From micellar electrokinetic chromatography to liquid chromatography-mass spectrometry: revisiting the way of analyzing human fluids for the search of desmosines, putative biomarkers of chronic obstructive pulmonary disease.

Desmosine (DES) and isodesmosine are two isomer amino acids unique-to-mature, cross-linked elastin. Based on this feature, they have been discussed as surrogate markers of chronic obstructive pulmonary disease, a disorder characterized by progressive degradation of lung elastin. Despite the development of numerous protocols, detection of DESs in body fluids is still considered to be technically challenging. In fact, owing to the minute concentration of these circulating cross-links, their accurate measurement may be provided only by sophisticated and sensitive techniques. Aim of this article is to present the "history" of the two techniques (MEKC and LC-MS) that, better than others, allowed scientists to "bring their best to the table" in this area. Both of them meet the criteria of (almost) complete automation of the procedure and of the use of more selective and sensitive detection systems. The substantial advantages in terms of precision and accuracy provided by such measurements suggest that the science of DESs is eventually catching up with its promise and the assumption that these candidate biomarkers can be associated to clinical variables holds true.

Micellar electrokinetic chromatography with laser induced detection and liquid chromatography tandem mass-spectrometry-based desmosine assays in urine of patients with Chronic Obstructive Pulmonary Disease: a comparative analysis.

Evidences accumulated over the past years that desmosines could be attractive indicators of elastic fibre degradation in Chronic Obstructive Pulmonary Disease have raised substantial interest with the development of reliable assays to measure their concentration in body fluids. It is a firm belief of researchers working in this field that accurate assessment of desmosine concentration would improve the understanding of elastin metabolism disorders and allow these cross-links to become a useful tool in the diagnosis and clinical management of these diseases. From among the variety of techniques available on the market, HPLC; CE and LC-MS have proved to be successful tools for measuring desmosines in biological fluids. However, differences in the analytical performance of methods may hinder the comparability of data, thus limiting the analytical strength and clinical utility of methods themselves. To address the relative contribution of different factors to the exact quantification of desmosines, the full potential of MEKC-LIF and LC-MS, the two systems that better than others offer more selective and sensitive detection for desmosine analysis, was studied on 56 urine samples. The results of this systematic comparative study underline the significant benefits of LC-MS over MEKC-LIF in terms of precision and sensitivity. Nevertheless, MEKC-LIF could be an attractive alternative in routine laboratories lacking the LC-MS instrumentation and skills to run these methods.

Enantioselective total synthesis of semperoside a.

A versatile and concise strategy has been developed (Scheme 1) for the enantioselective synthesis of semperoside A 1 which is endowed with an unusually glucosylated iridane structure. The crucial step was a Hg(II)-mediated electrophilic heteroatom cyclization of beta-glucoside 4 that readily led to the iridane skeleton while installing the C-2 and C-3 stereocenters with complete stereocontrol. This expeditious route is unprecedented among synthetic approaches to iridoid glycosides and smoothly overcomes the hemiacetals glucosidation issue. The present inaugural total synthesis of semperoside A was achieved in 10 steps and 17% overall yield from the enantiomerically pure lactone 8, thus proving the absolute stereochemistry of 1 unequivocally.