Vincenzo Piccialli

OsO4-Catalyzed oxidative cyclization of geranyl and neryl acetate to cis-2,5-bis(hydroxymethyl)tetrahydrofurans

OsO4 catalyzes the oxidative cyclization of the 1,5-dienes geranyl acetate (1) and neryl acetate (2) to the cis-2,5-bis(hydroxymethyl)tetrahydrofurans 3 and 4 respectively, in the presence of NaIO4 as cooxidant in DMF. The reaction is stereospecific and proceeds with the sequential syn addition to both double bonds of the starting materials. The observed stereoselectivity can be explained by invoking the intermediacy of a square-based pyramidal osmium (VI) diester (5) that has been isolated and characterized. Evidence is reported that this substance is indeed an intermediate in the transformation of 1 to 3.

Improved RuO4-catalysed oxidative cyclisation of geraniol-type 1,5-dienes to cis-2,5-bis(hydroxymethyl)tetrahydrofuranyldiols

Abstract The oxidation of some representative 1,5-dienes based on the geraniol and nerol carbon skeletons, namely geranyl acetate ( 1 ), geranic acid methyl ester ( 5 ), trans , trans -2,6-dimethyl-2,6-octadiene-1,8-diol diacetate ( 9 ), neryl acetate ( 13 ) and neroic acid methyl ester ( 16 ), has been performed using catalytic amounts of RuO 4 (from RuO 2 ·2H 2 O, 4%) in the presence of NaIO 4 (4 equiv.) as co-oxidant in the solvent mixture EtOAc/CH 3 CN/H 2 O (3:3:1) at 0°C for 4 min. These conditions assure a degree of stereoselectivity for the geraniol-type dienes higher than that obtained under the Sharpless conditions [RuCl 3 ·(H 2 O) n (2.2%), NaIO 4 (3.1 equiv.), CCl 4 /CH 3 CN/H 2 O (2:2:3), 0°C], furnishing the cis - and trans -THF diol products in 62–70 and 6–9% yields, respectively. In addition, the amount of the cis -THF, C-2 overoxidised, product is strongly reduced (2–7%). A comparison with the related MnO 4 − -induced process, tested on the same substrates, was made.

Studies towards the synthesis of polyoxygenated steroids. Reaction of some tri- and tetra-substituted monoene steroids with RuO4

Abstract The course of the reaction of ruthenium tetroxide with some tri- and tetra-substituted nuclear monoene steroids, namely δ 4 , δ 5 , δ 7 and δ 8(14) -steroids, has been investigated in acetone-water or carbon tetrachloride as solvent systems using stoichiometric amounts of the oxidant. In contrast with results previously reported for RuO 4 oxidations, we found that trisubstituted double bonds gave α-hydroxy ketones and/or 1,2-diols rather than the expected products deriving from the scission of the carbon-carbon double bond. Scission of the double bond indeed occurs when fully substituted steroidal alkenes are oxidized. Only in the case of the δ 8(14) -steroid, an allylic oxidation product wa obtained in addition to the scission product. The change in the solvent system seems to profoundly affect the course of the reaction.

Nitrogenous sesquiterpenes from the marine sponge acanthella acuta: three new isocyanide-isothiocyanate pairs

Abstract The isolation and the structure elucidation of six new nitrogenous sesquiterpenes ( 3 – 8 ) from the marine sponge Acanthella acuta are described. A complete H- and -13C-NMR assignment for the new metabolites, which form three new isocyanide-isothiocyanate pairs, was accomplished with the aid of carbon-proton shift correlated 2D-NMR experiments.

