Sugar-based Crown Ethers in Enantioselective Syntheses

A number of chiral macrocyclic compounds have been prepared that contain a monosaccharide-derived sub-unit. These sugar-based crown ethers were used as chiral phase transfer catalysts in a few asymmetric reactions. A few of them proved to be effective catalysts in Michael additions, a Darzens condensation and an epoxidation of α,β-enones. It was found that the type of the monosaccharide, the substituents on the sugar unit and on the nitrogen atom of the macroring have a significant influence on both the yield and the enantioselectivity

Cyclopropanation of Some Alkaloids

New derivatives of natural compounds, galanthamine using in treatment of  Alzheimer’s disease and antitumor dimer alkaloids vinblastine and vincristine were synthesized. In the course of the reaction between galanthamine and diazomethane in the presence of a catalyst, such as palladium(II) acetate or copper(I) bromide, methylene insertion into the aromatic ring was observed instead of the expected cyclopropanation of the carbon-carbon double bond. New vindoline derivatives conjugated with amino acid esters were prepared. In Simmons-Smith reaction vinblastine and vincristine cyclopropanated in the carbon carbon double bond in position 14 and 15 of the vindoline monomer were obtained. New dimer alkaloids showed significant inhibiting effects in several tumor cell lines

Synthesis and recognition properties of α-d-glucose-based fluorescent crown ethers incorporating an acridine unit

Two new chiral glucopyranoside-based crown ethers incorporating acridine fluorescent signalling units, 15-membered ligand 1 and 21-membered ligand 2 were synthesized. Their complexation properties toward alkali and alkali earth metal ions, and their enantioselectivity towards chiral ammonium salts were studied by absorption and fluorescence spectroscopic experiments. Macrocycle 1 formed 1:1 complexes with all the metal ions selected and the stability constants were low (lg K < 2.3). The cavity-size of 2 allowed only the complexaton of organic ammonium ions. Crown 2 showed chiral discrimination in case of all the four ammonium salts used as model guest compounds; the highest enantioselectivity (K(R)/K(S) ~3) was observed for the enantiomers of phenylethyl ammonium perchlorate. Ligand 2 forms much more stable complexes with metal ions; the highest stability constant was obtained for the Ca2+ complex (lg K = 6.15). The coordination of metal ions by ligand 2 was accompanied by marked fluorescence enhancement, whereas the binding of ammonium ions by the same species resulted in significant fluorescence quenching. © 2014 Springer Science+Business Media Dordrecht

A study on the equilibrium reaction of benzaldehyde and sodium bisulphite by in situ Fourier transform IR spectroscopy

The addition of sodium bisulphite to benzaldehyde was monitored at different conditions by in situ Fourier transform IR spectroscopy and the equilibrium constant was determined

Attempted Diels-Alder Reactions on Vindoline Derivatives

The Diels-Alder reaction of vindoline and methyl vinyl ketone resulted in a Friedel-Crafts reaction product. In the reaction between the ortho-quinone derivative of vindoline and N-phenylmaleimide, two anomalous products were obtained, a vindoline dimer, and a condensed vindoline derivative

Királis koronaéterekkel katalizált enantioszelektív szintézisek és ''deracemizációs'' reakciók vizsgálata = Investigation of enantioselective synthesis and deracemization reactions by chiral crownethers

A monoszacharidokból felépülő királis koronaéterek aszimmetrikus indukciót képesek kifejteni bizonyos reakciókban, ha királis fázistranszfer katalizátorként alkalmazzuk azokat. Új királis metil-α-D-glükopiranozid- és α-D-mannopiranozid-alapú monoaza-15-korona-5 típusú étereket szintetizáltunk, melyek korona-gyűrűjében oxigén, kén vagy nitrogén atomok voltak, valamint foszfor atomot tartalmazó 17-korona-7 típusú vegyületeket. Vizsgáltuk a makrociklusok alkáli fém kationokkal mutatott komplexképző képességét. Néhány koronaéter katalizátorként jelentős aszimmetrikus indukciót eredményezett: a 2-nitropropán kalkonra és kalkon analgonokra történő Michael addíciójában (80-94 % ee), kalkonok terc-butil-hidroperoxiddal történő epoxidációs reakciójában (75-94 % ee) és α-klór-acetofenon szubsztituált benzaldehidekkel lejátszódó Darzens kondenzációjában (60-72 % ee) kétfázisú reakciókban. A katalizátort felépítő szénhidrát királis tulajdonsága jelentősen befolyásolja a kémiai termelést és az enantioszelektivitást. Például, amíg a D-glükopiranozidból felépülő koronaéterek a 2R,3S konfigurációjú epoxiketon keletkezését preferálták (max. 94 % ee), addig a D-mannopiranozid-alapú katalizátorok az ellentétes, 2S,3R konfigurációjú termék keletkezését segítették elő (max. 82 % ee) a kalkon epoxidációs reakciójában. Az új epoxi-ketonok abszolút konfigurációját CD spektroszkópiásan határoztuk meg. A reakciók mechanizmusát molekulamodel számításokkal bizonyítottuk. | The chiral crown ethers incorporating monosaccharide moiety in their ring, are able to general asymmetric induction as chiral phase transfer catalysts in certain reactions. New chiral methyl-α-D-glucopyranoside- and methyl-α-D-mannopyranoside-based monoaza-15-crown-5 ethers having oxygen, sulphur or nitrogen atoms in the crown ring, and 17-crown-7 type ethers containing a phosphorus atom have been synthesized. The complex forming ability of the compounds with alkali metal and ammonium cations was investigated. Some crown ethers resulted in significant asymmetric induction as catalysts in Michael addition of 2-nitropropane to substituted chalcones and heteroaromatic chalcone analogues (80-94 % ee), in the epoxidation of the different chalcones with tert-butylhydroperoxide (75-94 % ee) and in the Darzens condensation of phenacyl chloride with substituted benzaldehydes (60-72 % ee). The chiral nature of the carbohydrate in the catalyst, the quality of the side arm attached to the nitrogen atom had a significant effect on the enantioselectivity. For example the use of D-glucopyranoside-based crown ethers promoted the formation of epoxyketone with 2R,3S configuration (94 % ee), at the same time, the D-mannopyranoside-based catalyst preferred the formation of 2S,3R enantiomer (82 % ee) in the epoxidation of chalcone. The absolute configurations of epoxyketones were determined by CD spectroscopy. The mechanism of the reactions was evaluated by molecule modeling calculations