Pure Enantiomeric Forms Research Articles

Synthesis of a chiral molecular square with two organic corners

The bipyridyl ligand 5 was readily prepared in enantiomerically-pure form by coupling the appropriate stannanes with the bis-triflate 3. Mixing this ligand with a palladium ditriflate resulted in the formation of a chiral molecular square, according to spectroscopic analysis.

Stereoselective synthesis and β-blocking activity of substituted ( E)- and ( Z)-4(1H)-[1-(3-alkylamino-2-hydroxypropyl)oximino]-2,3-dihydro-1,8-naphthyridine. Potential antihypertensive agents. Part VI

Summary The synthesis of R-(+)- and S-(-)-isomers of substituted (E)- and (Z)-4(1H)-[1-(3-alkylamino-2-hydroxypropyl)-oximino]-2, 3-dihydro-1, 8-naphthyridine, in enantiomeric pure form, is described. These compounds showed an interesting β-blocking activity. Generally, the (S)-enantiomers possess a slighthly higher affinity for β receptors than the (R)-enantiomers.

Synthesis of (3S,4R)-3,4-Isopropylidenedioxy-1-pyrroline-n-oxide, an Enantiopure Functionalized Cyclic Nitrone; Cycloaddition Reactions with Dimethyl Maleate and Dimethyl Fumarate

(3S,4R)-3,4-Isopropylidenedioxy-1-pyrroline-N-oxide [(-)-4] has been prepared in enantiomerically-pure form from D-arabinose, and (+)-4 is similarly accessible from L-arabinose; cycloaddition reactions of (-)-4 with dimethyl maleate and dimethyl fumarate are reported.

Adsorption of mecoprop and dichlorprop on calcareous and organic matter amended soils: Comparative adsorption of racemic and pure enantiomeric forms

The adsorption isotherms of mecoprop [R,S‐2‐(4‐chloro‐2‐ methylphenoxy) propanoic acid] and dichlorprop [R,S‐2‐(2,4‐dichlorophenoxy)propanoic acid] on twelve calcareous soils were studied. All the isotherms fit the Freundlich equation. The distribution coefficients (Kf) were low and were only significantly related with the organic matter content of the soils. The main adsorption mechanism at the pH of these soils was found to be by cation bridging between the anionic forms of the two herbicides, and the external surfaces of the organic matter and/or negatively charged clay. The Koc values for mecoprop (R,S‐ MCPP) and dichlorprop (R,S‐ DCPP) adsorption predicted a high mobility of these herbicides in the soils. Their corresponding enantiomeric forms, R (biologically active) and S (biologically inactive) were adsorbed at the same ratio on these soils. The organic matter amended soils showed a significant increase on the retention capacity of both molecules.

Synthesis of α-phenyl-1-( R)-(−)-piperidineacetic esters

Several α-phenyl-1-( R)-(−)-piperidineacetic esters 3(a-e), were obtained in pure enantiomeric form by condensing ( R)-(−)- α-phenylglycine esters 2(a-e) with 1,5-dibromopentane. Similarly, ( R)-(−)- α-phenylglycine esters, 2(a-e), were prepared from ( R)-(−)- α-phenylglycine 1 with high yields.

Synthesis of enantiomerically pure (1R,2R)- and (1S,2S)-2-alkyl-1-phenylsulfonylcyclopropanes using Bakers’ yeast

Reduction of the ketone 1 with Bakers’ yeast gives the alcohol (R)-2 with high enantiomeric excess, and this upon subsequent epoxidation and alkylation with Grignard reagents provides the alcohols (S)-4 without racemisation. Tosylation of the alcohols (S)-4 under common conditions yields the tosylates (toluene-p-sulfonates) (S)-5, whilst under Mitsunobu conditions inversion of configuration takes place giving the tosylates (R)-5. Subsequent treatment of the tosylates (S)-5 and (R)-5 with lithium diisopropylamide leads to cyclization affording the enantiomerically pure cyclopropanes (S,S)-6 and (R,R)-6 in high yields, respectively. The diastereoisomeric alcohol (S)-4f, obtained by methylation of the alcohol (S)-4e, can also be converted into the single stereoisomer (R,R)-6f in enantiomerically pure form.