Ruthenium Tetroxide and Perruthenate Chemistry. Recent Advances and Related Transformations Mediated by Other Transition Metal Oxo-species

In the last years ruthenium tetroxide is increasingly being used in organic synthesis. Thanks to the fine tuning of the reaction conditions, including pH control of the medium and the use of a wider range of co-oxidants, this species has proven to be a reagent able to catalyse useful synthetic transformations which are either a valuable alternative to established methods or even, in some cases, the method of choice. Protocols for oxidation of hydrocarbons, oxidative cleavage of C–C double bonds, even stopping the process at the aldehyde stage, oxidative cleavage of terminal and internal alkynes, oxidation of alcohols to carboxylic acids, dihydroxylation of alkenes, oxidative degradation of phenyl and other heteroaromatic nuclei, oxidative cyclization of dienes, have now reached a good level of improvement and are more and more included into complex synthetic sequences. The perruthenate ion is a ruthenium (VII) oxo-species. Since its introduction in the mid-eighties, tetrapropylammonium perruthenate (TPAP) has reached a great popularity among organic chemists and it is mostly employed in catalytic amounts in conjunction with N-methylmorpholine N-oxide (NMO) for the mild oxidation of primary and secondary alcohols to carbonyl compounds. Its use in the oxidation of other functionalities is known and recently, its utility in new synthetic transformations has been demonstrated. New processes, synthetic applications, theoretical studies and unusual transformations, published in the last eight years (2006–2013), in the chemistry of these two oxo-species, will be covered in this review with the aim of offering a clear picture of their reactivity. When appropriate, related oxidative transformations mediated by other metal oxo-species will be presented to highlight similarities and differences. An historical overview of some aspects of the ruthenium tetroxide chemistry will be presented as well.

Two new 9,11-secosterols from the marine sponge Spongia officinalis. Synthesis of 9,11-seco-3β,6α,11-trihydroxy-5α-cholest-7-en-9-one

Abstract Two new 9,11-secosterol, 9,11-seco-3β,6α,11-trihydroxy-5α-cholest-7-en-9-one (2) and 9,11-seco-3β,6α,11-trihydroxy-24-methylene-5α-cholest-7-en-9-one (3) , have been isolated from the marine sponge Spongia officinalis and their structures elucidated by analysis of spectral data including 1 H nuclear magnetic resonance correlation spectroscopy (COSY) experiments. Partial synthesis of 2 starting from 3β,6α-dihydroxy-9-oxo-9,11-seco-5α-cholest-7-en-11-al (1) confirmed the structure assignment .

The Anti-Proliferative Effect of L-Carnosine Correlates with a Decreased Expression of Hypoxia Inducible Factor 1 alpha in Human Colon Cancer Cells

In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases.

RuO4-catalysed oxidative cyclisation of 1,6-dienes to trans-2,6-bis(hydroxymethyl)tetrahydropyranyldiols. A novel stereoselective process

Abstract RuO4 catalyses the stereoselective oxidative cyclisation of the 1,6-dienes, 7-methyl-1,6-octadiene and 1,6-heptadiene, to the corresponding trans-2,6-bis(hydroxymethyl)tetrahydropyranyldiols, in the presence of NaIO4 as primary oxidant, in EtOAc:CH3CN:H2O (3:3:1) at 0°C for 4 min. A mechanistic hypothesis explaining the observed trans-2,6-stereochemical control is formulated.

Evidence for the existence of a cyclic ruthenium (VI) diester as an intermediate in the oxidative scission of (−)-α-pinene with RuO4☆

Abstract The reaction of (−)-α-pinene ( 1 ) with RuO 4 in CCl 4 at room temperature affords the ketoaldehyde 3 as the sole product. Evidence is reported that the oxidative scission of the olefinic substrate to 3 proceeds through a ruthenium (VI) diester intermediate for which we propose structure 2 on the basis of spectral evidence and comparison with the osmium-containing analogue of 2 , synthesised by reaction of (−)-α-pinene with OsO 4 in dioxane and whose structure has been determinated by single crystal X-ray diffraction analysis. Compound 2 was also shown to be an intermediate compound in the RuO 4 oxidation of (−)-α-pinene performed in acetone-water (2:1) which gives α-ketol 4 as the sole oxidation product.

New anti-HIV aptamers based on tetra-end-linked DNA G-quadruplexes: effect of the base sequence on anti-HIV activity

This communication reports on the synthesis and biophysical, biological and SAR studies of a small library of new anti-HIV aptamers based on the tetra-end-linked G-quadruplex structure. The new aptamers showed EC(50) values against HIV-1 in the range of 0.04-0.15 μM as well as affinities for the HIV-1 gp120 envelope in the same order of magnitude.