinol chiral auxiliary was introduced and was shown to afford chemoselectively a quaternary isoxazolidine derivative (of oxaprolinol-type) without cleaving the N–O isoxazolidine bond. Keeping the aldehyde function masked as a cyclic pseudo-acetal, the liberated oxy-amine function was shown to be available for a pseudo-peptide coupling with various N-protected amino acids. The isoxazolidine ring was opened by a reductive N–O bond cleavage, giving a pseudo-dipeptide that was C-terminated with an aldehyde function.

International audience; A stereospecific Mizoroki-Heck cross-coupling of differently substituted glycals with haloarenes resulting in the exclusive formation of either α- or β-aryl-C-glycosides depending solely on the configuration at C3 was achieved. The reaction was easy to set up because no specific precautions were required concerning moisture or oxygen, and it proceeded by a chirality transfer from C3 to C1. After optimization of cross-coupling conditions, various prepared glycals (7 examples) and arenes (10 examples) were tested, leading stereospecifically to the corresponding aryl-C-glycosides with a carbonyl group at C3, thus opening up new horizons for the total synthesis of glycosylated natural products.

International audience; In this paper, a new access to several chiral 3-aminoglycals as potential precursors for glycosylated natural products is reported from a common starting material, (-)-methyl-L-lactate. The stereodivergent strategy is based on the implementation of a ring-closing metathesis of vinyl ethers as key step of reaction sequences developed.

International audience; The synthesis and the reactivity in Diels–Alder and retro Diels–Alder (DA/rDA) reactions of a series of novel phosphonated furan-functionalized PEO monomethyl ethers were investigated. Dimethylphosphonate-terminated furan-functionalized PEO monomethyl ethers and their phosphonic acid-terminated derivatives have been successfully prepared by using a combination of click copper-catalyzed 1,3-dipolar cycloaddition and Kabachnik–Fields reactions. Influence of both the substitution pattern of the furan ring and the solvent onto the DA/rDA process were investigated. It was found that the 3-substituted furan is the more reactive and that water facilitates both the DA and the rDA reactions, while maintaining the polymeric structure intact. The results demonstrate the potential of such structures for dynamic covalent applications and controlled drug delivery systems such as thermoreversible linkage of biological entities onto metallic nanoparticles.

Enantiopure vinyl ethers of Stericol® underwent diastereoselective thermal 1,3 dipolar cycloadditions with N-benzyl, N-benzhydryl, and N-PMB aspartate ester nitrones. Chemoselective N-debenzylation of the resulting cycloadducts afforded diastereomerically and enantiomerically pure crystalline NH-isoxazolidine, the absolute configuration of which was established by X-ray crystallography. N-Protection and N–O cleavage of this isoxazolidine gave enantioenriched quaternary aspartate derivatives bearing functionalized side chains.

Four new hybrid fluoroferrates synthesized with 1,4-diazabicyclooctane (dabco) are discussed. They were obtained through the use of conventional solvothermal synthesis in Teflon vessels to explore the composition space diagram of the (Fe2+,Fe3+)-dabco-HFaq. chemical system with ethanol or dimethylformamide as solvent. These Class I hybrid fluorides exhibit isolated hydrated and/or fluorinated iron entities associated to mono or diprotonated amines according to the synthesis conditions. Their structures were determined from single crystal diffraction: (dabcoH2)[FeIII2F8(H2O)2] (I), triclinic, space group P, Z = 2, a = 7.1657(2) A, b = 7.6031(2) A, c = 13.1497(3) A, α = 73.631(1)°, β = 76.210(1)°, γ = 84.286(1)°, V = 667.1(1) A3, R = 0.0299; (dabcoH2)2[FeIII2F10]·2H2O (II), orthorhombic, space group Pbca, Z = 4, a = 12.9801(7) A, b = 11.4624(6) A, c = 13.8641(7) A, V = 2062.7(2) A3, R = 0.0425; (dabcoH)4[FeIII2F10]·10H2O (III), triclinic, space group P, Z = 1, a = 8.921(3) A, b = 9.468(4) A, c = 13.452(4) A, α = 76.87(2)°, β = 74.62(2)°, γ = 74.86(2)°, V = 1042.2(6) A3, R = 0.0549; (dabcoH)[(FeII(H2O)6)(FeIIIF6)] (IV), trigonal, space group P31c, Z = 2, a = 9.2866(2) A, c = 10.2401(2) A, V = 764.8(3) A3, R = 0.0252. The paper focuses on structural descriptions, environment of dabco cations or iron species, and hydrogen bonding modes in the light of literature examples.

