Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 9, Number 18, December 2005

Contents


Editorial Pp.1801
Editorial to the Organophosphorus special issue of COC – Part I


Organophosphorus Chemistry: Therapeutic Intervention in Mechanisms of Viral and Cellular Replication Pp.1803
Nick J. Wardle, S. W. Annie Bligh & Harry R. Hudson
[Abstract]


Computer-Aided Analysis and Design of Phosphonic and Phosphinic Enzyme Inhibitors as Potential Drugs and Agrochemicals Pp.1829
¢ukasz Berlicki & Pawel Kafarski
[Abstract]


Hydrophosphination of Unactivated Alkenes, Alkynes and Allenes: A Versatile and Valuable Approach for the Synthesis of Phosphines Pp.1851
O. Delacroix & Annie-Claude Gaumont
[Abstract]


Phosphinous Acid-Boranes Pp.1883
K. Michal Pietrusiewicz & Marek Stankevic
[Abstract]


Synthesis and Coordination Chemistry of Cyanosub-stituted Phosphines Pp.1899
Irina L. Odinets, Natalya M. Vinogradova, Ekaterina V. Matveeva & Tatyana A. Mastryukova
[Abstract]




Abstracts
[Back to top]
Editorial
Editorial to the Organophosphorus special issue of COC – Part I

The Editor-in-Chief and the management of Current Organic Chemistry decided to devote a special issue to Organophosphorus Chemistry in 2005, to be followed by two more thematic issues in 2006 and 2007. The dedication of one special issue to organophosphorus chemistry, among the annual 18 issues, is a clear recognition of the importance of this subject, the recent trends and achievements of which can be surveyed at www.icpc2004.com (the website of the most recent International Conference on Phosphorus Chemistry).

The organophosphorus chemistry covered by the articles of this issue includes highlighted topics in bioorganic chemistry, organometallic chemistry, asymmetric synthesis (catalysis) supramolecular chemistry and heterocyclic chemistry.

These days the medicinal aspects of organophosphorus compounds are indeed in focus, the group of compounds with anticancer and antiviral activity forms one of the majos fields. The use of computer-aided design in the development of novel phosphonic and phosphinic acids as enzyme inhibitors, in both the agrochemical and biomedical fields, is ananother active field of research.

Phosphines are widely applied as ligands in transition metal complexes. A special and environmentally friendly method for the preparation of phosphines involves hydrophosphination. The most convenient precursors of P(III)-ligands are the corresponding boranes. The synthesis and utilisation of borane complexes of trivalent phosphorus acids is a brand new field. The coordination chemistry of cyano-substituted phosphines and heterocyclic phosphines, such as phosphinines represents a promising discipline also from the point of view of catalytic applications of transition metals. Macrocycles combined with special chelating –C(O)NHP(O)–moieties may be special complexants towards a variety of metal cations.

The P-heterocyclic field has become one of the most dynamically developing branches of organophosphorus chemistry. Thus, 5- and 6-membered P-heterocycles, as well as bridged derivatives form representative groups of ring phosphorus compounds. The newer developments of phosphole, and of dihydro- and tetrahydrophosphinine chemistry, are of interest from a number of points of view. Bridged 1,2-oxaphosphabicyclo[2.2.2]octene 2-oxides are precursors of metaphosphonates, useful in phosphonylations.

The 1. Organophosphorus Special Issue has been divided into two parts published back to back. The five reviews included in this issue (Part I) is to be followed by five other articles in Volume 10, Number 1 (Part II). The forthcoming papers are the following:

The Chemistry of Phosphinines: Syntheses, Coordination Chemistry and Catalysis
by Nicolas Mézailles and Pascal Le Floch

N-Acylamidophosphinates: Structure, Properties and Complexation Towards Main Group Metal Cations
by Felix D. Sokolov, Vasiliy V. Brusko, Nail G. Zabirov and Rafael A. Cherkasov

The Continuing Development of the Chemistry of Phospholes
by Louis D. Quin

2-Phospha- and 2,3-Oxaphosphabicyclo[2.2.2]octenes – Synthesis and Fragmentation to Low-coordinated Species
by Stefan Jankowski and Krzysztof Huben

6-Membered P-Heterocycles: 1,2-Dihydro-, 1,2,3,6-Tetrahydro- and 1,2,3,4,5,6-Hexahydrophosphinine 1-Oxides
by György Keglevich

György Keglevich
Department of Organic Chemical Technology
Budapest University of Technology and Economics
H-1521 Budapest
Hungary


[Back to top]
Organophosphorus Chemistry: Therapeutic Intervention in Mechanisms of Viral and Cellular Replication
Nick J. Wardle, S. W. Annie Bligh & Harry R. Hudson

Literature publications (up to September 2004) concerning the targeted intervention of organophosphorus synthons in mechanisms of the replicative cycle, and the therapeutic benefits resulting (of particular relevance to anticancer and antiviral therapeutics) are reviewed. DNA-cross-linking agents comprising established oxazaphosphorinanes such as cyclophosphamide, ifosfamide and trofosfamide, and the aziridine agent thiotepa are discussed along with recent developments in prodrugs of associated activated metabolites. Established and novel nucleoside phosphonates are described subsequently in relation to inhibition of viral and cellular DNA polymerases and reverse transcriptases, along with inhibition of nucleotide metabolising enzymes such as purine nucleoside phosphorylase, thymidine phosphorylase, inosine monophosphate dehydrogenase, S-adenosyl-L-homocysteine hydrolase, and ribonucleoside diphosphate reductase. In this context, the role of organophosphorus chemistry in the development of intracellular delivery systems for antiviral/anticancer nucleotides has been reviewed, as have therapeutic developments concerning the pyrophosphate mimetic foscarnet. Finally, the inhibition of virally-encoded proteases such as HIV-PR, HCMV-PR and HCV NS3/NS4A protease by substrate-mimetic organophosphorus synthons has been discussed along with the role of synthetic oligonucleotides in antisense therapies for a range of disease-states.


