Current Organic Chemistry - Volume 7, Issue 11, 2003

“Chiral masked forms of glyoxal” can be prepared from cheap aqueous solution of glyoxal or its simple achiral derivatives by one- or multi-step sequences involving the transformation of one or preferably both carbonyl groups, while maintaining the oxidation state of the pre-existing carbons, by reaction with chiral enantiopure compounds, such as alcohols, amines, hydrazines, 1,2-diols, 1,2-aminoalcohols and 1,2-diamines. In most cases, these chiral synthons, constituted of two equal or different functions, have been submitted to organometallic reagents. Thus, taking advantage of the auxiliary-induced asymmetric induction, optically enriched or pure 1,2- difunctional compounds have been prepared, including α-hydroxy- and α-aminoaldehydes (and the corresponding carboxylic acids by subsequent oxidation), 1,2-diols, 1,2-aminoalcohols and 1,2-diamines. On the other hand, the addition of chiral organometallic reagents to glyoxal has been seldom described. The reaction pathways, mechanisms and stereochemical models or transition states involved in the described routes are herein critically discussed.

Barbituric acid derivatives exert important action on the central nervous system, and recently have found totally new biomedicinal applications in fields such as cancer and AIDS therapy, and protease inhibitors. On the other hand, selective introduction of fluorine into biologically active compounds can either enhance their pharmacological properties or increase their therapeutic efficiency. This review focuses on the synthesis and the biological properties of fluorinated barbituric acid derivatives, which can be divided into three main categories: 1) those bearing a fluorine directly bound in position 5 of the 2,4,6-trioxohexahydro-pyrimidine ring, 2) 5-fluoroalkyl derivatives, and 3) 5-fluoroaryl derivatives.

Chiroptical methods, the circular dichroism spectroscopy (CD) in particular, appear to be sensitive, fast and convenient methods for determination of absolute configuration of chiral compounds in solution. For the CD to be applicable, however, the investigated compounds have to be not only optically active but also should absorb circularly polarized light in an accessible spectral range. To carry out the circular dichroic studies on compounds transparent in the UV-vis region, a suitable chromophoric system needs to be introduced into the molecule in the immediate vicinity of stereogenic center. In such manner the inherently transparent compounds are transformed into so-called cottonogenic derivatives. The method proposed in this work consists of the generation of chiral complexes in situ by mixing the chiral but non-absorbing substance with a solution of an achiral transition metal complex acting as auxiliary chromophore. Such complexes of general formula [M2(COOR)4]k+ X-k where M = Mo, Rh, and Ru can exchange in situ one or more of its carboxylate units with other ligands to form chiral complexes of a bridging or a chelating structure. In all cases, i.e., irrespective of the complexation mode, the CD arising within the d-d absorption bands of the metal cluster depends solely upon the chirality of the compound acting as ligand(s).A variety of biologically important compounds like e.g., amino and hydroxy acids, alcohols, amines, diols, aminols etc., are investigated as potential ligands for these studies. The examination of the CD spectra of the in situ formed chiral complexes allows assignment of the absolute configuration and conformational features of the ligands as well.

This review will attempt to cover the literatures published from 1988 dealing with cyclic and acyclic azomethine ylides in which a part or the whole of the ylide conjugation is included in a conjugated heterocycle. Special emphasis will be given to the synthetic applications of these dipoles in the synthesis of complex structures as well as in key steps of total synthesis.