Epimers Research Articles

Molecular structure, proton affinity and hydrogen bonds of (2-hydroxyethyl)amine-N-oxides: DFT, MP2 and FTIR study

Tris- 1, bis- 2, and mono- 3 (2-hydroxyethyl)amine-N-oxides isomers, their protonated forms, and H-complexes with acids have been studied in gas phase and DMSO solution by the quantum chemical calculations using DFT and MP2 methods. It is found that the proton affinity of the endo isomers 1a–3a, exo isomers 1b–3b and epi isomer 1c depends on the number of the hydroxyethyl groups, steric factors and strengths of the intramolecular H-bonds OH⋅⋅⋅ON in 1a–3a and OH⋅⋅⋅OH in 1b–3b. The peculiarities of formation of the hydrogen bonded and proton transfer complexes of tris(2-hydroxyethyl)amine-N-oxide with trifluoroacetic and 2-methylphenyloxyacetic acids are defined by 1 configuration, acid strength and solvent polarity. The structure of 1 and its complexes upon transition to solution was determined using FTIR spectroscopy.

Synthesis of diospongin A, ent-diospongin A and C-5 epimer of diospongin B from tri-O-acetyl-D-glucal

Synthesis of diospongin A, ent-diospongin A and C-5 epimer of diospongin B from tri-O-acetyl-D-glucal

High dose C‐3 alpha epimer of 25‐hydroxyvitamin D over 8 weeks reduces cortical mineral density of lumbar vertebra in weanling rats (828.2)

C‐3 alpha epimer (EPI) of 25‐hydroxyvitamin D (25(OH)D) is elevated in infancy. Short‐term treatment with the EPI of calcitriol reduces parathyroid hormone (PTH) in rats. This study tested the effect of EPI on growth, bone biomarkers and volumetric bone mineral density (vBMD). Weanling rats (4 wk; n=6 male; n=6 female/diet) were randomized to receive AIN‐93G diets modified in vitamin D for 8 wk: control AIN‐93G (C‐1: 25 µg vitamin D3/g diet), control 25(OH)D (C‐2: 12.5 µg 25(OH)D/g diet), level one EPI (EPI‐1: 12.5 µg EPI/g diet) or level two EPI (EPI‐2: 25 µg EPI/g diet). Measures were weight and biomarkers at 0, 4 and 8 wk and in vivo lumbar vertebra 3 vBMD using microcomputed tomography (LCT‐200, Aloka) at 0 and 8 wk. Differences among groups were tested using ANOVA, Tukey’s post hoc test and P<0.05. No differences in vitamin D status as measured using LC‐MS/MS were observed at baseline. Average serum EPI (range ng/ml) at 8 wk was C‐1: 4 (0‐12), C‐2: 2 (0‐7), EPI‐1: 49 (27‐78) and EPI‐2: 98 (41‐173). Weight, ionized Ca and C‐telopeptides of Type 1 collagen were not affected by diet. PTH was lowest in EPI‐2 vs all groups at wk 4; and lower in EPI‐1 and EPI‐2 vs C‐2 at wk 8. Cortical vBMD was lowest in EPI‐2 vs all other groups at wk 8; but not trabecular or total vBMD. These data suggest that pharmacological concentrations of EPI reduce PTH and cortical density during rapid growth.Grant Funding Source: Supported by NSERC and Dairy Farmers of Canada

Studies on the Diels-Alder adduct from cyclopentadiene and p-benzoquinone: Biotransformation, enantiomeric excess and absolute configuration

The use of microorganisms or isolated enzymes in synthetic routes has been extensively used by industry and academic research. A great advantage of biotransformation in a synthetic route is highly regio- and enatiosselective control, which can be achieved through microbial catalyzed reaction. Biotransformation is one of the most efficient methods in a production of high purity optical compounds and development of efficient routes for target molecules. Biotransformation by Mucor ramosissimus of enedione 1 gave the keto-alcohol (-)-2 with enantiomeric excess (ee)>99,9% (determined by 1 H NMR with [(+)-Eu(hfc)] 3 ) and their epimer (-)-3 . Determination of the absolute configuration of epimer (-)-3 was accomplished by controlled reaction and measuring of optical rotation (scheme 1). The fungus M. ramosissimus is a promising species to perform desymmetrization of diketones with high enantioselectivity.

Structure and absolute configuration of 3-alkylpiperidine alkaloids from an Indonesian sponge of the genus Halichondria

Chemical analysis of an Indonesian sponge sample has provided three new 3-alkylpiperidine alkaloids, tetradehydrohaliclonacyclamine A, its mono- N-oxide derivative, and a 2- epi isomer. The absolute structure of tetradehydrohaliclonacyclamine A has been established by X-ray crystallography from anomalous dispersion effects using Cu radiation, which determined that the absolute configuration is 2 S, 3 S, 7 S, 9 S while an HPLC study revealed that the alkaloid is enantiomerically pure.

