Dolores Molero

Identification of a urine metabolomic signature in patients with advanced-stage chronic kidney disease

The prevalence of chronic kidney disease (CKD) is increasing and frequently progresses to end-stage renal disease. There is an urgent demand to discover novel markers of disease that allow monitoring disease progression and, eventually, response to treatment. To identify such markers, and as a proof of principle, we determined if a metabolite signature corresponding to CKD can be found in urine. In the discovery stage, we analyzed the urine metabolome by NMR of 15 patients with CKD and compared that with the metabolome of 15 healthy individuals and found a classification pattern clearly indicative of CKD. A validation cohort of urine samples from an additional 16 patients with CKD and 15 controls was then analyzed by (Selected Reaction Monitoring) liquid chromatography-triple quadrupole mass spectrometry and indicated that a group of seven urinary metabolites differed between CKD and non-CKD urine samples. This profile consisted of 5-oxoproline, glutamate, guanidoacetate, α-phenylacetylglutamine, taurine, citrate, and trimethylamine N-oxide. Thus, we identified a panel of urine metabolites differentially present in urine that may help identify and monitor patients with CKD.

2D Ultrafast HMBC: A Valuable Tool for Monitoring Organic Reactions§

Ultrafast 2D HMBC spectroscopy permits real-time monitoring of a reaction based on the structural changes produced in a carbonyl carbon atom. This new technique was used to study the reaction of ketones, nitriles, and Tf(2)O, affording relevant information about new intermediates and kinetic data.

Diastereoselective Synthesis of C60/Steroid Conjugates

The design and synthesis of fullerene-steroid hybrids by using Pratos protocol has afforded new fullerene derivatives endowed with epiandrosterone, an important naturally occurring steroid hormone. Since the formation of the pyrrolidine ring resulting from the 1,3-dipolar cyloaddition reaction takes place with generation of a new stereogenic center on the C2 of the five-membered ring, the reaction proceeds with formation of a diastereomeric mixture [compounds 6 and 7 in 70:30 ratio, 8 and 9 in 26:74 ratio (HPLC)] in which the formation of the major diasteroisomers 6 and 9 is consistent with an electrophilic attack of [60]fullerene on the Re face of the azomethine ylide directed by the steroidic unit. The chiroptical properties of these conjugates reveal typical Cotton effects in CD spectra that have been used to assign the absolute configuration of the new fulleropyrrolidines. The electrochemical study of the new compounds reveals the presence of four quasi-reversible reduction waves which are cathodically shifted in comparison with the parent C60, thus ascertaining the proposed structures.

One-Pot Synthesis of 1,3,5-Triazine Derivatives via Controlled Cross-Cyclotrimerization of Nitriles: A Mechanism Approach

The reaction of equimolecular amounts of a nitrile and triflic anhydride or triflic acid at low temperature produces an intermediate nitrilium salt that subsequently reacts with 2 equiv of a different nitrile at higher temperature to form 2,4-disusbstituted-6-substituted 1,3,5-triazines in moderate to good yields. This synthetic procedure has also been applied to the preparation of a 1,3,5-triazine having three different substituents. The results are explained in terms of a mechanism based on the relative stability of the intermediate nitrilium salts that are formed through a reversible pathway. The formation of a substituted isoquinoline using benzyl cyanide as the second nitrile supports the postulated mechanism as well as the structure of derivatives of the proposed intermediate when the reaction is carried out in the presence of different nucleophiles other than nitriles. Theoretical calculations and the monitoring of the reaction using (1)H and (13)C NMR spectroscopy are in agreement with the proposed mechanism pathway.

1H and 13C spectral assignment of 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes

1H and 13C NMR spectroscopic data for 1,4,5,6,7,8‐hexahydroquinolines and their oxa‐analogues, 5,6,7,8‐tetrahydro‐4H‐chromenes, were fully assigned by combination of one‐and two‐dimensional experiments (DEPT, HMBC, HMQC). Both heterocyclic systems show similar spectroscopic properties with some remarkable differences. Copyright

Synthesis and structural study of new highly lipophilic 1,4-dihydropyridines

A new series of 1,4-dihydropyridines (1,4-DHPs) endowed with ester groups bearing long and functionalised alkoxy chains at the C3 and C5 positions of the nitrogen ring have been prepared from the corresponding β-keto esters which were in turn prepared by a lipase catalysed transesterification reaction. The structural study has been carried out by X-ray crystallography and theoretical calculations at the semiempirical (AM1), ab initio (HF/6-31G*) and B3LYP/6-31G* levels and reveals that the long alkyl chains do not have any influence on the required geometry of the 1,4-DHPs for biological activity. However, these chains have a strong impact on the lipophilicity and, therefore, they could be used to gain a better control of the duration of the pharmacological action.

Catalytic Stereodivergent Synthesis of Steroid–Fulleropyrrolidine Hybrids

The diastereoselective synthesis of cis and trans steroid-fulleropyrrolidines hybrids by reaction of N-metalated azomethine ylides [Cu(II) or Ag(I)] with the appropriate chiral ligand and C60 is described. The experimental findings reveal that the azomethine ylide stabilized by an allylic group cycloadds to [60]fullerene in an efficient manner and with a good diastereomeric excess. Furthermore, the new generated stereocenters are fully controlled by the catalytic systems used without being influenced by the chirality of the steroid. Interestingly, by this synthetic methodology the each one of the four possible stereoisomers have efficiently been obtained and characterized by CD spectra.