Anna Rencurosi

Efficient continuous flow synthesis of hydroxamic acids and suberoylanilide hydroxamic acid preparation.

A continuous flow tubing reactor can be used to readily transform methyl or ethyl carboxylic esters into the corresponding hydroxamic acids. Flow rate, reactor volume, and temperature were optimized for the preparation of a small collection of hydroxamic acids. Synthetic advantages were identified as an increased reaction rate and higher product purity. This method was also successfully applied to the multistep preparation of suberoylanilide hydroxamic acid, a potent HDAC inhibitor used in anticancer therapy.

Synthesis of (+)‐Dumetorine and Congeners by Using Flow Chemistry Technologies

An efficient total synthesis of the natural alkaloid (+)-dumetorine by using flow technology is described. The process entailed five separate steps starting from the enantiopure (S)-2-(piperidin-2-yl)ethanol 4 with 29% overall yield. Most of the reactions were carried out by exploiting solvent superheating and by using packed columns of immobilized reagents or scavengers to minimize handling. New protocols for performing classical reactions under continuous flow are disclosed: the ring-closing metathesis reaction with a novel polyethylene glycol-supported Hoveyda catalyst and the unprecedented flow deprotection/Eschweiler-Clarke methylation sequence. The new protocols developed for the synthesis of (+)-dumetorine were applied to the synthesis of its simplified natural congeners (-)-sedamine and (+)-sedridine.

Probing specific protein recognition by size-controlled glycosylated cyclodextrin nanoassemblies

The balance between hydrophobic and hydrophilic components in amphiphilic β-cyclodextrins, targeted by receptor specific groups (SC6CDGlc, SC6CDGal, SC16CDGlc, SC16CDGal), sensitively influences the structural properties of these systems. The different amphiphilic features of single cyclodextrins generate micellar aggregates and vesicles with an internal aqueous compartment able to encapsulate guests, such as rhodamine 6G. Small-angle light scattering (SAXS), cryo-TEM and AFM investigations describe the size and shape of these self-organized glycoligands. Recognition of the nanoassemblies by a specific receptor has effectively been demonstrated by means of time resolved fluorescence and is addressed in water by the morphological properties of cyclodextrin aggregates. Exclusively galactosylated thiohexyl-cyclodextrin binds specifically lectin from Pseudomonas aeruginosa. β-D-Galactose competes with galactosylated cyclodextrin aggregates by inhibiting lectin binding but does not affect the mesoscopic environment of the protein. The better selectivity of the less hydrophobic cyclodextrins towards lectin should probably be ascribed to the morphology (size and shape) of these cyclodextrin aggregates. The recognition properties of this particular cyclodextrin (SC6CDGal) are probably due to the presence of small micelles which interact more efficiently with the lectin binding site. The modulation of the hydrophobic–hydrophilic balance of the macrocycle labelled with targeting groups allows the design of “active” nanosized carriers for drug delivery.

Cyclodextrin nanoaggregates and their assembly with protein: a spectroscopic investigation

Light scattering and time-resolved fluorescence spectroscopy results showed that specially designed amphiphilic cyclodextrins are able to bind a specific protein, PA-I lectin. When containing a galactosyl group, the self-assembled cyclodextrins interact with the protein affecting the dynamical properties of the system and the fluorescence lifetimes (as well as the fluorescence anisotropy) of the protein itself. The self-assembled cyclodextrins containing a glucosyl group, on the other hand, do not induce any change in these measured quantities, suggesting no interaction with protein. This binding capability of galactosyl-modified cyclodextrins offers perspectives on exploiting self-assembled supramolecular structures as nano-carriers to deliver drugs to target tissues.

Modeling of synthetic phosphono and carba analogues of N-acetyl-α-D-mannosamine 1-phosphate, the repeating unit of the capsular polysaccharide from Neisseria meningitidis serovar A

The conformational behavior of methyl (2-acetamido-2-deoxy-alpha-d-mannopyranosyl)phosphate 1, and its analogues, methyl C-(2-acetamido-2-deoxy-alpha-d-mannopyranosyl)methanephosphonate 2 and methyl O-(2-acetamido-2-deoxy-5a-carba-alpha-d-mannopyranosyl)phosphate , where a methylene group replaces, respectively, the anomeric and the pyranose oxygen atom, was investigated at the B3LYP/6-311+G(d,p) level [6-311+G(2df,p) for the phosphorus atom]. The energy of the optimized structures was recalculated using the continuum solvent model C-PCM choosing water as the solvent. The compounds exhibited several populated conformations, but they all showed a marked preference for the (4)C(1) geometry of the pyranose ring; this preference was almost complete for 1, very large for the phosphono analogue 2, and large for the carba analogue 3. To give experimental support to these results, compounds 2 and 3 were synthesized and characterized by NMR spectroscopy. The comparison of the theoretical and experimental vicinal coupling constants confirmed the marked preference for the (4)C(1) geometry in the case of 2 and suggested that the same holds true for compound 3.

HRMAS NMR analysis in neat ionic liquids: a powerful tool to investigate complex organic molecules and monitor chemical reactions

The high resolution magic angle spinning (HRMAS) NMR technique proved to be an effective tool for the analysis of organic solutes and for the observation of an organic reaction in neat ionic liquids.

IMPROVEMENT ON LIPASE CATALYSED REGIOSELECTIVE O-ACYLATION OF LACTOSE:A CONVENIENT RUOTE TO 2′-O- FUCOSYLLACTOSE[1]

Although enormous progress has been made in the past ten years, the synthesis of complex carbohydrates still remains a severe problem. Conventional syntheses of these molecules often dictate multiple protections and deprotections of various hydroxyl groups, dramatically increasing the number of steps required. On the other hand, enzymes offer the opportunity to carry out cheap, highly chemo and regioselective transformations, providing new approaches to tackle many synthetic problems encountered in carbohydrate synthesis. In particular, lipases allow highly regioselective O-acylations. Therefore, a growing interest in enzymatic manipulation of protecting groups for the synthesis of oligosaccharides has been developed during recent years. Recently, we reported on the use of lipase catalysed acylation for designing useful building blocks in oligosaccharide synthesis. Excellent selectivity for 6 O-acylation was observed on various disaccharidic substrates (such as lactose, maltose and cellobiose) using different acylating agents, Candida antarctica lipase being the best biocatalyst. However, our procedure contained a main drawback: the high polarity of the sugar substrates required the use of tert-amyl alcohol as a solvent, whose high boiling point made the work up of the reaction mixture quite laborious, thus rendering the method impractical. An important improvement J. CARBOHYDRATE CHEMISTRY, 20(7&8), 761–765 (2001)