Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 11, Number 11, July 2007

Contents

Synthetic Organic Chemistry
Guest Editor: Antonino Corsaro


Editorial Pp. 958


Synthesis and Synthetic Applications of 1,2,4-Oxadiazole-4 Oxides Pp. 959-986
Paolo Quadrelli and Pierluigi Caramella
[Abstract]


Versatile Use of Carbon Dioxide in Synthesis of Organic Carbamates Pp. 987-998
Devdutt Chaturvedi and Suprabhat Ray
[Abstract]


Chiral Synthesis of Carbocyclic Nucleoside Analogs from Non carbohydrate Precursors Pp. 999-1016
Fabio Casu, Maria Assunta Chiacchio, Roberto Romeo and Giuseppe Gumina
[Abstract]


Chiral Synthesis of Heterosubstituted Nucleoside Analogs from Non-carbohydrate Precursors Pp. 1017-1032
Fabio Casu, Maria Assunta Chiacchio, Roberto Romeo and Giuseppe Gumina
[Abstract]




Abstracts

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Editorial

The first part of a special issue on "Synthetic Organic Chemistry", with which I have initiated my activity of Guest Editor, is inserted in this Volume 11, Number 11, July 2007 of Current Organic Chemistry. It has indeed been a great pleasure to be associated with this venture that allows to introduce me to the various colleagues for the first time. Certainly, since I have got an engagement for the next two years, this my new activity will be improved in the future; in particular, it will aim at shortening publication times of reviews.

In this publication four reviews are reported that brings the readers to the field of heterocycles syntheses and utilization of carbon dioxide in the synthesis of organic carbammates.

The first thick review, written by Paolo Quadrelli and Pierluigi Caramella from the University of Pavia (Italy) is comprehensive of the synthesis and synthetic applications of the 1,2,4-oxadiazole-4-oxides which have never been made before.

In the initial part of the review, including 52 references, the aim of Authors is to account the state of the art in the synthesis of 1,2,4-oxadiazole-4-oxides, starting from the very first approaches up to the most recent methods, which is discussed in details. They highlight as 1,2,4-Oxadiazole-4-oxides are a family of heterocycles closely related to the chemistry of nitrile oxides which were actively studied in the past half century and provided the basic knowledge on 1,2,4-oxadiazole-4-oxides.

The final part of the review, including 35 references, will be dedicated to the chemical behaviour of 1,2,4-oxadiazole-4-oxides, mainly concerning their chemical stability and their use as precursors of reactive species, even coupled with new synthetic methodologies. Their chemistry is related to the fragility of their heterocyclic ring, which undergoes thermal or photochemical cycloreversion to nitriles and nitrosocarbonyl intermediates. Trapping of nitrosocarbonyls takes place easily with dienes and enes, affording a variety of hetero Diels-Alder and ene adducts, which attract great interest because of their useful synthetic elaboration toward many natural products of potential pharmaceutical applications. The photochemical cleavage have been applied successfully to solid phase chemistry, allowing for a safe and environmental friendly methodology for the synthesis of important intermediates.

Devdutt Chaturvedi and Suprabhat Ray from Medicinal and Process Chemistry Division of Indian Central Drug Research Institute contributed to the second review, which deals with the synthesis of organic carbamates extensively based on the utilization of carbon dioxide as a cheap and harmless reagent in alternative to harmful and toxic, but classically used, reagents like phosgene, and its derivatives or carbon monoxide.

The review summarizes the preparations of organic carbamates starting from carbon dioxide in the gaseous state affording low yields, but, however, it reportes that yields can be enhanced by using basic catalysts. Good yields of carbamates can be obtained also by supercritical carbon dioxide in the presence of basic and phase transfer systems which act as catalysts. Alternatively, good yields can be achieved also by means of electrochemical processes where the base is electrochemically generated from pyrrolidone, associated with tetraethylammonium cation in the presence of amines, followed by the addition of carbon dioxide and ethyl iodide. The review, including 73 references, comes to an end discussing a comparison of carbamate synthetic methods through the employment of organic carbonates and that one of carbon dioxide.

The last two reviews provided by Giuseppe Gumina and Fabio Casu of the Medical University of South Carolina and his co-aouthors Maria Assunta Chiacchio of the Catania Univesity and Roberto Romeo of Messina University discuss chyral syntheses of carbocyclic and heterosubstituted nucleoside analogs from non-carbohydrate precursors.

Among the many classes of nucleoside analogs that have been prepared and evaluated, carbocyclic and heterosubstituted nucleoside analogs represent a very important group of molecules, both chemically and biologically. Authors surveys all their syntheses which were elegantly and efficiently achieved from non-carbohydrate starting materials, either from natural optically active molecules, via chemical or enzymatic desymmetrization of prochiral molecules, or resolution of racemates. Of these two reviews, the first one, including 82 references, takes into account carbocyclic nucleoside analogs which are subdivided into three chapters concerning cyclopentyl, cyclobutyl and cyclopropyl nucleoside analogs, the preparation of which has required a number of different strategies. The second one, including 48 references, surveys oxathiolanyl, dioxolanyl, and isoxazolidinyl nucleoside analogs, which are synthetized, at any rate, from chiral starting materials, and enzymatic or chemical resolution of a racemic intermediate. For the synthesis of isoxazolidinyl nucleosides, 1,3-dipolar cycloaddition has been a favorite approach, and the necessity to obtain optically active molecules has been addressed by asymmetric induction using chiral dipoles or dipolarophiles.


