Current Organic Chemistry - Volume 14, Issue 5, 2010

After the publication of Organophosphorus (OP) special issues 1-6 of Current Organic Chemistry in recent years, this series may perhaps be regarded to be traditional. As the next step, the 7. OP special issue is announced here. Organophosphorus chemistry hides a lot of exciting fields in itself, such as syntheses, theoretical aspects, bioactivity and a broad spectrum of applicability. In this issue two articles are connected to the field of biologically active organophosphorus compounds. The first one explores the synthesis and therapeutic role of O-phosphotyrosine analogues, while the second one is on the synthesis and antidotal effects of pyridinium aldoximes used in the treatment of acetylcholine esterase organophosphate contamination. The next three papers comprises synthetic organic chemistry. Possible syntheses of alkenylphosphines that are useful building-blocks in the preparation of a variety of organophosphorus compounds are discussed. Heterocyclic chemistry is represented by tri- and pentavalent amidoesters and diamides that incorporate stereogenic phosphorus atom. Phosphorus dendrimers as such, express the presence of arts in organophosphorus chemistry. The species introduced are not only wonderful, but also can be used as sensors in analytical chemistry.

The development of O-phosphotyrosine (pTyr) analogues is reviewed, along with their application in peptidomimetic ligands to proteins implicated in disease-states arising from dysfunctional intracellular signal transduction pathways. Salient features of chemical syntheses are critiqued, including those of established mimetics such as 4'-(phosphonomethyl)phenylalanine (Pmp), 4'- (phosphono)phenylalanine (Ppp) and 4'-(phosphonodifluoromethyl)phenylalanine (F2Pmp), their respective (α-methyl)phenylalanine analogues and “preorganised” side-chain cyclised pTyr mimetics. Syntheses of 4'-(phosphinomethyl)phenylalanines are also described, as are “bone-directing” residues such as 4'-(diphosphonomethyl)phenylalanine (dpmF), 3',4'-(diphosphono)phenylalanine and 4'- carboxymethyloxy-3'-(phosphono)phenylalanine (CPP), capable of eliciting additional interactions with pTyr-binding subsites of specified proteins. The utility of [(4'-phosphonomethyl)phenyl]propenoic acid in current developments is also discussed as a route to a range of α- and β-substituted pTyr mimetics, and to pTyr mimetics bearing the requisite β-vinyl functionality to facilitate macrocyclisation via olefin metathesis - of interest in the development of structures exhibiting global conformational constraint. Finally, developments in prodrug presentation of pTyr mimetics are also discussed.

Pyridinium aldoximes are used as antidotes in organophosphate poisoning. In the reactivation process they form a complex with the organophosphates, even if the serine active site of acetylcholinesterase enzymes has been inactivated by the organophosphorus compounds. Essential disadvantage of the previously used pyridinium aldoximes is the instability and the toxicity of these complexes. Novel pyridinium aldoximes show more effective detoxifying effects. A general scheme of the synthesis of several novel and very promising pyridinium aldoximes and their basic characteristics are shown in this paper.

Alkenylphosphines are compounds of great interest in view of their structures. Hence, these phosphorus derivatives bear a carbon- carbon double bond, directly linked to the phosphorus atom. This insaturation may be used as a coordinating part in presence of a metal or as a reactive part in contact with an electrophile. Thus, alkenylphosphines have found numerous applications in various fields of chemistry. They are useful intermediates in organic synthesis, as precursors of polyphosphines or dendrimers, or as dienophiles in cycloaddition reactions. Due to the presence of both the phosphorus atom and the carbon-carbon double bond, they are of great interest in coordination chemistry. Recently, they were also used as ligand in homogeneous catalysis. Alkenylphosphines are mainly prepared by reaction between halophosphines and alkenyl organometallic species, by hydrophosphination of alkynes or by C-P cross-coupling reactions. The aim of this review will be to describe these methods, emphasizing particularly on the catalytic ones. The new methodologies involving the functionalization of alkynylphosphines and the bis-functionalization of alkynes, which recently appeared in the literature will also be documented. Less commonly used reactions such as alkylation of primary or secondary vinylphosphines, reduction of phosphine-oxides or phosphinates will be briefly reported.

This review presents the use of cyclic tri- and pentavalent amidoesters and diamides with a stereogenic phosphorus as chiral stoichiometric auxiliaries in asymmetric synthesis. It shows that these compounds are especially useful for the preparation of selected acyclic enantiomerically (diastereomerically) pure (or enriched) tricoordinated-trivalent and tetracoordinated-pentavalent derivatives and as precursors of stereogenic phosphorus-containing carbanions. Their utility in a few other asymmetric reactions is also discussed.

Dendrimers are a very special type of hyperbranched polymers, synthesized step by step from a central core, by the repetition of a sequence of reactions. Phosphorus-containing dendrimers, that are dendrimers possessing one phosphorus atom at each branching point, possess numerous properties, most generally due to the presence of multiple functional groups in close proximity, which may induce cooperative effects. Such effect is in particular highly desirable when creating sensors. Indeed, in order to comply with environmental friendly criteria, a sensor must be sensitive, specific, and reusable. The use of phosphorus-containing dendrimers for creating sensors may afford such properties. This review is divided in 4 main headings. The first one concerns the self-diagnosis of the dendritic structure, purity, size and properties; the second one describes the use of these dendrimers as chemical sensors; the third one emphasizes the role of dendrimers for the elaboration of biological sensing devices; and finally the fourth one describes the use of fluorescent dendrimers for biological imaging. Several of these properties are due to the presence of phosphorus at all branching point of these structures.