Silvestre Buscemi

Ring Transformations of Five-Membered Heterocycles*

Publisher Summary This chapter reviews that ring transformations of heterocycles constitute an interesting area that continues to be of great importance in mechanistic studies and in synthetic design. With reference to five-membered heterocycles, an enormous variety of ring transformations are known and there has always been some difficulty in rationalizing these reactions systematically. A greatly significant classification can be recognized in molecular rearrangements of heteromonocycles that involve the participation of a given number of side-chain atoms in the new ring formation, including special rearrangements where interchanges of annular atoms simply occur. This review is concerned with the rearrangements of five-membered heterocycles represented by the generalized pattern 5→ 6, where W pivotal center is a nitrogen (W=N), sulfur (W=S), or carbon atom (W=C), and the side-chain contains three or four participating atoms.

Study on the thermotropic properties of highly fluorinated 1,2,4-oxadiazolylpyridinium salts and their perspective applications as ionic liquid crystals

A new series of fluorinated salts, iodides and trifluoromethanesulfonates, was synthesized from perfluoroalkylated 1,2,4-oxadiazolylpyridines. Their thermotropic properties were investigated by combined temperature resolved small angle and wide angle X-ray scattering, differential scanning calorimetry and polarised optical microscopy. The UV–visible and photoluminescence properties were studied for all compounds. The results showed for two compounds the existence of an enantiotropic mesomorphic smectic liquid crystal phase. All iodides showed thermochromism phenomena suggesting prospective applications in optoelectronics.

Hsp60, a novel target for antitumor therapy: Structure-function features and prospective drugs design

Heat shock protein 60 kDa (Hsp60) is a chaperone classically believed to be involved in assisting the correct folding of other mitochondrial proteins. Hsp60 also plays a role in cytoprotection against cell stressors, displaying for example, antiapoptotic potential. Despite the plethora of studies devoted to the mechanism of Hsp60s function, especially in prokaryotes, fundamental issues still remain unexplored, including the definition of its role in cancer. Key questions still unanswered pertain to the differences in structure-function features that might exist between the well-studied prokaryotic GroEL and the largely unexplored eukaryotic Hsp60 proteins. In this article we discuss these differences in sequence, structure, and roles of Hsp60, focusing on the human ortholog with the view of devising compounds to block its ability to favour tumor-cell growth and survival. Compounds currently known to directly or indirectly affect Hsp60 functions, such as protein folding, HIF-1α accumulation, or Hsp60-induced cell proliferation, are discussed along with strategies that might prove effective for developing Hsp60-targeting drugs for anticancer therapy.

Experimental and DFT studies on competitive heterocyclic rearrangements. 3. A cascade isoxazole-1,2,4-oxadiazole-oxazole rearrangement.

The thermal rearrangements of 3-acylamino-5-methylisoxazoles 1 have been investigated under basic and neutral conditions and interpreted with the support of computational data. The density functional theory (DFT) study on the competitive routes available for the base-catalyzed thermal rearrangement of isoxazoles 1 showed that the Boulton-Katritzky (BK) rearrangement, producing the less stable 3-acetonyl-1,2,4-oxadiazoles 5, is a much more favored process than either the migration-nucleophilic attack-cyclization (MNAC) or the ring contraction-ring expansion (RCRE). In turn, an increase in reaction temperature will promote the MNAC of oxadiazoles 5, producing the more stable 2-acylaminooxazoles 8. The thermal rearrangement of 3-acylaminoisoxazoles 1 into oxazoles 8 can therefore be interpreted in terms of a cascade BK-MNAC rearrangement involving 3-acetonyl-1,2,4-oxadiazoles 5 as ancillary intermediates.

