‘O-Acyl isopeptide method’ for the efficient synthesis of difficult sequence-containing peptides: use of ‘O-acyl isodipeptide unit’

A novel ‘O-acyl isodipeptide unit’, Boc-Thr(Fmoc-Val)-OH 5 has been successfully used for the efficient synthesis of a difficult sequence-containing pentapeptide based on the ‘O-acyl isopeptide method’, in which racemization-inducible esterification could be omitted, suggesting that the use of O-acyl isodipeptide units allows the application of this method to fully automated protocols for the synthesis of long peptides or proteins.     

‘Locking’ dendrimer conformation through metal coordination

Chiral intramolecularly hydrogen-bonded dendrons that fold into a dynamically biased helical conformation can be ‘locked’ in kinetically controlled conformations by coordination to copper(II) metal centers. Covalent bonding of each pyridine-2,6-dicarboxamide repeat unit of the dendrons to a copper metal center forces this subunit to exist in only the syn-syn conformation and dramatically rigidifies the dendron structure.     

Synthesis of a series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides

A series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides 1a-d, analogues of 3TC that has high biological activities against HIV and HBV, have been synthesized from the gem-difluorohomoallyl amine 7 in a straightforward fashion. Our synthesis featured the construction of thiofuranose skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group in compounds 13a,b.     

Addition d’aminoalcools hautement fluorés sur les isocyanates d’alcoxy et d’aroxysulfonyle

The action of F-alkylated (alkylamino)ethanols on alkoxy- and aroxy-sulfonyl isocyanates allowed the preparation of the corresponding carbamates. The reaction occurred rapidly with good yields.     

Regioselective synthesis of functionalized naphtho[b]thiophenes through a ‘lactone methodology’

Benzo[b]thiophene and its benzannulated derivatives are important classes of compounds due to their unique chemical properties and biosteric relationship with indole. In this letter, we report a convenient route for the synthesis of substituted naphtho[b]thiophenes through a ring transformation reaction of suitably functionalized 2H-pyran-2-ones with 6,7-dihydro-5H-benzothiophene-4-one, in good yields.     

Synthèse en une étape de N-méthoxyindolinones, de N-méthoxymaléimides et d’anhydrides maléiques à partir d’acides hydroxamiques α-halogénés

α-Halo hydroxamic acids were used in the synthesis of N-methoxyindolinones, symmetric and dissymmetric N-methoxymaleimides in good yields. The hydrolysis of N-methoxymaleimides constitues a new and good route to maleic anhydrides.     

Synthesis of ‘three-petal’ carbocyclic systems based on s-cis-diferrocenyltrienes

Acid-catalyzed intramolecular, homoannular alkylation of one of the ferrocenyl substituents in spirocyclodimers derived from 1,3-bis(ferrocenylmethylidene)-2-methylidene-cyclohexane, -cycloheptane, and 3,5-bis(ferrocenylmethylidene)-4-methylidene-N-methylpiperidine results in a fused system with a ‘three-petal’ moiety in the center. The structure of 1-ferrocenyl-3,11-bis(ferrocenylmethylidene)-2,3,4,5,6,6b,10,10a,11,12,13,14-dodecahydro-1H-benzo[d](ferroceno[a])phenanthrene was established by X-ray diffraction analysis.     

Enantioselective synthesis of homocarbocyclic-2′-oxo-3′-azanucleosides

The enantioselective synthesis of homocarbocyclic-2′oxo-3′-azanucleosides has been performed by cycloaddition reaction of the N-glycosyl nitrones with allyl nucleobases. The use of nitrones originated from two different carbohydrates, the N-ribosyl nitrone and the N-mannosyl nitrone, proceeded in a stereocontrolled and predictable manner with a good degree of enantioselectivity, so allowing an easy entry to both enantiomers.     

N,N′-Diisopropyl- and N,N′-dicyclohexylthiourea cadmium(II) complexes as precursors for the synthesis of CdS nanoparticles

Crystals of the cadmium(II) complexes of N,N-diisopropylthiourea and N,N-dicyclohexylthiourea were obtained and their X-ray single crystal structures determined. These complexes are air-stable, easy to prepare and inexpensive and decompose cleanly to give good quality crystalline CdS. The nanoparticles of CdS thus obtained showed quantum confinement effects in their optical spectra, with close to band-edge emission in luminescence experiments. The broad diffraction patterns observed are typical of nanodimensional particles. The variation of concentration of precursor-to-HDA ratio change the isolated materials from spheres to rod-shaped. TEM images showed agglomerates of needle-like plate of particles.     

Efficient production of raspberry ketone via ‘green’ biocatalytic oxidation

For the development of a ‘green’ oxidation method, the transformation of 4-(p-hydroxyphenyl)butan-2-ol (rhododendrol) into 4-(p-hydroxyphenyl)butan-2-one (raspberry ketone) was used as a model reaction. Different lyophilized cells of Rhodococcus spp. have been screened for their ability to perform the desired oxidation. Rhodococcus equi IFO 3730 and R. ruber DSM 44541 were able to use acetone as a hydrogen acceptor in a hydrogen transfer-like process. The oxidation can be performed at substrate concentrations up to 500 g/L.     

