Retention Of Enantiomeric Purity Research Articles

Inherently Chiral Cages via Hierarchical Desymmetrization.

A new type of cage inherent chirality was accessed by hierarchical desymmetrization of a D3h-symmetric prismlike cage motif. The dissymmetric C3v cage precursor C1 bearing two different phloroglucinol caps was first synthesized. The subsequent progressive substitutions on the three triazine arms by different nucleophiles furnished the desired C1-symmetric inherently chiral cages C3 and C4 with rich structural diversity. Resolution of the racemic cages was achieved by chiral chromatography, and the enantiopure cages were readily obtained on the gram scale. Convenient post-synthetic transformations of the chiral cages with retention of enantiomeric purity were also realized. The absolute configuration was determined by X-ray crystallography, and a chirality descriptor was provided to define the cage chirality. With the inherently chiral array of the electron-deficient triazine surfaces constituting three individual chiral V-shaped π cavities, regio- and enantioselective anion-π binding was probed for the first time with minimum interference of other interactions. As exemplified with chiral phosphate anions (CPAs), it was found that cage (-)-C3a preferably binds (S)-CPA- in the most electron-deficient cavity through synergistic anion-π interactions with considerable chiral selectivity.

Stereoretentive Deuteration of α-Chiral Amines with D2O.

We present the direct and stereoretentive deuteration of primary amines using Ru-bMepi (bMepi = 1,3-(6'-methyl-2'-pyridylimino)isoindolate) complexes and D2O. High deuterium incorporation occurs at the α-carbon (70-99%). For α-chiral amines, complete retention of stereochemistry is achieved when using an electron-deficient Ru catalyst. The retention of enantiomeric purity is attributed to a high binding affinity of an imine intermediate with ruthenium, as well as to a fast H/D exchange relative to ligand dissociation.

No carrier added synthesis of O-(2′-[ 18F]fluoroethyl)- l-tyrosine via a novel type of chiral enantiomerically pure precursor, Ni II complex of a ( S)-tyrosine Schiff base

O-(2′-[ 18F]fluoroethyl)- l-tyrosine ([ 18F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of 18F (110 min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [ 18F]FET, based on NiII complex of a Schiff’s base of ( S)-[ N-2-( N′-benzylprolyl)amino]benzophenone (BPB) with alkylated ( S)-tyrosine, Ni-( S)-BPB-( S)-Tyr-OCH2CH2X (X = OTs ( 3a), OMs ( 3b) and OTf ( 3c)). A series of compounds 3a– c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of ( S)-isomer and ( R, S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a– c (4.5–5.0 mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 °C for 5 min, followed by (2) removal of protective groups by treating with 0.5 M HCl (120 °C, 5 min). The major advantages of this procedure are retention of enantiomeric purity during the 18F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a– c. Radiochemically pure [ 18F]FET was isolated by semi-preparative HPLC (C18 μ-Bondapak, Waters) eluent aq 0.01 M CH 3COONH 4, pH 4/C 2H 5OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55 min. In a series of compounds 3a– c, tosyl derivative 3a provided highest radiochemical yield (40–45%, corrected for radioactive decay). Enantiomeric purity was 94–95% and 96–97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat’s tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.

An enantiomeric palladium derivative of ferrocene as an asymmetry inducer in the synthesis of optically active glycerides

Carbonylation of the readily available optically active 1-chloropalladio-2-dimethyl-aminomethylferrocene (I) in the presence of prochiral 2-0-benzylglycerin leads to glyceride (II). In accord with our hypothesis, the generation of the chiral center at C/sup 2/ in the glycerin segment of the molecule is accompanied by asymmetric induction. This results in a mixture of unequal amounts of the diastereomers of (II). The tritylation of this mixture with subsequent alkaline deacylation of (III) leads to enantiomeric (IV), which is a key intermediate for the synthesis of glycerides. Derivative (IV) may be converted by ordinary chemical methods with retention of enantiomeric purity into mono-, di- and triacyl or alkyl glycerin derivatives as shown in the case of the synthesis of 1-O-palmitoyl-snglycerin (V). S/rho//sup -/(I) predominantly induces the natural S configuration of the C/sup 2/ center in the glyceride. The extent of asymmetric induction in the carbonylation of (I)determined both by NMR analysis of the diastereomeric composition of (III) and the optical rotation of (V) is 36 +/- 2%.