Electrospray ionization ion trap multiple-stage mass spectrometric fragmentation pathways of leucine and isoleucine: an ab initio computational study

We recently demonstrated the possibility to distinguish between leucine and isoleucine in several tryptic peptides by means of consecutive tandem mass steps (Armirotti et al. J. Am. Soc. Mass Spectrom. 2007; 18: 57), exploiting a gas-phase rearrangement of the immonium ion of Ile. In the present paper we explore the tandem mass spectrometric behaviour of the two amino acids. We propose a plausible structure for the diagnostic m/z 69 ion of Ile, that was reported for the first time in 1996 (Hulst and Kientz J. Mass. Spectrom. 1996; 31: 1188), and we explain why its formation is favoured with respect to Leu. Our conclusions are supported by ab initio quantum chemistry calcultations and isotope-labelled standards experiments

An improved method for simultaneous analysis of aminothiols in human plasma by high performance liquid chromatography with fluorescence detection

A new method for the simultaneous determination of d- and l-lactic acid in human plasma has been developed using high-performance liquid chromatography (HPLC) with fluorescence detection. This method is based on the reaction of lactic acid with (2S)-2-amino-3-methyl-1-[4-(7-nitro-benzo-2,1,3-oxadiazol-4-yl)-piperazin-1-yl]-butan-1-one (NBD-PZ-Val) in the presence of O-(7-azobenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and N-ethyldiisopropylamine (DIEA) to produce fluorescent diastereomeric derivatives that were easily monitored fluorimetrically at \uf06cex = 490nm and \uf06cem = 532 nm. The separation was achieved by use of a C18 analytical column (Synergy Hydro 150mm 73mm i.d., 4\uf06dm). The calibration curve was linear over the on-column concentration range of 10\u2013200 \uf06dmol/L for d-lactic acid and 0.5\u20134.0 mmol/L for l-lactic acid. The sensitivity was good with a limit of detection of 5.24 mol/L for d-lactic acid and 0.15 mmol/L for l-lactic acid. The analytical method was successfully applied to human plasma samples from normal healthy subjects

A straight access to functionalized carbazoles by tandem reaction between indole and nitrobutadienes

As a continuation of our research on the synthetic exploitation of the nitrobutadienic building-blocks obtained from the ring-opening of nitrothiophenes, we herein report about their reaction with the \u3c0-nucleophilic indole. Thanks to their double Michael-acceptor nature, 2,3-dinitro and 2-nitro-3-phenylsulfonyl substituted 1,3-butadienes produce poly-functionalized carbazoles through a double (inter-+intra-molecular) conjugate addition, followed by aromatization of the newly built ring. Significance is attached to the results obtained in fluorinated solvents such as trifluoroethanol, whereby a mild process, with no need for catalysis, overcomes some practical difficulties otherwise limiting the scope of the reaction. Besides the mechanistic aspects, the reaction encompasses motifs for a synthetic interest, mainly in the field of further-tunable arylcarbazoles endowed with predictable applicative properties, e.g., as fluorescent devices

On the behavior of bis(sulfonyl)nitrobutadienes towards primary amines: a convenient access to 1-alkyl-2-aryl-4-(phenylsulfonyl)pyrroles

The conjugated bis(sulfonyl)nitrobutadienes 1 undergo, with primary amines, competitive MeSO2 replacement [vinylic substitution at C(1)] versus aza-Michael addition to the nitroethenyl C(3)–C(4) double bond. The latter pathway eventually leads to the trisubstituted pyrroles 2 and conditions have been optimized in order to maximize the yield of such polyfunctionalized heterocycles. Interestingly, in trifluoroethanol tetrasubstituted pyrroles 7 are also formed, thanks to a final aromatization via oxidation by ‘endogenous’ nitrite

Highly-substituted pyrazoles and pyridazines by MIRC reactions of hydrazone anions and nitrobutadienic fragments

In prosecution of the synthetic exploitation of nitrobutadienes deriving from the initial ring-opening of nitrothiophenes, their multifaceted behavior \ufb01nds a further clear-cut example in their Michael-type acceptor reactivity toward the anions of a-oxohydrazones. Thus, depending on the starting diene, new poly-functionalized pyrazoles are obtained. Furthermore, most interestingly, in one occasion a dichotomy has been observed, depending on the nature of the Michael-type donor, leading with complete selectivity to either 5-member or 6-member N-heterocycles. The outcome encompasses motifs for both mechanistic and synthetic interest, for example, in the \ufb01eld of heterocycles endowed with possible pharmacological/biological activity

Optimised solid phase synthesis of a cystine-linked peptide-PNA chimera

A solid phase synthesis method for a cystine-linked peptide-PNA chimera starting from different modified protectedcystine monomers was developed. This strategy dramatically improved the final yield and the specificity of disulphide bondformation in this kind of oligomers, which are traditionally obtained by liquid phase coupling via oxidation of the two terminalcysteines