Synthesis and biological activity of previtamin D 3 analogues with A-ring modifications

Synthesis of two novel 6- s- cis analogues of 1α,25-dihydroxyvitamin D 3 are described using shikimic acid and its 4- epi isomer as versatile chiral starting materials. These derivatives contain a 2β-(3′-hydroxypropoxy) moiety or a 2β,3β-epoxy group into 1α,25-(OH) 2-19- nor-pre-D 3. The synthesized analogues were found to be not suitable for binding to the vitamin D receptor and showed weak binding affinity toward the vitamin D-binding protein. The new derivatives failed to inhibit cell proliferation.

Total synthesis of malyngamide X and its 7′ S- epi isomer

Stereoselective syntheses of malyngamide X ( 1) and its 7′( S)-epimer are described. A Lewis acid (Et 2AlCl) mediated anti-aldol reaction was employed to generate the stereocenters C-7 and C-8. The route is convergent and provides a convenient access to the synthesis of structural variants of malyngamide X. Stereochemistry at C-7′ in the molecules of natural and synthetic 1, and 7′( S)- epi 1 was confirmed by NMR chiral solvation experiments.

Identification of cubebin and epicubebin isolated from Piper cubeba L.f fruits with two D-NMR spectroscopy

One of the isolated active compound of the tracheospasmolytic from kemukus fruits (Piper cubeba L.f) is cubebin. The problem occurred when cubebin (C20H20O6) mixed with its epimer because of the difficultly to identify the structure by 1D-NMR spectroscopy. Structure identification then was conducted by 2D-NMR spectroscopy, so the structure of cubebin and epicubebin can be clear identified. Key words : Cubebin, epicubebin, identification, 2D-NMR

Stereochemistry of 3,4‐Dihydroexcelsin.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Polyhydroxylated pyrrolizidines. Part 6: A new and concise stereoselective synthesis of (+)-casuarine and its 6,7-di epi isomer, from DMDP

A new synthesis for (+)-casuarine ( 1 ) and its 6,7-di epi isomer ( 15 ) in a stereocontrolled manner, is reported herein. An appropriately protected polyhydroxylated pyrrolidine, such as (2 R,3 R,4 R,5 R)-3,4-dibenzyloxy-2′- O- tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine ( 3 , protected DMDP), easily available from d-fructose, was chosen as the chiral starting material. Compounds 1 and 15 were obtained from 3 , in seven steps, in a 23.2 and 20.5% overall yields, respectively.

Synthesis of 7‐Oxa‐phomopsolide E (I) and Its C‐4 Epimer.

Synthesis of 7‐Oxa‐phomopsolide E (I) and Its C‐4 Epimer.

Chlorosphaeropsidone and Epichlorospaeropsidone, Two New Chlorinated Dimedone Methyl Ethers Isolated from Liquid Cultures of "Sphaeropsis sapinea" f. sp. "cupressi"

Two new dimedone methyl ethers, named chlorosphaeropsidone and epichlorosphaeropsidone were isolated from the culture filtrates of Sphaeropsis sapinea f. sp. cupressi, the causal agent of a canker of Italian cypress (Cupressus sempervirens L.). The same fungus also produced various phytotoxic metabolites: three pimarane diterpenes (sphaeropsidins A, B and C) and two dimedone methyl ethers (sphaeropsidone and episphaeropsidone). Chlorosphaeropsidone and epichlorosphaeropsidone were characterized using chemical and spectroscopic methods as two 6-chloro-4,5-dihydroxy-3-methoxycyclohex-2-en-1-ones epimers at C-6. Their relative and absolute configurations were established by NMR, X-ray analysis and circular dichroism. Assayed on host plants they did not show phytotoxic activity. Comparison with other sphaeropsidones suggested that this might result from opening of the epoxy ring.

New syntheses of two epimers of (+)-castanospermine: (+)-8a- Epi- and (+)-1,8a-Di- epi-castanospermine

Two epimers of (+)-castanospermine, (1 S,6 S,7 R,8 R,8a S)-1,6,7,8-tetrahydroxyindolizidine [(+)-8a- epi-castanospermine] ( 4) and (1 R,6 S,7 R,8 R,8a S) derivative [(+)-1,8a-di- epi-castanospermine] ( 5) were synthesized from methyl α-D-glucopyranoside.

Regiospecific bromination-cyclization of spirocyclic cyclohexanones and its application to the synthesis of (±)-laurencial

Stereospecific bromination-cyclization of spirocyclic cyclohexanones having an isopropylidenedioxy group was found to proceed under thermodynamically controlled conditions, which was applied to the first synthesis of (±)-laurencial and its epimer.

