Trace metal concentrations in Mediterranean blue mussel and surface sediments and evaluation of the mussels quality and possible risks of high human consumption.

The concentrations of trace metals (Fe, Zn, Mn, Ni, Cu, Co and Cr) were determined for the first time in Mediterranean blue mussels (Mytilus galloprovincialis) and surface sediments. The mussel and sediment samples were collected from five sites on the Montenegrin coastal area (southeastern Adriatic Sea) in the fall of 2005 and 2006. The collected samples were digested with a microwave digestion system. The maximum Fe, Zn, Mn, Ni, Cu, Co and Cr mean concentrations in the mussel samples were 603.0, 345.0, 85.0, 18.9, 17.2, 9.1 and 4.2mg/kg of sample dry weight, respectively. The maximum Fe, Mn, Cr, Ni, Zn, Cu and Co concentrations in the sediment samples were 40867, 943.0, 382.0, 336.0, 67.2, 24.8 and 16.9mg/kg of sample dry weight, respectively. A correlation between the metal levels found in the mussel soft tissues with those found in sediments, for both 2005 and 2006, could be established, except for the levels of Zn observed.

Prorenin and angiotensin-dependent renal vasoconstriction in type 1 and type 2 diabetes.

Prorenin is a powerful marker for risk of nephropathy and retinopathy in diabetes, but the responsible mechanism remains unclear. Studied were 35 patients with diabetes (18 with type 1 and 17 with type 2) and 69 age-matched healthy subjects with para-aminohippurate and inulin clearances and their response to captopril. All patients with diabetes had normal renal function and no microalbuminuria. Prorenin was calculated as the difference between total renin and active renin. Active renin level in patients with diabetes (11.6 +/- 0.9 microU/ml) was significantly lower than in normal subjects (14.5 +/- 1.3 microU/ml; P < 0.05); despite this, the renal vascular response to captopril was much larger (82.9 +/- 11.5 versus 13.6 +/- 5.8 ml/min per 1.73 m(2); P < 0.01). Prorenin in both patients with type 1 and type 2 diabetes (175.7 +/- 15.1 microU/ml) also was significantly higher than in normal subjects (128 +/- 5.8 microU/ml; P < 0.01). Active renin correlated with prorenin in normal subjects (r = 0.44, P = 0.0002), and this correlation was much more striking in patients with diabetes (r = 0.72, P = 0.0001). The active renin and prorenin correlation was identical in type 1 and type 2 diabetes. There was a clear correlation between plasma prorenin and the renovascular response to captopril in patients with diabetes (P < 0.01) but not in normal subjects (P > 0.13). The strong correlation between plasma prorenin concentration and the renovascular response to captopril in diabetes supports the hypothesis of a direct effect of prorenin, but the unanticipated high degree of correlation between plasma prorenin and active renin limits the conclusions that can be drawn.

Enantioselective Diels-Alder reactions catalyzed by hydrogen bonding.

Like molecules of life (e.g., proteins and DNA), many pharmaceutical drugs are also asymmetric (chiral); they are not superimposable on their mirror images. One mirror image form (enantiomer) of a drug can have desirable activity, the other not. Consequently, the development of methods for the selective synthesis of one enantiomer is of great scientific and economic importance. We report here that a simple, commercially available chiral alcohol, alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL), catalyzes the all-carbon Diels-Alder reactions of aminosiloxydienes and substituted acroleins to afford the products in good yields and high enantioselectivities (up to 92% enantiomeric excess). It is remarkable that the reactions are promoted by hydrogen bonding, the ubiquitous "glue" that helps to keep water molecules together and holds up the 3D structures of proteins. Hydrogen bond catalysis is little used in chemical synthesis, wherein most reactions are promoted by complexes of Lewis acidic metal salts coordinated to chiral ligands. As it does for enzymes, hydrogen bonding not only organizes TADDOL into a well defined conformation, but, functioning as a Brønsted acid catalyst, it also activates the dienophile toward reaction with the diene. The gross structure of the TADDOL has been found to have a profound influence on both the rate and the enantioselectivity of the cycloadditions. These structure-function effects are rationalized by evaluating the conformation adopted by the TADDOLs in the crystal state. It is suggested that pi,pi-stacking plays an central role in the overall catalytic cycle, in particular, the enantioselective step.

A general strategy to elisabethane diterpenes: stereocontrolled synthesis of elisapterosin B via oxidative cyclization of an elisabethin precursor.

Described is an efficient synthesis of the complex bioactive natural product, elisapterosin B, a potent in vitro inhibitor of Mycobacterium tuberculosis H37Rb. The synthesis elisapterosin B, prepared in its enantiomeric form, proceeds by a highly stereocontrolled sequence commencing with a simple glutamic acid derived compound. Pivotal steps in the sequence include (a) a pinacol-type ketal rearrangement to transfer chirality, (b) an IMDA reaction of an E,Z-diene to construct the elisabethin skeleton, and (c) a biosynthesis-inspired oxidative cyclization of the elisabethin precursor to elisapterosin B.