International audience; An efficient access for the synthesis of pluramycinones is described. Total syntheses of racemic γ-indomycinone and kidamycinone were achieved by means of two Diels-Alder reactions. A first Diels-Alder condensation followed by a Stille cross-coupling is used for the elaboration of the desired substituted dienes which will be involved in the second pericyclic reaction with juglone to construct the tetracyclic core of pluramycinones.

A new strategy for the synthesis of acyl β-C-glycosides is described. The reactivity of glyconitriles toward organometallic reagents such as organomagnesium or organolithium derivatives was studied, affording acyl β-C-glycosides in moderate to good yields. In this study, glycal formation was efficiently prevented by deprotonating the hydroxyl group in position 2 of the glyconitriles during the process.

A new strategy for the synthesis of acyl β-C-glycosides is described. The reactivity of glyconitriles toward organometallic reagents such as organomagnesium or organolithium derivatives was studied, affording acyl β-C-glycosides in moderate to good yields. In this study, glycal formation was efficiently prevented by deprotonating the hydroxyl group in position 2 of the glyconitriles during the process.

Aldol-type addition of α-triethylsilyl-α-diazoacetone was achieved under nucleophilic activation by tetrabutylammonium fluoride (TBAF). The use of a semistoichiometric amount of TBAF (protocol P1) provided the corresponding β-hydroxy-α-diazoacetone as the sole product. Alternatively, the use of a catalytic amount of TBAF led to a mixture of β-hydroxy- and β-silyloxy-α-diazoacetone products, which was cleanly desilylated with Et3N·3HF (protocol P2). The weakly basic conditions employed tolerate a wide range of substrates and constitute a high-yielding, convenient complementary procedure to the low-temperature LDA-promoted aldol-type addition of diazoacetone.

Highly enantio- and exo-selective 1,3-dipolar cycloadditions of alanine-derived ketonitrones to E-crotonaldehyde could be realized in a good yield by the use of a chiral imidazolidinone salt without the addition of water. The origin of the stereoselectivity in the reaction was discussed and the absolute configuration of the cycloadduct determined unambiguously.

We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.

A new family of analogs of steganacin, an important antimitotic compound, was accessed. It takes advantage of a completely stereoselective sequence of two key steps. The central dihydropyrane core is built by a highly diastereoselective and facially controlled hetero-Diels–Alder reaction. It is followed by a nonphenolic biaryl oxidative coupling with a complete atropo-stereoselectivity. It leads to a quick way to form cyclic biaryl lignans.

The ketal- or dithioketal-protected isocoumarins 15–18 gave the corresponding 1-naphthols 21–26 in their reactions with the acetoacetate (10) or pentane-2,4-dione (19) dianions and the acetone monoanion. Subjection of the dithioketal-protected ester 28 to Baker–Venkataraman reaction conditions led to the 8-deoxy tautomeric, protected forms 29/30 of the early decaketide antibiotic intermediate 2b. However, the dithioketal protecting groups could not be removed without destruction of the molecule. Consequently the silyl-protected unstable early tri- and tetracyclic decaketide biosynthesis intermediates 37a, 37b, and 38a (precursors of angucycline and anthracycline antitumor antibiotics) were prepared through silylation of 33a and 33b, to afford 34a and 34b, and subsequent treatment with acetylacetone dianion. The ultimate synthetic goal, the silyl-protected 2,3-dialkylated naphthol derivative 41, was achieved by selective elongation of the bottom chain of the bis-silyl-protected methyl ester 36 with acetylacetone dianion.

The first de novo synthesis of a beta-C-naphthyl glycoside displaying a convenient functionality for subsequent transformations into complex C-aryl glycosides is reported. The synthesis of this (+/-)-beta-C-1,5-dibenzyloxynaphthyl 6,6,6-trifluoro-3-amino glycoside relies on a hyperbaric HDA reaction involving a new 2-vinylnaphthalenic dienophile.