[Back to top]
Computer-Aided Analysis and Design of Phosphonic and Phosphinic Enzyme Inhibitors as Potential Drugs and Agrochemicals
¢ukasz Berlicki & Pawel Kafarski

A structure-based approach to design potent and selective inhibitors is an important component of the modern drug development process. As the altered activity of certain enzymes is associated with variety of pathologies, the design and synthesis of inhibitors for enzymes playing the key role in pathogenesis may result in potential therapeutic agents. Nowadays, the development of new inhibitors is often based on computer assisted design process. Although three-dimensional structure of the enzyme and mechanism of enzymatic reaction are most important for accurate design, the mode of action of already known lead compounds as well as their characteristic structural features also have to be considered.

This review summarises the current progress in computer-aided design of phosphonic and phosphinic acids and their short peptides as inhibitors of chosen enzymes of medical and agrochemical importance. Despite the mechanism of inhibitory activity two approaches for their design are presented. First one relies on the use of the crystal structure of enzymes as well as enzymes complexed with some ligands for structure-based search for novel inhibitory structures. Second enables prediction of activity of new enzyme groups of inhibitors based on the building-up relation of observed activity to specific structural features of sets of compounds of known biological activity.


[Back to top]
Hydrophosphination of Unactivated Alkenes, Alkynes and Allenes: A Versatile and Valuable Approach for the Synthesis of Phosphines
O. Delacroix & Annie-Claude Gaumont

The last years have seen many advances in the field of organometallic catalysis. Motivating much of the work has been the potential for discovering new catalytic reactions, which can be used for the synthesis of bulky chemicals and fine chemical intermediates. Since the efficiency and the selectivity of the catalyst mainly rely on the structure of the ligand, there is a great interest in the design and the synthesis of new ligands (amines, amino-alcohols, thioether, phosphines etc). From all of them, phosphine derivatives are the most widely used with transition metal catalysts. Different approaches have allowed to prepare phosphine derivatives: nucleophilic substitution of a P-chloro derivative, nucleophilic substitution using metal phosphide, C-P cross coupling etc. A greener way to phosphines is the addition of a P-H bond to a multiple bond since no atom loss is observed (atom economy concept). These reactions are mainly carried out in the presence of radical initiators or under basic conditions. Acidic and neutral media were also proposed. A few recent examples reported the use of a metal activation. This review is designed to remember some of the early aspects of hydrophosphination reactions using phosphines, protected or not, and unactivated or slightly activated alkenes, dienes and alkynes and to focus on the more promising results obtained in this field for the last 15 years. The reactions involving pentavalent phosphorus derivatives (phosphine-oxide, thiophosphines, phosphonate and phosphate derivatives etc.) are not concerned by this chapter.


[Back to top]
Phosphinous Acid-Boranes
K. Michal Pietrusiewicz & Marek Stankevic

Reactive oxygen species (ROS) such as superoxide anion radical (O2-×) play an essential role on normal cellular growth and homeostasis. However, excess ROS generated by perturbing O2-× homeostasis under various conditions of oxidative stress induce high radical toxicity, resulting in many diseases such as cancer, brain and myocardial infarction, and inflammation. Quantitative analysis of O2-× by a convenient method is a subject of intense research, since most of ROS are derived from O2-×. In situ real-time measurement of O2-× is very important to understand the relevance of ROS to many diseases. Recent progress in electrochemical sensors for the facile detection of O2-×, including biosensors utilizing a variety of metalloproteins as sensing elements for O2-× and very recently developed all-synthetic sensors with a high selectivity for O2-× detection, is reviewed. Emphasis is placed on the possibility of the all-synthetic sensor for convenient in vivo measurement of ROS.


[Back to top]
Synthesis and Coordination Chemistry of Cyanosub-stituted Phosphines
Irina L. Odinets, Natalya M. Vinogradova, Ekaterina V. Matveeva & Tatyana A. Mastryukova

Synthetic approaches to both linear and cyclic cyano-substituted phosphines (P~CN-phosphines) found an industrial application as catalyst precursors, pesticides, herbicides, flame retardants, precursors of aminophosphines etc., are reported. The main synthetic routes include reduction of P=O containing precursors, alkylation of silylphosphines and metal phosphides by halogenoalkyl(aryl)carbonitriles, phosphorylation of the latter ones, decomposition of phosphonium salts and hydrophosphination of cyano-substituted olefins proceeding under non-catalytical conditions and with use of metal complex catalysis. Merits and demerits of each approach are discussed. Phosphines bearing cyano function as an additional coordination site show diverse coordination behavior depending on the phosphine structure and nature of the metal. Four main types of complexes are observed, namely those with P-monodentate coordination, with N-monodentate coordination and complexes where bidentate coordination mode of P and N atoms is realized either at the single metal atom or of bridged type between two different metal atoms. Thus coordination behavior of such P~CN-ligands relative to transition and non-transition metals, structure features of the complexes obtained and their application in catalytic processes are discussed.