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Although GPC has long been recognized as a degradation product of phosphatidylcholine, only recently is there wide appreciation of its role as a compatible and counteracting osmolyte that protects cells from osmotic stress. GPC is osmotically regulated in renal cells. Its level varies directly with extracellular osmolality. Cells in the kidney medulla in vivo and in renal epithelial cell cultures (MDCK) accumulate large amounts of GPC when exposed to high concentrations of NaCI and urea. Osmotic regulation of GPC requires choline in the medium, presumably as a precursor for synthesis of GPC. Choline transport into the cells, however, is not osmoregulated. The purpose of the present studies was to use MDCK cell cultures as a defined model to distin h whether osmotically induced accumulation of GPC results from increased GPC synthesis or decreased GPC disappearance. The rate of incorporation of 14C from [14C]choline into GPC, the steady-state GPC synthesis rate, and the activity ofphospholipase A2 (which can catalyze a step in the synthesis of GPC from phosphatidylcholine) are not increased by high NaCl and urea. In fact all are decreased by approximately one-third. Therefore, we find no evidence that high NaCI and urea increases the GPC synthesis rate. On the other hand, the rate coefficient for cellular GPC disappearance and the activity of GPC:choline phosphodiesterase (EC 3.1.4.2), which catalyzes degradation of GPC, are decreased by approximately two-thirds by high NaCl and urea. We conclude that high NaCl and urea increase the level of GPC by inhibiting its enzymatic degradation.Cells in the renal medullas of mammals contain large amounts of organic osmolytes [namely, GPC (1, 2), sorbitol, inositol, and glycine betaine (for review, see ref.3)]. When renal medullary osmolality rises (as, for example, during antidiuresis), the concentration of these organic osmolytes in medullary cells increases slowly over several days (4). The renal medullary organic osmolytes accumulate in response to the high extracellular concentrations of NaCl and urea in this region of kidney and vary with the NaCl and urea concentrations. The organic osmolytes help balance the high osmotic pressure of the extracellular NaCl. The utilization of these compounds, rather than inorganic salts, for this purpose is attributed to the organic osmolytes being compatible solutes (5, 6) that can accumulate to high levels in cells without perturbing intracellular macromolecules, whereas high concentrations of inorganic ions are perturbing. GPC is thought also to be a counteracting solute (5-7) that protects intracellular macromolecules from being denatured by the high concentration of urea in the renal medulla.

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Enantioselective catalytic reactions that operate directly on inexpensive unactivated alkenes are extraordinarily useful for the preparation of chiral organic building blocks and new materials. While a number of such processes have been developed, our ability to meet the intensifying demand for inexpensive stereochemically complex materials will require a significant expansion of practical catalytic asymmetric reaction methodology. In this regard, the rhodium-catalyzed enantioselective diboration reaction has been developed in order to address a number of extant problems in catalytic alkene transformation simultaneously. This process provides an enantiomerically enriched reactive dimetalated intermediate which can be converted to a variety of difunctional reaction products.

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Compound 1, a potent and irreversible inhibitor of β-lactamases, is in clinical trials with β-lactam antibiotics for the treatment of serious and antibiotic-resistant bacterial infections. A short, scalable, and cost-effective route for the production of this densely functionalized polycyclic molecule is described.