Colin Eldred

An efficient method for the synthesis of N,N′-dimethyl-1,2-diamines

Abstract A simple method for the preparation of N,N′-dimethyl-1,2-diamines is described. The method requires the dimethylation of a diazaphospholidine oxide followed by acid-catalysed hydrolysis.

Fibrinogen receptor antagonists : Design and clinical applications

Publisher Summary This chapter discusses the design and clinical applications of fibrinogen receptor antagonists. The concept of a fibrinogen receptor antagonist as a powerful new antithrombotic mechanism arose from consideration of the central role of the platelet in thrombosis. In healthy blood vessels, “resting” platelets do not adhere to the nonthrombogenic surface of intact endothelium. However, platelets can adhere to subendothelial structures of a damaged vessel wall, for example, following rupture of an atherosclerotic plaque, resulting in initiation of the process of clot formation. The fibrinogen receptor represents the best characterized member of the integrin family of cell adhesion receptors, which are involved in a wide variety of cell–cell and cell-extracellular matrix interactions. The pharmacodynamic duration of action of fibrinogen antagonists has generally been assessed by measuring inhibition of platelet aggregation ex vivo in samples of blood taken at intervals following i.v. or p.o. administration of drug, for example in the marmoset. The most common approach used to increase bioavailability of fibrinogen antagonists is to mask one or both of the charged entities thereby increasing log D and increasing the likelihood of absorption through lipophilic membranes. In addition to studying the ability of fibrinogen antagonists to prevent thrombus formation, the ability of these agents to enhance the outcome of thrombolytic therapy has been studied in several animal models, in which thrombolysis alone is only partially effective and/or is followed by rapid reocclusion.

Synthesis and applications to asymmetric catalysis of a series of mono- and bis(diazaphospholidine) ligands

The synthesis of a series of closely related mono- and bis(diazaphospholidine) ligands has been achieved using the condensation of a diamine with a bis(dimethylamino)arylphosphine. The resulting ligands have given excellent results in palladium-catalysed allylic substitution reactions to form C–C bonds (up to 89% ee) and C–N bonds (up to 78% ee).

Design, synthesis and preliminary studies on a novel class of chiral receptor for the recognition of amino acid derivatives1

The design and synthesis of a novel class of chiral receptor for the recognition of amino acid derivatives is described. Moderate enantioselectivity is observed in binding experiments.

Synthesis and applications of a new class of phosphorus donorligands for asymmetric catalysis

The synthesis and applications to allylic substitutions of a range of novel ligands based on diazaphospholidines is described; enantiomeric excesses of up to 89% were achieved in an allylic substitution reaction.