Absolute Configuration Of Chiral Centers Research Articles

Benchmarking Guanidinium Organosulfonate Hydrogen-Bonded Frameworks for Structure Determination of Encapsulated Guests.

Single crystal X-ray diffraction (SCXRD) is arguably the most definitive method for molecular structure determination, but it is often challenged by compounds that are liquids or oils at room temperature or do not form crystals adequate for analysis. Our laboratory previously reported a simple, cost-effective, single-step crystallization method based on guanidinium organosulfonate (GS) hydrogen bonded frameworks for structure determination of a wide range of encapsulated guest molecules, including assignment of the absolute configuration of chiral centers. Herein, we expand on those results and report a head-to-head comparison of the GS method with adamantoid "molecular chaperones", which have been reported to be useful hosts for structure determination. Inclusion compounds limited to only two GS hosts are characterized by low R1 values and Flack parameters, infrequent disorder of the host and guest, and manageable disorder when it does exist. The structures of some target molecules that were not included or resolved using the adamantoid chaperones were successfully included and resolved by the GS hosts, and vice versa. Of the 32 guests attempted by the GS method, 31 inclusion compounds afforded successful guest structure solutions, a 97% success rate. The GS hosts and adamantoid chaperones are complementary with respect to guest inclusion, arguing that both should be employed in the arsenal of methods for structure determination. Furthermore, the low cost of organosulfonate host components promises an accessible route to molecular structure determination for a wide range of users.

Deoxofluorination of Aliphatic Carboxylic Acids: A Route to Trifluoromethyl-Substituted Derivatives.

A practical method for the synthesis of functionalized aliphatic trifluoromethyl-substituted derivatives from aliphatic acids is developed. The transformation proceeds with sulfur tetrafluoride in the presence of water as a key additive. Compared to previous methods, the reaction gives products with full retention of stereo- and absolute configuration of chiral centers.

Asymmetric Total Synthesis of 16‐Methyleicos‐(4E)‐en‐1‐yn‐3‐ol from the Marine Sponge Cribrochalina vasculum: Establishment of Absolute Configuration of Chiral Centers

AbstractThe first total synthesis of 16‐Methyleicos‐(4E)‐en‐1‐yn‐3‐ol, a bioactive component of the marine sponge Cribrochalina vasculum was achieved by Evans auxiliary methylation followed by resolution of the corresponding racemates using lipase formulation Novozyme 435 and Mosher's ester method. We report the asymmetric syntheses of four diastereomers (1 a‐d) of the natural compound 1 and established the absolute configuration of chiral centers, leading to the revision of the natural product configuration from 3 S to 3 R.

Anti-inflammatory activity of caffeic acid derivatives isolated from the roots of Salvia miltiorrhiza Bunge.

Ten caffeic acid derivatives (1-10) were isolated from the roots of Salvia miltiorrhiza by using various chromatographic methods and their chemical structures were spectroscopically elucidated. The absolute configurations of chiral centers were determined by comparison with reported coupling constants, optical rotation values, and CD techniques. Anti-inflammatory activities were evaluated using nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 inhibition assays, and by determining the expression of heme oxygenase (HO)-1. Two new caffeic acid derivatives, 8-epiblechnic acid 9-methyl ester (4) and 8-epiblechnic acid 9'-methyl ester (5), and eight known derivatives, caffeic acid methyl ester (1), shimobashiric acid B (2), rosmarinic acid methyl ester (3), salvianolic acid C (6), methyl salvianolate C (7), lithospermic acid monomethyl ester (8), lithospermic acid dimethyl ester (9), and dimethyl lithospermate B (10), were isolated from the ethyl acetate fraction of S. miltiorrhiza. All caffeic acid derivatives were evaluated for their inhibitory effect on NO production. Compounds 2 and 3 inhibited NO production with IC50 values of 1.4 and 0.6μM, respectively. These compounds also strongly inhibited the production of iNOS and COX-2. In addition, compound 3 induced the expression HO-1 in a concentration-dependent manner at 0.1, 0.3, and 1.0μM.

Synthesis of 1,10-seco-triterpenoids by the Beckmann fragmentation from allobetulin

A new convenient route to synthesize 1,10-seco-triterpenoids from allobetulin was demonstrated. Stereoisomerism of starting oleanane 1-oximes was determined by X-ray crystallography and additionally confirmed by the structure of the obtained Beckmann rearrangement products. Absolute configuration of chiral centers of 1,10-secotriterpenoids was found to be identical to that of stereocenters in respective precursors. Antiviral activity of 1,10-seco-derivatives was studied against herpes simplex virus type I.

