Cascade and multicomponent synthesis of structurally diverse 2-(pyrazol-3-yl)pyridines and polysubstituted pyrazoles.

The cascade reaction between N-tosylhydrazones and 2-alkynylpyridines leads to 2-(pyrazol-3-yl)pyridines, important structural motifs in ligands for transition metals and bioactive molecules. When the reaction is conducted with 2,6-diethynylpyridine, the important 2,6-bis(pyrazolyl)pyridines are obtained, featuring the arrangement of tridentate and also pentadentate ligands. A novel three-component version of the reaction has been designed, which involves the use of α-bromo-N-tosylhydrazones, alkynylpyridines and NH-azoles.

Synthesis of 1,3-diaryl-3-trifluoromethylcyclopropenes by transition-metal-free reaction of 2,2,2-trifluoroacetophenone tosylhydrazones with alkynes: the effect of the trifluoromethyl group.

1,3-Diaryl-3-trifluoromethylcyclopropenes and 2-aryl- or 2-alkyl-1,3-diaryl-3-trifluoromethylcyclopropenes are prepared in a very simple way by reaction between 1,1,1-trifluoroacetophenone tosylhydrazones and terminal or internal alkynes, respectively, in a base promoted process that does not require the presence of any metal catalyst. The essential role of the trifluoromethyl group, which enables the formation of the cyclopropenes instead of the expected pyrazoles, has been computationally investigated, suggesting the participation of a free carbene.

An Autocatalytic System of Photooxidation-Driven Substitution Reactions on a Fe(II)4L6 Cage Framework.

The functions of life are accomplished by systems exhibiting nonlinear kinetics: autocatalysis, in particular, is integral to the signal amplification that allows for biological information processing. Novel synthetic autocatalytic systems provide a foundation for the design of artificial chemical networks capable of carrying out complex functions. Here we report a set of Fe(II)4L6 cages containing BODIPY chromophores having tuneable photosensitizing properties.

Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency.

Background: SERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Mutations in SERPINA1 gene cause AAT deficiency and predispose individuals to early-onset emphysema and liver diseases. Expression of the SERPINA1 gene is regulated by different promoters and alternative splicing events among non-coding exons 1A, 1B and 1C.

Selective encapsulation and sequential release of guests within a self-sorting mixture of three tetrahedral cages.

A mixture of two triamines, one diamine, 2-formylpyridine and a Zn(II) salt was found to self-sort, cleanly producing a mixture of three different tetrahedral cages. Each cage bound one of three guests selectively. These guests could be released in a specific sequence following the addition of 4-methoxyaniline, which reacted with the cages, opening each in turn and releasing its guest.

Chirality-driven folding of short β-lactam pseudopeptides.

Novel enantiopure pseudopeptide models containing a central -(β-lactam)-(Aa)- scaffold characterized by the combined presence of an α-alkyl-α-amino-β-lactam (i+1) residue and a α-substituted (i + 2) amino acid have been readily synthesized from α-alkyl serines. The conformational analysis of such β-lactam pseudopeptides conducted in CDCl(3) and DMSO-d(6) solutions using 1D- and 2D-NMR techniques revealed an equilibrium between β-II turn and γ-turn conformers, which was ultimately modulated by the relative configuration of the -(β-lactam)-(Aa)- residues. Long-range chiral effects on the α-lactam pseudopeptide conformers were also found when two (i) and (i + 3) chiral residues were attached to the termini of a central -(β-lactam)-(Aib)- segment.

Synthesis of beta-lactam scaffolds for ditopic peptidomimetics.

[reaction: see text] Ring opening of alpha-substituted-alpha-methoxycarbonyl-N-nosylaziridines provides a practical access to enantiopure alpha,alpha'-disubstituted beta-lactam scaffolds, novel types of ditopic reverse turn surrogates. The procedure is general, short, and high yielding and starts from handy alpha-substituted serinates and alpha-amino acid derivatives.

Synthesis of type II beta-turn surrogate dipeptides based on syn-alpha-amino-alpha,beta-dialkyl-beta-lactams.

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochemical determinant of the alpha-alkylation reaction in beta-branched alpha-phenyloxazolidinyl- or alpha-diphenyloxazolidinyl-beta-lactams and provides the first stereocontrolled access to syn-alpha-amino-alpha,beta-dialkyl(aryl)-beta-lactams. These products are readily transformed into type II beta-turn mimetic surrogates 2B. [reaction: see text]