Densities and isothermal compressibilities of ionic liquids—Modeling and application

Two corresponding-states forms have been developed for direct correlation function integrals in liquids to represent pressure effects on the volume of ionic liquids over wide ranges of temperature and pressure. The correlations can be analytically integrated from a chosen reference density to provide a full equation of state for ionic liquids over reduced densities from 1.5 to more than 3.6. One approach is empirical with 3 parameters, the other is a 2-parameter theoretical form which is directly connected to a method for predicting gas solubilities in ionic liquids. Parameters for both methods have been obtained for 28 different ionic liquid systems by reduction of carefully validated PρT data. The results show excellent agreement with the experimental data for nearly all substances over all ranges of conditions. Group contributions to parameters are also explored, leading to an entirely predictive method for ambient pressure densities and densities of compressed ionic liquids. Extensive comparisons are made with other techniques.     

P′CP′-Pincer palladium complex-catalyzed allylation of N,N-dimethylsulfamoyl-protected aldimines

The P′CP′-pincer palladium complex-catalyzed allylation of N,N-dimethylsulfamoyl-protected aldimines with allyl(tributyl)stannane is investigated for the preparation of N-homoallylic sulfamides. The desired N,N-dimethylsulfamoyl-protected products are obtained in moderate to high yields in DMF under very mild conditions and a high yielding and convenient deprotection of the N,N-dimethylsulfamoyl group is also demonstrated.     

Synthesis of substituted thiazolo[4,5-b]pyridines and other annulated heterocycles via SN2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions

A new combinatorial method for the preparation of substituted thiazolo[4,5-b]pyridines, which utilizes cyanoacetamide, heterocumulenes (isothiocyanates, carbon bisulfide), and ethyl-4-chloroacetoacetate in a new S_N2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions has been developed. The obtained thiazolo[4,5-b]pyridines were then used together with aldehydes and malononitrile in another Knoevenagel reaction→Michael reaction→hetero-Thorpe-Ziegler domino reaction for the synthesis of substituted 4,6-dihydro-5H-pyrano[2,3-d]thiazolo[4,5-b]pyridines.     

Condensations of N-arylhydroxylamines for the preparation of 5,5′-di-tert-butyl-2,2′-dihydroxydiphenylamine

Acid-promoted condensation of 4-tert-butyl-2-hydroxylaminoanisole with p-tert-butylphenol resulted in the formation of 5,5′-di-tert-butyl-2,2′-dihydroxydiphenylamine upon demethylation with BBr₃. Protection of the acidic phenol unit was required to isolate the acid labile N-arylhydroxylamine intermediate.     

Stereoselective synthesis of (−)-microcarpalide

A highly convergent and efficient synthesis of (−)-microcarpalide, a 10-membered lactone displaying remarkable microfilament disrupting activity is described. Ring-closing metathesis and Sharpless asymmetric dihydroxylations are the key steps. Our strategy highlights the application of novel hydroxy lactone precursors for the stereoselective synthesis of (−)-microcarpalide.     

Tailoring “non conventional” ionic metallomesogens around an ortho-palladated fragment

A series of new ionic ortho-palladated mesogenic complexes [Pd(L)(4,4′-Rⁿ-bpy)][X] of unusual molecular shape have been prepared and characterised. The effect of slight structural changes on the molecular organization in the liquid crystalline phase is discussed in relation with their potential application as molecular materials.     

2′-Lipid-modified oligonucleotides via a ‘Staudinger-Vilarrasa’ reaction

We report a new access to 2′-amido-2′-deoxyuridine via a Staudinger-Vilarrasa coupling reaction for the preparation of lipid-modified oligonucleotides. One or two lipidic moieties were inserted within the oligonucleotidic sequence (LONs) leading to a repertoire of original antagomir-like molecules targeting micro RNA (miRNA or miR). Melting temperature (Tm) experiments revealed that the stability of the duplexes depends on the lipid position and the number of lipid moieties inserted within the oligonucleotide sequence. Single lipid conjugations of positions 11 and 19 of LONs targeting miR-122 do not destabilize the duplexes.     

Bioreduction of methyl o-chlorobenzoylformate at 500 g L without external cofactors for efficient production of enantiopure clopidogrel intermediate

Biocatalytic reduction of methyl o-chlorobenzoylformate (CBFM) provides a green and direct access to methyl (R)-o-chloromandelate [(R)-CMM], an intermediate for a platelet aggregation inhibitor named clopidogrel. As much as 500 g L⁻¹ of CBFM was stoichiometrically converted into enantiopure (R)-CMM at 20 °C by using a whole-cell catalyst coexpressing an aldo-keto reductase from Bacillus sp. and a glucose dehydrogenase (GDH). In addition to the high productivity of 812 g L⁻¹ d⁻¹, this new whole-cell reduction is attractive by eliminating the need of an added external cofactor.     

A new route to 2,2′,3,3′-tetrasubstituted binaphthyls

Based on an ortho-lithiation protocol of 2,2′-dibromo-1,1′-binaphthyl four tetrasubstituted binaphthyls, 2,2′-dibromo-3,3′-diiodo-, 3,3′-dibromo-2,2′-diiodo-, 2,2′,3,3′-tetrabromo-, and 2,2′,3,3′-tetraiodo-1,1′-binaphthyls have been prepared in excellent yield which in turn proved to be versatile key intermediates in the synthesis of various 2,2′,3,3′-tetrasubstituted 1,1′-binaphthyl derivatives.     

Acid-catalyzed condensation of 2,2′-diamino-1,1′-biaryls for the synthesis of benzo[c]carbazoles

2,2′-Diamino-1,1′-biaryls were found to undergo ring-closure condensation reaction to afford benzo[c]carbazoles in good to excellent yield. Coupled with the synthesis of 2,2′-biaryldiamines from diaryl hydrazides via [3,3]-sigmatropic rearrangement, it constitutes a new efficient synthetic method for benzo[c]carbazoles and related compounds.