Current Organic Chemistry - Volume 6, Issue 15, 2002

Desymmetrisation processes allow a rapid and stereocontrolled elaboration of readily available σ- symmetric precursors. Since it is often more convenient to prepare symmetrical compounds, breaking the symmetry at a well-defined point in a synthesis may constitute a powerful manner to introduce several chiral centres with high level of diastereo- and enantiocontrol.This review is intended to provide the reader with a timely report on the novel synthetic possibilities offered by desymmetrisation of some substituted 1,3-cyclopentadienes and 1,4-cyclohexadienes. Our recent investigations in this field, mainly on silicon derived cyclopenta- and cyclohexadienes will be described along with reports by other groups working on closely related precursors. The scope and limitation of this methodology will be examined. The influence of the ring substituents on the regio- and stereochemical outcome of the desymmetrisation processes will also be discussed. For instance, we have demonstrated that a silicon group at the pseudo-symmetrical position, was crucial for the control of the diastereofacial selectivity. The discussion will also focus on the asymmetric processes which have been used to break the symmetry of the dienes and on the elaboration of the adducts to construct biologically relevant targets. Sharpless asymmetric dihydroxylation and amino-hydroxylation, hydroboration and cyclopropanation are the most reliable and efficient processes, which have been used so far. Asymmetric Heck reaction has also been employed demonstrating that this methodology can be further enriched with new asymmetric processes and that numerous homochiral intermediates would be at hand in a near future. Finally, illustration of the viability of such a strategy will be provided along with the total synthesis of relevant classes of natural products such as cyclitols, sugar mimics having glycosidase inhibitory activities, alkaloids and sesquiterpenes.

Cis-trans isomerization of amide bonds plays a crucial role in protein structure as well as in the activity of peptides. In particular, the amino acyl-proline cis-trans interconversion is one of the limiting steps of protein folding and is accelerated by a family of proteins called immunophilins or peptidyl-prolyl isomerases (PPIases). Consequently, PPIases are implicated in many biological processes such as protein expression, mitosis and cellular communication. They also play a role in immunosuppression as well as in several pathologies such as AIDS and severe neurodegenerative disorders. Therefore, immunophilins are attractive targets for the design of novel therapeutics. In this review, the design of selective PPIases inhibitors will be detailed on the basis of structural data and structure-activity realtionship studies. The preparation and biochemical evaluation of new molecules derived from immunosuppressive inhibitors of immunophilins such as cyclosporin and FK506 will be tackled. Results, collated with structural data, will then be used with view to developing potent and selective inhibitors devoid of immunosuppressive activity. In particular the design and synthesis of ground-state inhibitors and non-isomerisable analogs of the amino acyl-proline moiety, including constrained proline, proline mimetics and endogenous cyclophilin ligands, will be explained. Finally, we will focus on the synthesis of transition-state analog inhibitors of the PPIases including ketoamides, phosphonamides and sulfonamides.

The biomimetic phenolic and non-phenolic oxidative coupling approach to the construction of biaryl connections represents an alternative to other known methodologies, such as Ullmann or Stille reactions, with the advantage that no functionalization at the coupling positions is required. However, most of the reagents commonly used for oxidative bond formation are highly toxic and environmentally harmful.This review focuses on the use of easily handle and less toxic hypervalent iodine reagents phenyliodine(III)bis(trifluoroacetate) or PIFA and phenyliodine(III)diacetate or PIDA, to perform such a key transformation as the formation of the biaryl linkage is in Synthetic Organic Chemistry. This methodology has been used in the synthesis of symmetric and unsymmetric biaryl compounds in both inter- and intramolecular fashion with high yields and complete regioselectivity. Moreover, chiral biaryl derivatives have been successfully synthesized employing these reagents.On the other hand, recent results have demonstrated that a combination of the advantages shown by this type of reagents, with those derived from solid phase organic synthesis can be successfully applied to improve the construction of derivatives incorporating the biaryl framework.Finally, this methodology had not been applied to perform the synthesis of aryl-heteroaryl bonds so far. This review also summarizes our recent advances toward this end.

Several series of polyammonium and polyphosphonium organic salts are surveyed. These polycationic salts may be divided into several topographical categories based upon their structural characteristics (such as dendrimers, rings and strings) and their physical state (solid, liquid crystalline, liquid). The synthetic approaches and the physical / chemical characteristics for each series are surveyed, along with their physical and chemical characteristics, including their utility for ion exchange, their interaction with biological systems, and their antihydrophobic effect.

The design and construction of optically active molecules comprised of a chiral heteroatom center is a rapidly developing research field. This review focuses on the recent development in the synthesis of such molecules which possess a chiral heteroatom center of the group 13-16 metal elements, that is, boron, silicon, germanium, tin, arsenic, antimony, bismuth, selenium and tellurium.