The separation of hypericin's enantiomers and their photophysics in chiral environments

We report the first separation of the enantiomers of hypericin. Their steady-state optical spectra and ultrafast primary photoprocesses are investigated in chiral environments. Within experimental error, there is no difference between the two enantiomers in any of the systems considered. This is consistent with the emerging picture that the rich and extended absorption spectrum of hypericin is not a result of ground-state heterogeneity. It is also consistent with the observation that the spectra and photophysics of hypericin are generally insensitive to environments in which it does not aggregate.     

Optimization of the Synthesis of 2,6–Dinitro-4-trifluoromethylphenyl Ether Substituted Cyclodextrin Bonded Chiral Stationary Phases

The comparisons of five different chiral stationary phases (CSPs) based on 2,6-dinitro-4-trifluoromethylphenyl (DNP-TFM) ether substituted β-cyclodextrin are presented. The five CSPs differ from each other in the linkage/spacer chemistry, or on the position of the substituents on β-cyclodextrin, or in the sequence of the synthetic procedure. The results show that there are two optimum combinations: (1) DNP-TFM randomly substituted on the β-cyclodextrin as the chiral selector along with a carbamate linkage chain bonding it to the silica support; and (2) β-cyclodextrin derivatized by DNP-TFM substituents only on the C-2 and C-3 positions of the cyclodextrin with an ether linkage chain anchoring it to the silica gel. These two combinations show complementary separations for some enantiomers. The spacer chain effect is much more pronounced for the CSP based on the β-cyclodextrin derivatives with DNP-TFM substituents only on C-2 and C-3 positions than its randomly substituted counterpart. The sequence of derivatizing the cyclodextrin and attaching it to silica gel also affects its selectivity and efficiency. The β-cyclodextrin should be derivatized before it is linked to the silica gel.     

Effects of partial/asymmetrical filling of micelles and chiral selectors on capillary electrophoresis enantiomeric separation: generation of a gradient

The effect of several experimental parameters on enantiomeric separations in micellar capillary electrophoresis (MCE) was studied. A model separation system was tested. It was composed of an acidic phosphate buffer with sodium dodecyl sulfate (SDS) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as the chiral selector. A substituted angelicin was used as a chiral analyte. Changes in the concentration of SDS micelles/SDS monomers in the presence of HP-beta-CD and their impact on the enantioselective separation were investigated. Variation of the composition of electrolytes in the individual compartments of the separation system (inlet vial, capillary, and outlet vial) affected both the migration times and the resolution of the enantiomers. Current vs. time dependencies also were monitored during the separations. A mathematical model of electromigration in micellar systems with chiral selector present was proposed and a computer simulation was used to explain the observed phenomena and to confirm the generation of a CD/SDS-micelle concentration gradient under certain experimental conditions. This is the reported first attempt of a computer simulation of the complex, dynamic chiral environment of the CD-SDS-MCE system.     

Stereoselective synthesis of (8R,8aS)-8-methylhexahydroindolizin-5-one

Catalytic hydrogenation of dihydroindolizidinone occurred preferentially from the endo-face giving rapid entry to (8R,8aS)-8-methylhexahydroindolizin-5-one, a key intermediate in the synthesis of 5,8-disubstituted indolizidines and deoxypumiliotoxin 251H. The selectivity could be improved further by diimide reduction though this also resulted in some oxidation of the alkene to the diene. The basis of the unusual stereoselectivity in the diimide reduction is believed to be stereoelectronic in origin.     

Stereoselective synthesis of 4-hydroxy-2-phenylproline framework

Highly diastereoselective (>20:1) bromo-lactonization of N-sulfonyl-2-allyl-2-phenylglycine methyl ester (11) was observed. Successive treatment of the chiral lactone with MeONa gave the desired (2S,4R)-4-hydroxy-2-phenylproline derivative in high yield without erosion of the diastereoselectivity. The starting chiral non-racemic compound (5) was prepared from the racemic 2-phenylglycine using a classical kinetic resolution (crystallization), an asymmetric phase transfer alkylation, and an enzyme-catalyzed kinetic resolution.     

Total synthesis of (+)-belactosin A

A concise first total synthesis of the antitumour antibiotic belactosin A is reported, involving coupling of beta-lactone carboxylic acid 3 with N-Ala-aminocyclopropyl alanine 11.     

Super/subcritical fluid chromatography chiral separations with macrocyclic glycopeptide stationary phases

The chiral recognition capabilities of three macrocyclic glycopeptide chiral selectors, namely teicoplanin (Chirobiotic T), its aglycone (Chirobiotic TAG) and ristocetin (Chirobiotic R), were evaluated with supercritical and subcritical fluid mobile phases. A set of 111 chiral compounds including heterocycles, analgesics (nonsteroidal antiinflamatory compounds), beta-blockers, sulfoxides, N-protected amino acids and native amino acids was separated on the three chiral stationary phases (CSPs). All separations were done with an outlet pressure regulated at 100 bar, 31 degrees C and at 4 ml/min. Various amounts of methanol ranging from 7 to 67% (v/v) were added to the carbon dioxide along with small amounts (0.1 to 0.5%, v/v) of triethylamine and/or trifluoroacetic acid. The Chirobiotic TAG CSP was the most effective closely followed by the Chirobiotic T column. Both columns were able to separate, partially or fully, 92% of the enantiomers of the compound set. The ristocetin chiral selector could partially or baseline resolve only 60% of the enantiomers tested. All separations were done in less than 15 min and 70% were done in less than 4 min. The speed of the separations is the main advantage of the use of SFC compared to normal-phase HPLC. In addition, SFC is advantageous for preparative separations with easy solute recovery and solvent disposal.