Mario Anastasia

Lipase-catalysed chemoselective monoacetylation of hydroxyalkylphenols and chemoselective removal of a single acetyl group from their diacetates

Abstract It was demonstrated that Pseudomonas cepacia PS lipase adsorbed on Celite, has the ability to catalyse the chemoselective monoacetylation of various hydroxyalkylphenols or the chemoselective removal of a single acetyl group from the corresponding acetate.

Lipase catalysed resolution of (R)- and (S)-1-trimethylsilyl-1-alkyn-3-ols: useful intermediates for the synthesis of optically active γ-lactones

Abstract Various ( R )- and ( S )-1-trimethylsilyl-1-alkyn-3-ols, chiral building units useful for the synthesis of biologically active compounds, have been efficiently resolved by enantioselective acetylation mediated by immobilized lipase PS. The resolution is applied to the synthesis of ( R )- and ( S )-5-octyl-2-(5H)-furanones.

Structural requirements of aldehydes produced in LPO for the activation of the heat-shock genes in Hela cells

The ability of various aldehydes, some of which are produced in lipid peroxidation, to effect heat-shock gene expression and heat-shock proteins synthesis was evaluated in HeLa cells. Only (E)-4-hydroxyalk-2-enals were active both in racemic and homochiral form. Between the reported primary metabolic products of (E)-4-hydroxynon-2-enal, only the glutathione conjugates were active, whereas (E)-4-hydroxynon-2-enoic acid and 2-nonen-1,4-diol were inactive. Also, unnatural (E)-5-hydroxynon-2-enal and (E)-5-hydroxyhex-2-enal were active, whereas (E)-6-hydroxynon-2-enal was inactive. Thus, it was established that the active aldehydic compounds must possess an (E)-2 double bond and an hydroxy group in a position suitable for the formation of a cyclic hemiacetal in a possible adduct of these aldehydes with proteins. An irreversible binding to proteins could be the first step of the mechanism by which these compounds exert their biological activity.

Epimerization of α- to β-C-glucopyranosides under mild basic conditions

A number of β-C-glucopyranosides having an activated methylene or methine group bonded to the anomeric carbon are obtainable in quantitative yield from the corresponding α-isomers by simple equilibration catalysed by various bases at room temperature.

General and Chemoselective N-Transacylation of Secondary Amides by Means of Perfluorinated Anhydrides†

Examples of direct N-transacylations of amides are very rare and lacking in general applicability. For instance, earlier attempts at N-transacylation were performed under harsh conditions. Other procedures required prolonged treatment with an equimolar mixture of trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA; 100 8C, 48 h), 3] or even running the reaction in TFAA followed by the addition of a strong base, reported as necessary to abstract the hydrogen atom in the alpha position to the eliminated acyl group. Finally, some acetanilides were treated with chloroacetyl chloride under acid catalysis of zeolites or AlCl3 at 83 8C for 16 h, or in refluxing pyridine containing dimethylaminopyridine for 5 h. Thus, N-transacylations are usually accomplished by hydrolysis of the acylamides and successive re-acylation of the formed amines, a procedure that does not allow the simultaneous presence, in the amide molecule, of functional groups labile to the basic or acidic conditions of the hydrolysis. 8] Herein, we report the first direct, general, and chemoselective procedure for the N-transacylation of secondary acylamides to their perfluorinated analogues, in high yields, with perfluorinated anhydrides. Remarkably, the perfluorinated amide formed could then be directly converted to a different amide by simple treatment with the desired acyl chloride, followed by a very mild aqueous process of the reaction mixture. Our work originated while studying sialic acid 1,7-lactone 1a. Surprisingly, on reacting the lactone 1 a with heptafluorobutyric anhydride (HFBAA) to volatilize it (135 8C for 5 min, in CH3CN), [10] we did not obtain the expected derivative 1b but the lactone 2b, which could be quantitatively transformed into lactone 2a by treatment of the reaction mixture with methanol at room temperature. Prompted by these initial results, we explored the scope of this new reaction (Table 1). Because of the particular utility of the reaction in carbohydrate chemistry, we started with some sialic acid and amido sugar derivatives of interest in organic synthesis and in biological studies. In particular, we were interested in testing molecules containing groups labile to the commonly used conditions of amide hydrolysis and reacylation. In effect, our reaction conditions allowed the successful N-transacylation of several compounds containing a great variety of functional groups (often within the same molecule), such as hydroxy groups, lactones, benzyloxycarbonyls (OCbz), methyl esters, acetates, tert-butyldimethylsilyl (TBDMS) groups, and acyclic and cyclic acetals as their 2-methoxyethoxymethyl (MEM), methyl, and benzylidene derivatives (Table 1, entries 1–18). Moreover, to test possible anomerizations resulting from the perfluorinated acid liberated in the reaction, we tested aand b-glycosidic compounds as well as a b-disaccharide. Finally, we selected carbohydrates with an equatorial or an axial acetamido group, to test the possible influence of the amide geometry. The study was first performed with HFBAA, then the reaction was repeated on some representative samples with TFAA, which gave comparable results (Table 1, entries 3, 13, 14, and 17). In all cases, except for entry 7, the reaction occurred in good yields, chemoselectively, and involving exclusively the amido group independently of its equatorial or axial geometry. Other functional groups present in the treated compounds were conserved, with the exception of free hydroxy, alcoholic, or acetalic groups, which, as expected, were perfluoroacylated (mass spectrometry (MS) and NMR evidence) under the reaction conditions employed. However, they could be easily regenerated by simple, short treatment of the crude reaction mixture with a solution of aqueous TFA in THF. Only acyclic acetals appeared to be labile under the reaction conditions, as observed for the MEM group (Table 1, entry 7). Remarkably, analysis of the H NMR spectra of compounds 4, 6, 8, 10, 12, 14, and 16 clearly showed in all cases that the reaction does not modify the configuration of the anomeric centers (see the Supporting Information). The anomeric geometry for the sialic acid derivative 8a, which lacks the anomeric proton, was established on the basis of the values of the heteronuclear vicinal coupling constant (JC1,H3ax and JC2,H3ax). [12, 13]

