Enantiomer最新文献

In the course of synthetic studies of chiral olefins, (3R,3'R)-(P,P)-(E)-(-)-1,1',2,2',3,3',4,4'-octahydro3,3'-dimethyl-4,4'-biphenanthrylidene (1) and its (3R, 3'R)-(P,P)-(Z)-(+)-isomer (2), chiral (3R,3'R,4R,4'R)-(-)-1,1',2,2',3,3',4,4'-octahydro-3,3'-dimethyl-4,4'-biphenanthryl (3) was obtained as a by-product in the McMurry reaction of (3R)-(-)-2,3-dihydro-3-methyl-4(1H)-phenanthrenone (4). The relative and absolute stereostructures of (-)-3 were fully determined by NMR, X-ray crystallographic, and CD spectral analyses.

Enantiopure [8]paracyclophane-10-carbonitrile (1) and related compounds were prepared. The absolute stereochemistry of [CD(+)242.0]-1 was determined to be R by theoretical calculation of its CD spectrum using the pi-electron SCF-CI-DV MO method. The theoretical determination came to the same conclusion as the X-ray crystallographic method had previously given. Other related compounds show similar CD spectra leading to the R absolute stereochemistry.

Enantioselective transesterification of 1-phenyl-1-alkanols (PhCH(OH)(CH2)n-2CH3; n = 2, 3, 4, 5, 6, 9, 12, 18) with vinyl acetate catalyzed by lipases in benzene has been studied to find the catalyst which is generally used for preparing optically active 1-phenyl-1-alkanols having various alkyl chains. Amongst lipases examined (lipases LIP, PS, AK, CAL and RML), the lipase from Pseudomonas aeruginosa (LIP) is the best catalyst which shows high reactivity and enantioselectivity and low substrate specificity. The rate of the LIP-catalyzed transesterification decreases with increasing the alkylchain length till n = 4. The catalysis of LIP recovers again toward the alkanols with n = 5-18. Other lipases do not exhibit such an effect of alkyl-chain length and show very poor or no catalysis for the alkanols with n > or = 4. LIP is also the best catalyst for the enantioselective transesterification of 1-(1-naphthyl)-, 1-(2-naphthyl)- and 1-(1-pyrenyl)-1-propanols. Each optically pure 1-aryl-1-alkanol was isolated by the present method.

2,6-Dimethylspiro[3.3]heptane-2,6-dicarboxylic acid (2), an analog of the Fecht acid (1), was enantioresolved by the method of (1S,2R,4R)-(-)-2,10-camphorsultam yielding enantiopure acid (+)-2, the S absolute configuration of which was unambiguously determined by X-ray crystallography of camphorsultam amide derivative (R)-(-)-12b and chemical correlation. To determine the absolute configuration of chiral spiro[3.3]heptane compounds by the circular dichroism (CD) exciton chirality method, acid (+)-2 was converted to (+)-2,6-bis(phenylacetylenyl)-2,6-dimethylspiro[3.3]heptane (3) and (+)-2,6-bis(4-methoxyphenylacetylenyl)-2,6-dimethylspiro[3.3]heptane (4). The CD spectra of (+)-3 and (+)-4 exhibit intense exciton split Cotton effects of positive chirality, from which their S absolute configurations were confirmed.

HPLC chiral stationary phases based on human plasma alpha1-acid glycoprotein (AGP) and partially deglycosylated AGP (pd-AGP) were prepared to investigate the effects of sugar moiety of AGP on chiral discrimination of various solutes. Removal of a sugar moiety of AGP by treatment with N-glycosidase was confirmed by high-performance capillary electrophoresis, reversed-phase HPLC and matrix-assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry. The average molecular weights of AGP and pd-AGP were estimated to be ca. 33,000 and 30,600, respectively, by MALDI-TOF mass spectrometry. Next, AGP and pd-AGP were bound to aminopropyl-silica gels activated with N,N '-disuccinimidylcarbonate. The retentivity+ and enantioselectivity of the neutral, acidic and basic solutes tested on the pd-AGP column were significantly or not significantly larger in most solutes than those on the AGP column. This is ascribable to that by cleavage of a sugar chain(s) by N-glycosidase, pd-AGP could become more hydrophobic than AGP, and/ or that a solute could be easily accessible to the specific and/or non-specific binding sites of pd-AGP. It is interesting that warfarin enantiomers are not resolved on the pd-AGP column, but resolved on the AGP column. A sugar chain(s) of AGP cleaved by N-glycosidase might be involved in the enantioselective binding of warfarin enantiomers.