Chiral discrimination using a quartz crystal microbalance and comparison with gas chromatographic retention data

Quartz crystal microbalances (QCMB) have been constructed using 10 MHz AT cut quartz crystals coated with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, heptakis(6-O-methyl-2,3-di-O-pentyl)-β-cyclodextrin, and octakis(6-O-methyl-2,3-di-O-pentyl)-γ-cyclodextrin as 50% and 20% (w/w) solutions in OV1701. The reduction in frequency seen on exposure of each coated QCMB to pure enantiomeric forms of α- and β-pinene and cis- and trans-pinane show that statistically significant (P = 0.05, n = 7) differences are observed between the enantiomeric pairs. The apparent preferential binding shown by the QCMB for enanciomers of α- and β-pinene and cis- and trans-pinane have been compared with the elution order observed on the corresponding gas chromatographic stationary phase. The magnitude of the observed separation factor (calculated as the ratio of the OV1701 normalised frequency shift) is seen to be dependent upon the chiral stationary phase concentration. These results indicate that on-line determination of enantiomeric excess and concentration of certain monoterpenes is possible at room temperature using QCMB in conjunction with chiral gas chromatographic stationary phases. Chirality 9:225–232, 1997. © 1997 Wiley-Liss, Inc.

Enzymatic Routes for the Synthesis of Rhododendrin and Epi-Rhododendrin

The synthesis of (R)- and (S)-3-(4-hydroxyphenyO-1-methylpropyl-β-D-glucopyranosides has been achieved by two enzymatic steps, namely an oxido-reduction step involving alcohol dehydrogenases from different origin for the preparation of both aglycones in enantiomeric pure form, and a transglycosidation step involving a thermophilic β-glucosidase from the archaeon Sulfolobus solfataricus.

π‐Facial hydrogen bonding in the chiral resolving agent 2,2,2‐trifluoro‐1‐(9‐anthryl)‐ethanol and its racemic modification

Abstract2,2,2‐Trifluoro‐(9‐anthryl)‐ethanol (TFAE) has been extensively used, in its pure enantiomeric forms, as a chiral solvating agent in nuclear magnetic resonance spectroscopy (NMR). It has also played an important role in the development of chiral stationary phases in liquid chromatography (LC). X‐ray crystallography of the enantiomeric and racemic crystals shows, in both cases, the formation of an intermolecular hydrogen bond between the OH and the π‐face of one of the rings of the anthracene aromatic system.1 Few examples of such hydrogen bonding have been published previously, and those that have are not as clear cut as in this case. An explanation for the hydrogen bonding is sought using molecular modelling via the PM3 analytically derived molecular electrostatic potentials. Using NMR and dynamic lineshape analysis, the barrier to rotation about the aryl‐carbon bond is estimated, indicating the CCF3 bond to be perpendicular to the anthracene axis in nonpolar solution. This conformation is identical to the conformation in the crystal. Evidence is also presented to support the formation of intermolecular π‐facial hydrogen bonding in TFAE solutions. It is thought that such hydrogen bonding may be implicated in chiral recognition using this compound. © 1994 Wiley‐Liss, Inc.

ChemInform Abstract: Synthesis of (R)‐ and (S)‐2‐Amino‐2‐methylbutanoic Acid (Iva) in Enantiomerically Pure Form.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Stereochemical selectivity in the induction of cytochrome P450IVA1 (P452)-dependent fatty acid hydroxylation and peroxisome proliferation

Induction of hepatic microsomal cytochrome P450IVA1 and peroxisomal enzymes of the β-oxidation spiral were observed when male Long Evans hooded rats were administered optically pure enantiomeric forms and a racemic mixture of a clofibrate analogue [2-[4-(4-chlorophenyl)benzyloxy]-2-phenylacetic acid] at a dose level of 80 mg/kg for 3 days. The R(−)-enantiomer was found to be a more potent inducer of microsomal cytochrome P450IVA1 and its associated lauric acid 12-hydroxylase activity than its corresponding S(+)-antipode. This difference in potency was reflected by a eudismic ratio ( R/ S activity ratio) of approximately 3, whereas the racemic mixture exhibited a potency intermediary between the two isomers. An identical enantiomeric selectivity was observed for the phenomenon of peroxisome proliferation as judged by induction of cyanide-insensitive palmitoyl CoA oxidation and the bifunctional protein of the peroxisomal β-oxidation spiral. The highest potency was shown by the R(−)-isomer resulting in approximately a 3–6-fold increase over the control value. These increases were paralleled by an increase in total carnitine acetyl transferase activity with a eudismic ratio of approximately 4. In addition, immunochemical detection by Western blotting analysis for both the microsomal cytochrome P450IVA1 isozyme and the peroxisomal bifunctional protein was in agreement with the above modulation of catalytic activities. These results are therefore not inconsistent with the hypothesis that cytochrome P450IVA1 induction and peroxisome proliferation are intimately linked. Whether the observed stereochemical selectivity resides in xenobiotic recognition or disposition still remains to be determined.