Synthesis and crystal structure of a novel chiral compound prepared from (-)-borneol as a natural chiral auxiliary

The solid diastereoisomeric mixture4a+4b was obtained via the asymmetric Michael addition reaction of phenylthioalcohol with liquid epimeric mixture 5-(-)-bornyloxy-2(5H)-furanone3a+3b, which was prepared by reaction of the natural abundant chiral auxiliary borneol 2 with 5-hydroxy-2(5H)-furanone 1. The two diastereoisorners4a +4b were separated by means of preferential cyrstallization, which gave one optically pure compound4b with de > 98 %. The absolute configuration of4b was established by X-ray crystallography. The method provided a new efficient route for utilizing natural chiral auxiliaries and preparing optically pure diastereoisomeric compounds based on liquid epimers.

Fluorinated analogues of nojirimycin and mannojirimycin from a non-carbohydrate precursor

1,3,5-Trideoxy-3-fluoronojirimycin 3a and its 5- epi isomer 3b have been synthesized in enantiomerically pure form starting from the fluorohydroxysulfinylhexene (2 R,3 S, S S)- 6. The nitrogen atom of the target bioactive compounds is introduced by replacing the sulfinyl group with an hydroxylamine residue and an intramolecular aminomercuration reaction builds up the desired piperidine ring. Finally, an oxidative demercuration affords the hydroxymethyl moiety. The same synthetic sequence allows to obtain 1,3,5-trideoxy-3-fluoromannojirimycin 4a and its 5- epi isomer 4b starting from the benzyloxy-fluorosulfinylhexene (2 S,3 S, R S)-7.

A Convenient Synthesis of C-8 Oxo-eudesmane. Total Synthesis of (±)-Eudesma-5,7(11)-dien-8-one

Abstract The synthesis of (±)-eudesma-5,7(11)-dien-8-one 5 was accomplished in 5 steps from the known octalone 6. Reduction of the enone 5 with LAH followed by acetylation, furnished the mixture of (±)-coralloidin-A (11) and its C-8 epimer 12 in a ratio 2:1.

Energy-dependent export of leukotriene B 4 in Xenopus oocytes

The export of leukotriene (LT) B 4 was studied using the Xenopus oocyte system. The oocytes were microinjected intracellularly with [ 3H]LTB 4, and the export/injection ratios were determined. The ratios decreased with increasing doses of LTB 4, converging upon 4%. The export was temperature-dependent and decreased with ATP depletion, thereby suggesting that the export is energy-dependent and carrier-mediated. The LTB 4 export was inhibited by 6- trans-LTB 4 and its 12- epi isomer, but much less by LTD 4. Neither verapamil nor quinidine significantly inhibited LTB 4 export. These results suggest that oocytes have an export system specific for LTB 4 and its isomers, and that the multidrug-resistant transporter is not involved in this system. By contrast, much of platelet-activating factor, another lipid mediator, was retained in oocytes at different temperatures after injection. It was thus shown that the two potent lipid mediators are exported from cells in a different manner and that oocytes are a good model for analyzing export systems for bioactive mediators.

NMR Studies on the Configuration of 6-Chloro Nitrile Epimers of Tropane Derivatives

Baogongteng A is a tropane alkaloid with cholinergic activity. It has been used clinically for the treatment of glaucoma, and its pharmacological activity on heart function has also been reported.In the synthesis of baogongteng A, the cycloadducts of Katritzky cycloaddition of 1-benzyl-3-oxidepyridinium with a-chloroacrylonitrile were ketalized with ethylene glycol in benzene by azeotropic distillation. After recrystallization from ethanol, two compounds(A, prisms, m.p.127—129℃; B, needles, m.p.75—77℃) were obtaines.Their MS, IR spectral data and elemental analysis were consistent with the proposed structures. They were assigned as C_6-chloro nitrile epimers by ~1H-~1H homonuclear

Thin-layer chromatographic detection of glucocorticoids.

An adsorption thin-layer chromatography (TLC) is described for the detection of glucocorticoids including triamcinolone, prednisolone, 6 alpha-methylprednisolone, betamethasone, dexamethasone, hydrocortisone, prednisone and cortisone. Separation of the glucocorticoids was performed on a silica stationary phase with chloroform-dioxane-methanol (15:4:1, v/v) as a mobile phase. The complete resolution of the epimers of betamethasone and dexamethasone was attained by derivatization of them with (1S)-(-)-camphanic chloride using triethylamine as a catalyst. The application of the method to the analysis of glucocorticoids in various samples is being smoothly developed.