Current Organic Chemistry - Volume 8, Issue 13, 2004

Conduritols are 1,2,3,4-cyclohexenetetrol isomers and exist in ten possible isomeric forms (two mesofour DL-pairs) and have been labelled A, B, C, D, E and F. All of the possible conduritol isomers have already been synthesised starting from completely different materials and their biological importance studied. Transformation of the aromatic compounds into diols has opened up a new synthetic approach to the various conduritol isomers and their derivatives. Conduritols are useful precursors in the preparation of cyclitols such as myo-inositols phosphates and pseudo-sugars, some of which are important mediators in many cellular processes. Conduritol epoxides and aminoconduritols act as inhibitors of glycosidases, cyclophellitols have proven to be potent inhibitors of human immunodeficiency virus (HIV) and glycosidases and conduritol-A analogues modulate the release of insulin. This review is not intended to be exhaustive and is aimed at highlighting the progress in the synthesis of conduritols and their derivatives, as well as their synthetic applications and biological importance mainly in the last decade.

Synthesis of C-glycosides, C-linked saccharides and new glycosubstances has been the subject of considerable interest in carbohydrate, enzymatic and metabolic chemistry, since some of such compounds exhibit exciting biological properties. As a consequence, the design and implementation of stereo selective strategies for preparing bio-active carbohydrates became a prominent issue. This article is mainly aimed at the presentation of the research findings of our group on the synthesis of C-alkyl and C-aryl glycosides, higher sugars; ‘de novo’ construction of disaccharides from furanyl and propargyl sugars; [3+3] annulation routes to carbocycles and pseudo saccharides; 1,3-dipolar cycloaddition to isoxazolidine sugars and saccharides; radical routes to spiro acetal saccharides and ulosonic acid derivatives.

Polyhydroxylated alkaloids are frequently found in living systems. More than hundred compounds have been isolated from plants and microorganisms. Besides their utility as powerful tools in fundamental studies of the catalytic mechanism of glycosidases and glycosyltransferases, many natural polyhydroxylated alkaloids represent potential therapeutic agents. Due to the fact that very few compounds are commercially available a tremendous effort has been made to establish valuable synthetic approaches. This report which is not intended to be exhaustive is aimed at highlighting the progress in the synthetic methods that have appeared in the literature the last seven years concerning elaboration of natural polyhydroxylated pyrrolidines, piperidines, pyrrolizidines and indolizidines.

The synthesis of racemic 2-(4-{[4-(quinolin-2-ylmethoxy)phenyl]sulfanyl} phenyl)propionic acid (VUFB 20615) and preparation of 2-methyl-2-(4-{[4-(quinolin-2-ylmethoxy)phenyl]sulfanyl}phenyl)propionic acid (VUFB 20623) as new potential antileukotrienic drugs are described. Due to a low reactivity of the 4-substituted aryl bromides (coupling of the 4-substituted aryl bromides do not provide an activating functional group with 4- methoxybenzene-1-thiol), special conditions, in particular specific heterogeneous copper catalysts, were used. Various methods of 2-substituted propionic acid preparation have been discussed in the paper. In vitro cytotoxicity testing was performed using a microplate colorimetric acid phosphatase assay. Antiplatelet activity was evaluated using in vitro test in human platelet-rich plasma.

β-Oxophosphoranes / ylides, versatile intermediates in synthetic organic chemistry can be prepared by the novel reaction of P-aryl cyclic phosphine oxides, such as 2,3-dihydro- and 2,3,4,5-tetrahydro-1H-phosphole 1- oxides, as well as 1,2-dihydrophosphinine 1-oxides with dialkyl acetylenedicarboxylates (DAAD). The reaction involves a spirocyclic oxaphosphete intermediate formed by the (2+2) cycloaddition of the P=O bond and the acetylene moiety and follows an inverse Wittig protocol that was evaluated by PM3 and Hartree-Fock ab initio quantum chemical calculations. The interaction of iminophosphine derivatives of the Martin ligand with acetylenic diacid esters follows a similar reaction path affording β-iminophosphoranes / ylides. In these cases, the azaphosphete is an intermediate, or one component of an equilibrium system. Another synthetic method for β- oxophosphoranes / ylides comprises the acylation of stabilised phosphonium ylides in position α. Under flash vacuum pyrolytic conditions, the b-oxophosphoranes / ylides are fragmented to the mixture of the corresponding acetylene and phosphine oxide. This reaction path is exactly the opposite of the formation of b-oxophosphoranes from a phosphine oxide and acetylene derivative that was mentioned above. Some other reactions of heterocyclic b- oxophosphoranes / ylides, such as reduction, deacylation and alkoholysis are also discussed that lead to valuable families of compound.

Magnesium in methanol(Mg / MeOH) system is an extremely versatile, efficient, economical and convenient reducing agent for various reactions useful for organic synthesis such as reductive cyclization, reductive elimination, reductive cleavage, reduction of a conjugated double bond, desulfonylation, and reduction of various functional groups. This comprehensive review is intended to highlight the use of Mg / MeOH in each of these organic transformations.