Looking for more efficient sandalwood oil smelling compounds, new campholenic aldehyde derivatives with rigidifying cyclopropane rings were prepared. For some of them, having the lowest odor threshold ever measured for this type of odorants and a very appreciated scent, close to that of the scarce natural sandalwood oils, pure stereoisomers were obtained and their olfactory properties were evaluated. Thus acquired structure-odor relationship data, together with consolidated and completed previous knowledge on structurally different sandalwood-smelling compounds, allowed to propose new models of the sandalwood olfactophore.

The formation and separation of diastereomers is widely used to resolve enantiomers. However, during crystallization of a chiral compound from a solution containing its diastereomer, the diastereomer may be incorporated as an impurity into the host crystal lattice, leading to changes in the thermodynamic properties and intrinsic dissolution rate of the host crystals. This hypothesis was tested by growing crystals of (SS)-(+)-pseudoephedrine hydrochloride (+PC) from aqueous solution containing various amounts of (RS)-(-)-ephedrine hydrochloride (-EC). Although the melting phase diagram of these two solid compounds, determined by differential scanning calorimetry (DSC), shows eutectic behavior, 0.034-2.4 mol% of -EC was incorporated into the crystal lattice of +PC during crystallization to form terminal solid solutions with a segregation coefficient of 0.31. In a single batch, the larger crystals contain more incorporated impurities than smaller crystals. The enthalpy and entropy of fusion measured by DSC decrease with increasing incorporation of the guest molecules into the host, indicating increases in the enthalpy and entropy of the solid. The disruption index, which indicates the disruptive effect of guest molecules in the host crystal lattice, is 60 at < or = 0.084 mol% of -EC in +PC crystals, but is only 5 at higher levels of -EC. The greater disruptive effect at lower levels of impurity incorporation may be explained by the formation of substitutional solid solutions in which the impurity molecules disrupt the hydrogen bonding network in the host crystals, whereas additional incorporated impurity may be adsorbed onto the surfaces of the mosaic blocks with reduced effect on the crystal lattice. The average intrinsic dissolution rate of impure crystals in 2-propanol is 15.8% lower than that of pure host crystals, suggesting the formation of stable solid solutions.

The configurational analysis of beta-lactams prepared from [2 + 2] cycloaddition of vinyl ethers to pure enantiomers of 1-arylethyl isocyanates was carried out by high resolution 1H NMR. The addition of a chiral shift reagent revealed that the most important conformation of the studied beta-lactams in solution is that in which the methine proton, of the exocyclic stereogenic carbon, points towards the carbonyl oxygen atom. Since the configuration of the stereogenic exocyclic carbon is known, the orientation of the aromatic ring allows the correlation of the chemical shifts with the absolute configuration of the new stereogenic centers. This method is particularly useful to establish the stereochemistry of oily beta-lactams having the N-(1-arylethyl) group. The X-ray crystallographic analysis carried out with (1R,5S)-7-[(1S)-1-(1-naphthyl) ethyl]-2-oxa-7-azabicyclo[3.2.0]heptan-6-one, is consistent with the proposed model for beta-lactams in solution.

Various arylcarbinol esters were resolved on a commercial chiral column, (S, S) Whelk-O1. Among others, the analytes in which the aryl group is in conjugation with the double bond(s) to the chiral center were resolved much better on (S, S) Whelk-O1 than the corresponding non-double bonded analytes. From these results, it was proposed that the double bond pi-conjugation of the aromatic group of racemic analytes is very important for the chiral recognition. In addition, the size of the acyl group of arylcarbinol esters has been demonstrated to be important for the chiral recognition. In general, the large acyl group such as pivaloyl group was very effective for the chiral recognition of arylcarbinol esters on (S, S) Whelk-O1.

Enantiomers of spiro-lambda 4-sulfanes 2-7 and related cyclic sulfonium salts 2c-7c have been obtained by stereospecific synthesis. Exciton splitting was observed in the CD spectra of spiro-lambda 4-sulfanes and sulfonium salts having both benzene and naphthalene-benzene rings. The absolute configurations were deduced from the sign of the couplet. Exciton couplets in the CD spectra of sulfonium salts and their parent lambda 4-sulfanes show the same sign which follows from the same orientation of the coupled electric transition moments due to their similar trigonal bipyramidal geometry. Based on the known stereomechanism of the formation of spiro-lambda 4-sulfanes and sulfonium salts as well as of their hydrolysis leading to the corresponding sulfoxides (2a-7a and 2b-7b), the absolute configurations of sulfoxides could also be deduced from the sign of exciton couplet in the CD spectra of related lambda 4-sulfanes and sulfonium salts.