International audience; C-Naphthyl glycosides displaying a 1,5-difunctionality on the naphthalene ring that can undergo oxidation to bromonaphthoquinone are key intermediates in the synthesis of natural C-aryl glycoside analogues. In this area, sugar-modified derivatives are of specific interest, but their synthesis is challenging. The de novo access to such compounds has been investigated through a [4+2] heterocycloaddition route, previously validated in a model series. For this purpose, two new dienophiles, conveniently protected at the phenolic positions, were synthesized. From an extensive study of their reactivity towards a range of 4-hetero-substituted (''prosugar'') heterodienes, the expected heteroadducts were stereoselectively obtained in acceptable yields. Application of the hydroboration/reduction/oxidation sequence did not afford the target C-glycosides from the reduced adducts. The negative effect of the conformational bias of the substrate on this tandem reaction is discussed. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A new practical approach to enantioenriched carboxy-differentiated aspartate derivatives was achieved in three steps via the 1,3-dipolar cycloaddition of N-benzyl-α-carbonyloxyethylnitrone with (R)-4-ethyl-N-vinyloxazolidin-2-one and chemoselective nucleophilic displacement of aspartimide under appropriate conditions (racemization less than 3%).

A new approach to enantiopure disubstituted oxaprolinol derivatives through diastereoselective [3+2]-cycloaddition of chiral cyclic ketonitrones to electron-rich and electron-poor dipolarophiles is presented.

The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports.

The exploration of the FeF3/FeF2-Hamtetraz-HF system in dimethylformamide by solvothermal synthesis evidences two isostructural 3D hybrid fluoroferrates. They are prepared from the same starting mixture at two different synthesis temperatures: 120 °C for [Hdma]·(Fe4IIFeIIIF8(H2O)2(amtetraz)4) (1) and 140 °C for [Hdma]1.5·(Fe4.5IIFe0.5IIIF7(H2O)(HCOO)(amtetraz)4) (2). Both compounds are characterized by single crystal X-ray diffraction, X-ray thermodiffraction, TGA analysis, Mössbauer spectrometry and SQUID magnetometry. They crystallize in the monoclinic system and are built from two distinct chains connected by aminotetrazolate anions. The first chain ∞(FeIIFN4) is common to 1 and 2 and can be found in numerous fluorides. In the second chain ∞(Fe3X12) (X = F, N, O), iron cations adopt both valence states Fe(II)/Fe(III). The hydrolysis of DMF implies the formation of a [Hdma]+ cation and a (HCOO)− anion. The presence of Fe3+ in both phases is evidenced by 57Fe Mössbauer spectrometry. The magnetic properties are studied and two transitions from a paramagnetic regime to a long range ordered state below 30 K and 5 K are identified. Postprint

Asymmetric access to novel N-protected (di)peptidyl β3-aldehydes (“β3-PAs”) has been achieved through direct coupling of a chiral non-racemic 6-alkoxytetrahydrooxazinone with N-phthalyl L-α-amino acids. Kinetic resolution allows for the fruitful use of racemic amino acids in this process. Acidic hydrolysis of the diastereomerically pure, coupling products leads to the title N-phthalyl-β3-PAs in high yields. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Based on a heterocyclic Diels–Alder strategy, a concise synthesis of 5-aza-analogues of angucyclines bearing a 2-deoxy-C-glycoside subunit is reported. Starting from a common intermediate, a peracetylated D-2-deoxyglucose could be linked to carbons C9 or C10 of the tetracyclic framework. Further manipulations of the sugar residue allowed the installation of bromo and azido substituents at carbon C6′.

[reaction: see text] Under standard hydroboration-oxidation conditions, the dihydropyrans 4 underwent a highly stereocontrolled tandem reaction, involving the expected hydration of the double bond together with the reduction of the ketal moiety. This unprecedented transformation gives rise to a short, [4 + 2]-based synthetic route to (+/-)-beta-C-naphthyl-2-deoxyglycosides 5, which allows a significant structural and functional diversity at C-6. We thus described the first synthesis of (+/-)-C-aryl-6-fluoro and -6,6-difluoro olivosides, via the allylic mono- and difluorides produced by regioselective fluorination of, respectively, hydroxyalkyl and oxoalkyl dihydropyran derivatives.

A new route to synthetize the pentaerythrityl tetramine (tetra), C(CH2NH2)4, is established with a good overall yield (75–80%) and four hybrid fluorides, templated by tetra, are synthetized by hydrothermal technique and microwave heating: cis-[H4tetra]•(AlF5)2 (I), trans-[H4tetra]•(AlF5)2 (II), [H4tetra]•(AlF6)•(Cl) (III) and (H3O)•[H4tetra]2•(Ga(OH)2F4)•(GaF6)2•2H2O (IV). Structural determinations are performed from single crystal X-ray diffraction data. Structures of I and II are built up from infinite ( AlF 5 ) 2 − ∞ chains of corner sharing AlF6 octahedra; the octahedra are cis-connected in I and trans-connected in II. III and IV are molecular phases and consist of isolated AlF6 (III) or Ga(OH)2F4 and GaF6 (IV) octahedra. Isolated chloride ions are found in III. Charge balance is ensured by tetraprotonated amine [ H 4 tetra ] 4 + and the cohesion between inorganic and organic parts is due to hydrogen bonds.