Chiral synthesis via organoboranes. 29. A general synthesis of .alpha.-chiral monosubstituted acetylenes and their trimethylsilyl derivatives from enantiomerically pure boronic esters

The chiral monoalkylthexylborinates are prepared from enantiomerically pure boronic esters. Since chiral boronic esters of either the (+) or (−) series are readily available in essentially pure enantiomeric form, we can now synthesize both (+)- and (−)-α-chiral monosubstituted acetylenes and their trimethylsilyl derivatives of known absolute configuration and of consistently high enantiomeric excess

Review of chirality and its importance in pharmacology

AbstractWhile many pharmacologists have become increasingly aware of the importance of chirality and the role it plays in accounting for the oftentimes dramatic differences in the pharmacodynamics and pharmacokinetics of pure enantiomeric forms of therapeutic agents, there continues to be a significant lack of diligence regarding the need for properly identified stereochemicals in the scientific literature. All too frequently published reports and textbooks fail to adequately identify the stereochemical nature of the drugs utilized in a study Since the individual components of an enantiomeric pair typically have significant differences in their pharmacologic activities, the need for unambiguous descriptive nomenclature is evident. This review presents a summary of the various types of nomenclature utilized in the pharmacologic literature and their chemical bases. Several examples are described which illustrate the significant differences between enantiomeric forms of drugs and suggest possible theoretical bases for such differences. The need for continued awareness on the part of pharmacologists and the proper, unambiguous identification of stereolsomers in the scientific literature and labeling is stressed.

Competitive inhibition of lipolytic enzymes. II. Preparation of ‘monoacylamino’ phospholipids

This paper describes the synthesis of a number of phosphatidylcholines and phosphatidylglycols, in which one fatty acyl ester group is replaced by an acylamino function. The phospholipids, both of the α- and β-type, are prepared in racemic and enantiomeric pure forms.

Water-promoted claisen sigmatropic rearrangement using glyco-organic substrates. Chiral auxiliary-mediated induction

The Claisen sigmatropic rearrangement with glyco-organic substrates is greatly accelerated in water. Moreover, the ability of glucose to function as a chiral auxiliary is illustrated in the preparation of 4-pentene-1,3-diol, obtained for the first time in pure enantiomeric form.

A molecular approach of poly(thiophene) functionalization

The effects of the monomer molecular structure on the properties of the resulting substituted conducting poly(thiophenes) have been analyzed with as main objective the definition of the basic structural conditions for introducing a given functionalized group while preserving the electronic and electrochemical properties of the conducting backbone. Various substitutions of the thiophene ring by linear and branched alkyl chains, ethers and aromatic groups are discussed in regard to their consequences on the electropolymerization reaction and on the electrochemical, spectroscopic and electrical properties of the resulting polymer. The conclusions of these analyses are applied to the design of highly conducting chiral poly(thiophenes). When prepared in pure enantiomeric form, these polymers present high specific rotation and are capable to recognize the two enantiomeric forms of chiral anions used as dopant during redox cycles.

Synthesis of 4,6-diedoxy- d- and - l-hexoses from racemic and meso-dipropenylglycol

Rac- and meso-divinylglycols offer, via site-selective epoxidation, a versatile strategy for the synthesis of optically pure sugars. This is exemplified in this paper by the synthesis of 4,6-dideoxyhexoses. Starting from mono- O-benzyl di-(1-propenyl)glycol, readily obtained from racemic-di-1-propenylglycol[(±)- 1] with the help of Sharpless epoxidation, the 3 d and 3 l diol-epoxides, respectively, were synthesized in enantiomeric pure form. Regioselective reductive cleavage of the epoxide ring and ozonolysis of the CC-double bond gave 2- O-4,6-dideoxy- d- and - l- xylo-hexose ( 5 d and 5 l) respectively, in only four steps from racemate[(±)- 1]. The transformation of compound 5 l into l-chalcose is described. Similarly, mono- O-benzylation of meso-dipropenylglycol and subsequent Sharpless epoxidation in the presence of diethyl (+)-tartrate gave selectively an l-diolepoxide, which was transformed readily into 4,6-dideoxy- l- lyxo-hexose and 4,6-dideoxy-3- O-methyl- l- lyxo-hexose.

Assymetric syntheses of the ladybug alkaloid adaline and 1-methyl-9-azabicyclo [3.3.1]nonan-3-one

The double Michael addition of benzylamine to 3-alkyl-2,7-cyclooctadienones, followed by hydrogenolysis, affords bridgehead substituted 9-azabicyclo[3.3.1]nonan-3-ones. Use of (+)-α-methylbenzylamine in the addition leads to mixtures of diastereomeric adducts in unequal amounts. Although the degree of asymmetric induction is low (10–20% ee), the diastereonomers can be easily separated, affording pure enantiomeric forms of the ladybug alkaloid adaline 1 and the Euphorbia alkaloid 3.