THE SYNTHESIS OF FLUORINATED HETEROAROMATIC COMPOUNDS. PART 1. FIVE-MEMBERED RINGS WITH MORE THAN TWO HETEROATOMS. A REVIEW

INTRODUCTION 449 I. OXADIAZOLES 450 1. 1,2,4-Oxadiazoles 451 a) The Amidoxime Route 451 b) The Cycloaddition Route 456 c) The Ring-rearrangement Route 457 2. 1,3,4-Oxadiazoles 460 a) The Diacylhydrazine Route 461 b) The Acyl-tetrazole Rearrangement Route 462 c) The Photoinduced Ring-rearrangement Approach 464 3. 1,2,5-Oxadiazoles 465 II. THIADIAZOLES 466 1. 1,2,4-Thiadiazoles 466 2. 1,3,4-Thiadiazoles 468 3. 1,2,5-Thiadiazoles 471 III. TRIAZOLES 473 1. 1,2,4-Triazoles 473 a) Heterocyclization Reactions 474 b) Ring-rearrangement Reactions 479 2. 1,2,3-Triazoles 481 a) Heterocyclization Reactions 482 IV. TETRAZOLES 487 V. CONCLUDING REMARKS 492 REFERENCES 492 ORGANIC PREPARATIONS AND PROCEDURES INT., 37 (5), 447-506 (2005)

Perfluorocarbon functionalized hyaluronic acid derivatives as oxygenating systems for cell culture

A set of new hyaluronic acid (HA) derivatives was obtained by binding fluorinated oxadiazole (OXA) moieties to an amino derivative of the polysaccharide (HA-EDA). The obtained HA-EDA-OXA biomaterials are potentially able to improve oxygenation into a scaffold for tissue engineering purposes. The oxygen solubility in aqueous dispersions of the obtained derivatives showed that polymers were able to improve oxygen uptake and maintenance in the medium. The HA-EDA-OXA was employed to form a hydrogel in situ by reaction with a vinyl sulphone derivative of inulin, under physiological conditions. The influence of the presence of OXA moieties on the mechanical properties of the obtained hydrogels as well as on the metabolic activity of incorporated primary fibroblasts was investigated. The produced HA-EDA-OXA biomaterials were able to promote cell growth under hypoxic conditions.

Exploiting the CNC side chain in heterocyclic rearrangements: synthesis of 4(5)-acylamino-imidazoles.

A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

Synthesis of Amino-1,2,4-triazoles by Reductive ANRORC Rearrangements of 1,2,4-Oxadiazoles

The reaction of various 1,2,4-oxadiazoles with an excess of hydrazine in DMF has been investigated. 3-Amino-1,2,4-triazoles are produced through a reductive ANRORC pathway consisting of the addition of hydrazine to the 1,2,4-oxadiazole followed by ring-opening, ring-closure, and final reduction of the 3-hydroxylamino-1,2,4-triazole intermediate. The general applicability of 1,2,4-oxadiazoles ANRORC reactivity is demonstrated also in the absence of C(5)-linked electron-withdrawing groups.

Fluoro heterocycles. A photochemical methodology for the synthesis of 3-amino- and 3-(N-alkylamino)-5-perfluoroalkyl-1,2,4-oxadiazoles

Abstract A photochemical methodology for the synthesis of perfluoroalkyl-1,2,4-oxadiazoles has been described. 3-Amino- and 3-( N -alkylamino)-5-perfluoroalkyl-1,2,4-oxadiazoles have been prepared by irradiation of 3-perfluoroalkanoylamino-4-phenyl-1,2,5-oxadiazoles (furazans) at λ =313 nm in methanol and in the presence of ammonia or primary aliphatic amines.

1,2,4-Oxadiazole Rearrangements Involving an NNC Side-Chain Sequence

The thermal rearrangement of N-1,2,4-oxadiazol-3-yl-hydrazones into 1,2,4-triazole derivatives is reported. This represents the first example of a three-atom side-chain rearrangement involving an NNC sequence linked at the C(3) of the oxadiazole. The reactions carried out under solvent-free conditions produced good to high yields of the final products.