Antonino Corsaro
Department of Chemical Science
University of Catania
Italy


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Synthesis and Synthetic Applications of 1,2,4-Oxadiazole-4 Oxides
Paolo Quadrelli and Pierluigi Caramella

The first 1,2,4-oxadiazole-4-oxide was prepared by Wieland a century ago, but this compound remained largely a chemical curiosity until very recently. 1,2,4-Oxadiazole-4-oxides are a family of heterocycles closely related to the chemistry of nitrile oxides which were actively studied in the past half century and provided the basic knowledge on 1,2,4-oxadiazole-4-oxides. The dimerizations of nitrile oxides under acidic or basic conditions were thoroughly studied by different research groups, and offer the more common entries to the symmetrical substituted 1,2,4-oxadiazole-4-oxides. A more general route to symmetrical and unsymmetrical substituted 1,2,4-oxadiazole-4-oxides is based on the nitrile oxide cycloadditions to amidoximes. A variety of other 1,2,4-oxadiazole-4-oxides forming reactions are also known in the literature. Many of these reactions were neither fully exploited nor mechanistically understood since they require unusual starting reagents, often difficult to prepare, or take place affording complex mixtures of products. Some of these methods still await for improved procedures and proper mechanistic attention to be of general use and will be reviewed shortly.

The chemistry of 1,2,4-oxadiazole-4-oxides is related to the fragility of the heterocyclic ring, which undergoes thermal or photochemical cycloreversion to nitriles and nitrosocarbonyl intermediates. Trapping of the nitrosocarbonyls takes place easily with dienes and enes, affording a variety of hetero Diels-Alder and ene adducts, which attract great interest because of their useful synthetic elaboration toward many natural products of potential pharmaceutical applications.

The high efficiency of the photochemical cleavage of 1,2,4-oxadiazole-4-oxides at room temperature or well below affords the softest entry to the nitrosocarbonyls and allows for the study of their chemistry under convenient and simple experimental conditions. The photochemical cleavage have been applied successfully to Solid Phase chemistry, allowing for a safe and environmental friendly methodology for the synthesis of important intermediates.

This report is comprehensive of the synthesis and synthetic applications of the 1,2,4-oxadiazole-4-oxides.


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Versatile Use of Carbon Dioxide in Synthesis of Organic Carbamates
Devdutt Chaturvedi and Suprabhat Ray

Organic carbamates classically have been synthesized starting from amines using harmful and toxic reagents, like phosgene or its derivatives, and carbon monoxide. Recently, carbon dioxide was used as a cheap and harmless reagent for the synthesis of organic carbamates in the gaseous or supercritical state, or in an electrochemical process as an alternative to the harmful and toxic reagents. The present review will deal with the extensive use of carbon dioxide in the synthesis of organic carbamates.


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Chiral Synthesis of Carbocyclic Nucleoside Analogs from Non carbohydrate Precursors
Fabio Casu, Maria Assunta Chiacchio, Roberto Romeo and Giuseppe Gumina

Nucleosides represent a very important group of molecules, both chemically and biologically. Over the past forty years, the continued success of nucleoside analogs as chemotherapeutic agents has been both the result of and the driving force for the development of new synthetic methodologies to access analogs that may differ considerably from natural nucleosides. Among the many classes of nucleoside analogs that have been prepared and evaluated, carbocyclic nucleosides featured diverse and challenging syntheses and interesting biological activity. Carbohydrate chemistry has been elegantly and thoroughly exploited for the synthesis of carbocyclic nucleoside analogs, thanks to the availability and versatility of highly functionalized chiral precursors. In a number of examples, however, the synthesis of carbocyclic nucleosides has been elegantly and efficiently achieved from non-carbohydrate starting materials, either from natural optically active molecules, via chemical or enzymatic desymmetrization of prochiral molecules, or resolution of racemates. This review will discuss chiral syntheses of carbocyclic nucleoside analogs from non-carbohydrate precursors.


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Chiral Synthesis of Heterosubstituted Nucleoside Analogs from Non-carbohydrate Precursors
Fabio Casu, Maria Assunta Chiacchio, Roberto Romeo and Giuseppe Gumina

The discovery of the potent antiviral activity of oxathiolanyl and dioxolanyl nucleosides prompted the extensive exploration of the chemistry and biology of heterosubstituted nucleoside analogs, in which the sugar moiety is replaced by a diheterocyclic ring. Carbohydrate-based synthetic approaches allowed the stereoselective synthesis of enantiomerically pure D- and L-analogs. However, due to the chemical nature of these molecules, approaches based on non-chiral starting materials and including chemical or enzymatic resolution steps proved advantageous for large scale syntheses. For the synthesis of isoxazolidinyl nucleosides, 1,3-dipolar cycloaddition has been a favorite approach, and the necessity to obtain optically active molecules has been addressed by asymmetric induction using chiral dipoles or dipolarophiles. This review will summarize the most interesting syntheses of heterosubstituted nucleoside analogs from non-carbohydrate precursors.