Tren amine cations and carbonate anions adopt a ternary symmetry while tetra amine cations are tetrahedral. The symmetry of these constitutive ions influences strongly the nature of the solids which crystallise from solutions. Large fluorinated aluminate polyanions with tetrahedral symmetry appear in the presence of tren amine, while infinite chains of AlF6 octahedra are observed with tetra amine and that noncentrosymmetric structures are frequently encountered in rare earth fluoride carbonates.

Stereoselective ethynylation of functionalized β-C-glycosyl aldehydes has been achieved with various organometallic alkynes. The diastereoselectivity is highly dependent on the organometallic alkyne and on the functionalization on the C-6 position of the glycoside. The stereoselective reaction conducted with ester-functionalized aldehyde, followed by Mitsunobu reaction and two Pd-catalyzed regio- stereo- and enantioselective alkylations afforded the “western” part of ambruticin. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

For the first time, easily available N-(alpha-methoxyalkyl)amides were successfully used as synthetic equivalents of N-acylimines in an asymmetric heterocycloaddition process. The facial-controlled formation of 6-alkoxydihydrooxazines was thus achieved by SnCl(4)-promoted heterocycloaddition of (R)-O-vinyl pantolactone. By simple acidic hydrolysis of the crude heteroadducts, new beta-aryl- and beta-alkyl-substituted benzamido aldehydes were thus obtained in good overall yields with high enantioselectivities.

The synthesis of chiral 1,2,3,5-substituted tetrahydropyrans has been realized via an asymmetric hetero Diels–Alder (HDA) reaction. The key step that involved a trisubstituted chiral enol ether derived from (R)-mandelic acid as the dienophile promoted the creation of three stereogenic centers with a remarkable and unprecedented endo and facial stereocontrol. The hydrogenation of the heteroadduct 2 was optimized by using Pd on charcoal and diisopropylethylamine, leading to a unique isomer. The chiral inductor was cleanly and stereoselectively removed via an acetal reduction, which demonstrated the potential of this methodology for the efficient construction of key intermediate of biologically active molecules.

A high yielding, general, and practical procedure for the N-vinylation of 2-oxazolidinones via TMSOTf-promoted dehydroalkoxvlation of N,O-acetals is described.

The first example of a high facial selective [3 + 2] cycloaddition employing chiral vinyl ethers as dipolarophile and nitrones as dipoles is presented.

International audience; The exploration of the composition space diagram of the FeF3/ZnF2–Hamtetraz-HFaq system (Hamtetraz = 5-aminotetrazole) by solvothermal synthesis at 160 °C for 72 h in dimethylformamide (DMF) has evidenced five new hybrid fluorides (1–5); the structures are characterized from single crystal X-ray diffraction data. [Hdma]·(ZnFeIII(H2O)4F6) (1) and [Hdma]·[Hgua]2·(FeIIIF6) (2) contain anionic inorganic chains (1) or isolated octahedra (2) weakly hydrogen bonded (Class I hybrids) to dimethylammonium (Hdma) and/or guanidinium (Hgua) cations which are produced from the tetrazole ligand and solvent decomposition. [Hdma]2·[Hgua]·[NH4]·[ZnFeIIIF5(amtetraz)2]2 (3), [Hdma]2·[Zn1.6FeII0.4FeIIIF6(amtetraz)3] (4), and [Hdma]·[Zn4F5(amtetraz)4] (5) are considered as Class II hybrids in which the (amtetraz)− anions are strongly linked to divalent metal cations via N–M bonds. In 3, ∞{[NH4]·[ZnFeIIIF5(amtetraz)2]2} layers are separated by [Hdma]+ and [Hgua]+ cations. 4 and 5 exhibit three-dimensional (3D) hybrid networks that contain small cavities where [Hdma]+ cations are inserted. A porous 3D metal–organic framework intermediate is evidenced from the thermogravimetric analysis and X-ray thermodiffraction of 5.