Effect of ferroelectric liquid crystalline quaterphenyl structure and handedness on helical pitch length in bicomponent mixtures

ABSTRACTThe aim of this paper is characterisation of mesomorphic properties and helical structure parameters: handedness and helical pitch, of two laterally substituted ferroelectric compounds and mixtures based on them. These compounds have the same quaterphenyl rigid core and the same length of non-chiral chain – eight carbon atoms, as well as the absolute configuration of chiral centre (‘R’). Base compounds differ in the kind of a substituent in a rigid core (–Cl, –CH3). Both of them have rather low melting temperature in comparison to most of quaterphenyls, and it affects the lowering of this temperature in binary mixtures. Thus they can be used for preparation of multicomponent ferroelectric mixtures useful for application.

Synthesis of 1-azabicyclo[3.2.2]nonane from cinchonidine

The 1-azabicyclo[3.2.2]nonane is a potent building block which have important bio­logicaly activities including for Alzheimer and ashmatic treatment. The skeleton can be accessed by rearrangement of quinuclidine ring in Cinchona alkaloids. The rearrange­ment established three chiral center at C-2, C-3, and C-6. The rearrangement of qui­nuclidine moiety to azabicyclic[3.2.2]nonana system of mesylated cinchonidine took place by hydrolysis in a mixture of acetone–water (1:1) with 47% yields. The structure determination of the product and its absolute configuration of chiral centers were esta­blished by using spectroscopy data including, 1H NMR, 13C NMR, 1D NOE and HR-MS.

Hydrogen‐Bond‐Assisted Helical Folding of Propeller‐Shaped Molecules: Effects of Extended π‐Conjugation on Chiral Selection, Conformational Stability, and Exciton Coupling

AbstractCooperative interaction between multiple chiral centers dictates the absolute handedness of structural folding. We have designed and prepared a series of chiral C3‐symmetric tris(N‐salicylidenamine) derivatives that adopt three‐blade propeller‐like conformations. Synthetic access to an expanded family of such constructs was aided by enzymatic resolution and C–C cross‐coupling reactions of aryl‐substituted chiral propargylic alcohol derivatives. These key structural components were integrated into molecular propellers of predetermined helical screw sense. Through comparative studies on a homologous set of molecules, we found that installation of phenylene‐ethynylene‐derived π‐conjugation profoundly affected the stabilities of the helically folded structures, as evidenced by UV/Vis and circular dichroism (CD) studies. Increasing the number of hydrogen bonds through additional substitution also enhanced the populations of the folded conformations in solution. In addition to introducing steric bias to control structural folding, linearly π‐conjugated groups function as spatially well‐defined chromophores that give rise to characteristic exciton‐coupled circular dichroism. Absolute configurations of chiral centers could thus be further confirmed by comparing the torsional relationships between pairs of chromophores on adjacent subunits, which are fully consistent with the computationally predicted structural models.

Separation of racemic ortho-isobornylphenol into enantiomers and evaluation of their antioxidant activity

The resolution of the racemic ortho-isobornylphenol into enantiomers via diastereomeric camphanates was carried out. The absolute configuration ofchiral centers of synthesized compounds was established by the single crystal X-ray diffraction method. Antioxidant activity and membrane protective properties of individual enantiomers were studied on the model of H2O2-induced hemolysis of red blood cells.

Mixed Aromatic Acyloin Condensations with Recombinant Benzaldehyde Lyase: Synthesis of α‐Hydroxydihydrochalcones and Related α‐Hydroxy Ketones

AbstractRecombinant benzaldehyde lyase (BAL), expressed and purified from E. coli strain JM‐109, was used to catalyze the condensation of a series of methoxybenzaldehydes and phenylacetaldehyde in the synthesis of α‐(R)‐hydroxydihydrochalcones. Enantiomerically pure 1‐hydroxy‐1,3‐diphenylpropan‐2‐ones and o‐anisoin were also obtained as products of the BAL reaction. The R absolute configurations of chiral centers were determined by CD spectroscopy. α‐(R)‐Hydroxydihydrochalcones and 1‐hydroxy‐1,3‐diphenylpropan‐2‐ones are valuable synthons for chemoenzymatic syntheses of flavonoids. This is the first synthesis of α‐(R)‐hydroxydihydrochalcones by a microbial enzyme.

Optically active 2-cymantrenyloxazolines: synthesis and regioselective metallation

Three optically active oxazolines with a cymantrenyl substituent at position 2 of the heterocycle have been prepared. Metallation of these compounds withn-BuLi proceeds only at the two diastereotopic α- and α'-positions of the Cp-ring to an equal extent. The dependence of the sign of Cotton effect in the region of 300–350 nm upon the absolute configuration of chiral centers remote from the Cp-ring has been demonstrated.