Current Organic Chemistry - Volume 15, Issue 7, 2011

Sphingolipids (SLs) are ubiquitous membrane constituents that have emerged as essential lipid mediators involved in signal transduction and cancer development. Due to the implication of SLs in the alteration of cell proliferation, adhesion or migration, their metabolism has been targeted in search for novel anti-cancer therapeutic approaches. In this context, much attention has been directed towards SLs analogues interfering with these complex signalization pathways as well as the immune system. A general structural modulation of the basic sphingosine backbone of SLs concerns its cyclisation into various types of conformationally constrained derivatives. Different series of both natural and synthetic compounds can be considered according to this common structural feature. The present review article lists these naturally occuring sphingolipids cyclic derivatives including anhydrophytosphingosine-type marine products pachastrissamine (jaspine B), penaresidine/penazetidine, broussonetine, prosopine/prosopinine/prosophylline derivatives, as well as conceptually related synthetic products. A brief statement of their biological activity is presented. Detailed informations concerning the organic synthetic aspects are given with emphasize on the natural azetidine, pyrrolidine and all the synthetic analogues that had never been reviewed before.

This review summarizes the recent advances in the field of synthetic fragrance chemistry, with particular emphasis to the following approaches: application of known synthetic protocols to the preparation of new fragrances, lead-structure optimisation of known odorants, and stereoselective synthesis of chiral fragrances.

The review discusses two different reductive metalation approaches to the generation of benzylic organometals. In the first part, the scope of the generation of polar benzylic organometals by the reductive cleavage of carbon - heteroatom sigma bonds will be presented. Besides briefly showing the evolution of the technique, the review deals with recent achievements in the generation of benzylic derivatives of alkali metals by the reductive cleavage of carbon - halogen, carbon - oxygen, carbon - nitrogen and carbon - sulphur bonds. Significant synthetic applications of this procedure are described, showing that an appropriate choice of reaction conditions (solvent, temperature, alkali metal, employment of an electron shuttle) strongly affects the outcome of the cleavage reaction. In the second part, the application of the reductive metalation to carbon - carbon, carbon - oxygen and carbon - nitrogen double bonds is described, a procedure leading to the generation of vic-diorganometallic derivatives. Synthetic applications of these diorganometals are illustrated, underlining the possible application of 1,2-diarylsubstituted vic-dicarbanions as synthetic analogues of an activated form of an alkali metal that, however, function under homogeneous and mild reaction conditions.

The tetracyclic heteroaromatic compounds cryptolepine, isocryptolepine and neocryptolepine are all naturally occurring indoloquinoline alkaloids isolated from the shrub Cryptolepis sanguinolenta and are important due to their wide spectrum of biological properties. This review describes the isolation, brief biological activities and various synthetic methodologies developed during recent years for the preparation of this important class of alkaloids, with special emphasis on preparation and properties of cryptolepine 1, isocryptolepine 2 and neocryptolepine 3.

Many reagents have been utilized to accomplish the cyclization of organic compounds to utilize the resulting product in the synthesis of natural products and bioactive compounds. The commercially available iodine has been frequently utilized in the cyclization of several compounds such as olefinic benzyl ethers, dimethylalkenyl malonates, allylic fluorides, propargylic esters, enamides, allylated β-hydroxyketones,4,5-alkadienols, CF3-allylmorpholinones, lithium 2-(vinyl)-dithiobenzoate derivatives, 2,4-dialkenyl-1,3-dicarbonyl compounds, allylic fluorides, 1-(methylthio)-3-tosylhexa-1,3-diene-5-ynes, etc. Some of these cyclic compounds have been utilized in the synthesis of sesquiterpenes: davanone, artemone, junenol, glutinosone; diterpene pisiferic acid, iodoalkyl, dihydrofurans, β-fluorinated-γ- lactones, substituted 2-iodoindolizinones, iodinated arenes etc. The present review concentrates mainly on the recent progress of cyclization mediated by iodine. Some past examples have also been included for a comparative study.

Six new arylpiperazinylbenzofurane derivatives as potential hybrid antihypertensive agents were designed and synthesised. The discussed compounds were prepared as free bases and subsequently they were transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring in hydrochloride salts was determined by means of IR spectrometry and 13C CP/MAS and 15N CP/MAS NMR spectroscopy. Using these solid state analytical methods it was found that both nitrogen atoms were protonated. These results were supported by elemental analysis and also by ab initio/DFT calculations of partial charges and proton affinities. Physico- chemical properties of free bases and salts are discussed; especially partition and distributive coefficients log P and log D7.4, dissociation constants pKa and molecular surfaces and volumes. The experimental results were also subsequently correlated with ab initio/DFT calculations.

1,8-Naphthyridine based bi-bracchial macrocyclic 2 and cage-type macrobicyclic receptor 3 bind monosaccharides in water under physiologically relevant conditions through a combination of hydrophobic, electrostatic and hydrogen bonding interactions. The dissociation constants (Kd) for the complexes between 1,8-naphthyridine receptors 1-3 with a variety of neutral and negatively charged monosaccharides in water were determined by fluorimetric and UV/vis titration. The observed values are in the range from ˜ 0.3 to ≥10 mM, and are similar to the Kd reported for lectin/monosaccharide complexes. Among the monosaccharide substrates tested, receptor 2 showed the strongest binding affinity for sialic acid (Kd = ˜ 0.3 mM), a monosaccharide that plays many important roles in a wide variety of physiological and pathological processes. Interestingly, receptors 2 and 3 display the ability to discriminate between closely related monosaccharide substrates by opposite variation of the fluorescence emission intensity.