Synthesis of all four possible stereoisomers of 5-hydroxylysine

Abstract A simple protocol for the transformation of l - and d -glutamic acids into the enantiopure forms of all four isomers of 5-hydroxylysine is described.

A simple and convenient transformation of l-lysine into pyridinoline and deoxypyridinoline, two collagen cross-links of biochemical interest

Abstract Starting from l -lysine as the only chiral building block, pyridinoline and deoxypyridinoline are efficiently synthesised, thus mimicking the postranscriptional formation of these collagen cross-links.

Quantification of N-acetyl- and N-glycolylneuraminic acids by a stable isotope dilution assay using high-performance liquid chromatography-tandem mass spectrometry.

The present report describes a method for the quantification of N-acetyl- and N-glycolylneuraminic acids without any derivatization, using their (13)C(3)-isotopologues as internal standards and a C(18) reversed-phase column modified by decylboronic acid which allows for the first time a complete chromatographic separation between the two analytes. The method is based on high-performance liquid chromatographic coupled with electrospray ion-trap mass spectrometry. The limit of quantification of the method is 0.1mg/L (2.0ng on column) for both analytes. The calibration curves are linear for both sialic acids over the range of 0.1-80mg/L (2.0-1600ng on column) with a correlation coefficient greater than 0.997. The proposed method was applied to the quantitative determination of sialic acids released from fetuin as a model of glycoproteins.

Preparation of (R)- and (S)-(E)-4-hydroxy-2-unsaturated acids by asymmetric hydrolysis of their racemic esters

Abstract Several optically active ( R )- and ( S )-( E )-4-hydroxyalk-2-enoic acids, metabolites of bioactive compounds of lipid peroxidation, were prepared from the corresponding racemic methyl esters by enantioselective hydrolysis mediated by porcine pancreas lipase and porcine liver esterase.

Synthesis of (2R,3S,22S,23S)-2,3,22,23-tetrahydroxy-B-homo-7-aza-5α-stigmastan-6-one, an aza-analogue of homobrassinolide

(2R,3S,22S,23S)-2,3,22,23-Tetrahydroxy-B-homo-7-aza-5α-stigmastan-6-one, an aza-analogue of homobrassinolide, has been synthesized starting with 5α-stigmasta-2,22-dien-6-one. Osmylation of the trimethylsilyl enol ether of this dienone afforded (2R,3S,7S,22S,23S)-2,3,7,22,23-pentahydroxy-5α-stigmastan-6-one, which by oxidation of the acyloin group, after protection of the glycolic systems, afforded (by esterification) an aldehydo ester, which is the key intermediate for the production of the final compound by reductive amination.