Juan Carlos Estévez

2-Benzylidene-1-indanones constitute a family of heterocyclic compounds with a wide range of pharmacological and material applications. Here we present preliminary results of new chemistry in this field. An acid-mediated aldolic condensation of 1-indanone with o-nitrobenzaldehyde provided (E)-2-(2-nitrobenzylidene)-2,3-dihydro-1H-inden-1-one, which, when subjected to catalytic hydrogenation, led directly to 4b,10,10a,11-tetrahydro-5H-indeno[1,2-b]quinoline, as a result of several successive spontaneous reactions. On the other hand, a base-mediated aldolic condensation of 1-indanone with o-methoxycarbonylbenzaldehyde yielded methyl (E)-2-((1-oxo-1,3-dihydro-2H-inden-2-ylidene)methyl)benzoate which, when treated with LDA, led to the formation of 1′-(diisopropylamino)-2,2′-spirobi[indene]-1,3′(1′H,3H)-dione.

A ne stereocontrolled nitro sugar-mediated synthesis of polyhydroxylated β-amino acids is reported. The key step of this approach is a Michael addition of the lithium salt of tris(phenylthio)methane (a carboxyl synthetic equivalent) to sugar nitro olefins. This is followed by the generation of the amino acid functionality by the transformation of the tris(phenylthio)methyl substituent into the carboxylic acid functionality and the reduction of the nitro group to an amino group.

A synthesis of the five membered iminosugar DAB and a divergent synthesis of the six membered iminosugar 1‐dehydromannojirimycin (DMJ) and the corresponding sugar imino acid are reported. They involve double nucleophilic displacements of a D‐xylose ditriflate by benzyl carbazate and a D‐glucose ditriflate by allyl amine, respectively. They are followed by a similar protocol consisting of hydrolysis and oxidation or reduction of the resulting bicyclic glycosides. This allowed DMJ to be obtained from the cheap sugar D‐glucose.

A synthesis of the five membered iminosugar DAB and a divergent synthesis of the six membered iminosugar 1-dehydromannojirimycin (DMJ) and the corresponding sugar iminoacid are reported. They involve double nucleophilic displacements of a D-xylose ditriflate by benzyl carbazate and a D-glucose ditriflate by allyl amine, respectively. They are followed by a similar protocol consisting of hydrolysis and oxidation or reduction of the resulting bicyclic glycosides. This allowed DMJ to be obtained from the cheap sugar D-glucose.

The synthesis and organocatalytic properties of (2S,3R,4R)-3,4-bis((tert-butyldimethylsilyl)oxy)pyrrolidine-2-carboxylic acid are reported. Using the aldol condensation of cyclohexanone with p-nitrobenzaldehyde as a model, a yield of 86%, an enantiomeric excess of 99% and a diastereomeric excess of 25:1 were achieved.

We describe the synthesis of trihydroxylated cyclohexane β-amino acids from (−)-shikimic acid, in their cis and trans configuration, and the incorporation of the trans isomer into a trans-2-aminocyclohexanecarboxylic acid peptide chain.

We describe the excellent gelation capabilities of amides derived from trans-cyclohexaneβ-amino acid, demonstrating their great potential to generate lypogels in a wide variety of solvents. Structural factors affecting this behavior, like modifying the balance between their hydrophilic/hydrophobic moieties (by changing their alkyl chain length) or their enantiomeric composition (enantiomerically pure compounds vs. racemic mixtures) were investigated. A comprehensive structural analysis ranging from microscopic arrangements to their macroscopic structures is also discussed

We describe short non-natural peptides that adopt α- and β-turn folds in solution and in the crystal. The peptides are constituted by a core of trans and cis stereoisomers of polyhydroxylated cyclohexane γ-amino acids, flanked by dimers of L-α-alanine, resulting in hybrid hexapeptides with an ααγγαα backbone. DFT calculations and spectroscopic analysis by NMR, CD and FT-IR in solution are consistent with structural changes upon deprotection of certain hydroxyl groups of the central polyhydroxylated γ-amino acids. X-ray diffraction analysis of a crystalline sample revealed a double α-/β-turn that was also identified by NMR spectroscopy in acetonitrile-d3 solution.

We describe the synthesis of trihydroxylated cyclohexane β-amino acids from (–)-shikimic acid, in their cis and trans configuration, and the incorporation of the trans isomer into a trans-2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of trans-2-aminocyclohexanecarboxylic acid. This means that the high degree of substitution of the cyclohexane ring of the new residue is compatible with the adoption of a stable helical secondary structure and opens opportunities for the design of more elaborate peptidic foldamers with oriented polar substituents at selected positions of the cycloalkane residues.