Ratio Of Regioisomers Research Articles

Lipidomic analysis of the extremophilic red alga Galdieria sulphuraria in response to changes in pH

Analysis of polar lipids from the red micro-alga Galdieria sulphuraria by means of the HILIC-LC/high resolution ESI-tandem MS determined 14 classes of lipids including identification of tens of molecular species of lipids and their regioisomers. The extremophilic alga G. sulphuraria uses several mechanisms for adaptation to low pH and high temperature, the major change being a replacement of cellular phospholipids by betaine lipids. We also found a change in the ratio of regioisomers of the polar lipids, i.e. phospho-, glyco- and betaine lipids, in dependence on the culture medium pH. We hypothesize that biosynthesis of polar lipids via the prokaryotic and/or eukaryotic pathway is dependent on ambient pH.

Prediction by (13)C NMR of regioselectivity in 1,3-dipolar cycloadditions of acridin-9-yl dipolarophiles.

Strong correlation was found between (13)C NMR chemical shifts of dipolarophilic CH=CH carbons and regioselectivity in 1,3-dipolar cycloadditions of new acridin-9-yl dipolarophiles with stable benzonitrile oxides (BNO). Accordingly, two starting dipolarophiles, (acridin-9-yl)-CH=CH-R (R = COOCH3 or Ph), reacted with three BNOs (2,4,6-trimethoxy, 2,4,6-trimethyl, and 2,6-dichloro) to give a mixture of two target isoxazoline regioisomers in which the acridine was bound either to isoxazoline C-4 carbon (4-Acr) or C-5 one (5-Acr). Methyl 3-(acridin-9-yl)propenoate afforded major 4-(acridin-9-yl)-isoxazoline-5-carboxylates (4-Acr) and minor 5-(acridin-9-yl)-4-carboxylates (5-Acr). 9-(2-Styryl)acridine regiospecifically afforded only 4-Acr cycloadducts. The ratios of regioisomers were compared with analogous reactions of acridin-4-yl dipolarophiles. Regioselectivity was dependent on a polarity of the CH=CH bond, donor effects in BNO, and stabilization by stacking of aromatic substituents in the products.

Phase‐Transfer‐Catalyzed Asymmetric Synthesis of Chiral N‐Substituted Pyr­azoles by Aza‐Michael Reaction

AbstractAn efficient cinchona‐based phase‐transfer‐catalyzed asymmetric aza‐Michael reaction of pyrazole with various α,β‐unsaturated ketones has been developed for the preparation of chiral N‐substituted pyrazoles. This reaction provided the desired products in good yields (up to 99 %) with excellent enantioselectivities (87–94 % ee). In addition, the reaction of 3‐methyl‐1H‐pyrazole, an unsymmetrically substituted pyrazole, was treated with α,β‐unsaturated ketones to afford the corresponding chiral N‐substituted pyrazoles in good yields (up to 99 %) with excellent enantioselectivities (90–92 % ee) and regioisomeric ratios of up to 9:1.

ChemInform Abstract: The ′Mikami′‐Catalyst in Enantioselective Diels—Alder Reactions of Juglone‐Based Dienophiles with Different 1‐Oxygenated Dienes: An Investigation on the Substitution Pattern Dependent Regioselectivity.

AbstractThe enantioselective reactions are not driven to completion, but stopped in order to determine the regioisomeric ratios and enantiomeric excesses of the products.

Influence of the -CH2X substituent on the regioselectivity of intramolecular meta-photocycloaddition reactions.

In studies related to the synthesis of the bicyclo[3.2.1]octane core of enterocin by an intramolecular meta-photocycloaddition, it was found that the regioselectivity of the reaction depends strongly on the substituent -CH2X in the ortho-position to the tether. Electropositive groups X (X = H, Me, TMS, TES) gave preferentially the linear isomer (regioisomeric ratio = 87/13 to >95/5), whereas electronegative substituents (X = OH, OAc, F) showed a clear preference for the angular isomer (regioisomeric ratio = 75/25 to >95/5). The silylated and fluorinated products were obtained as single isomers in moderate yield.

Temperature dependence of production of structured triacylglycerols in the alga Trachydiscus minutus

This study describes the identification of regioisomers and enantiomers of triacylglycerols of C20 polyunsaturated fatty acids (PUFAs) in the alga Trachydiscus minutus cultivated at different temperatures using reversed- and chiral-phase liquid chromatography–mass spectrometry. The use of the two different phases contributes to ready identification, both qualitative and semiquantitative, of regioisomers and enantiomers of triacylglycerols containing eicosapentaenoic and arachidonic in the molecule. The ratio of regioisomers and enantiomers of triacylglycerols (TAG) depends on the temperature of cultivation; with lowering temperature the proportion of the achiral TAG increases and the enantiomer ratio diverges from 1:1.

Nanosheet-Enhanced Rhodium(III)-Catalysis in C–H Activation

Rhodium(III)-catalyzed C–H activation has been promoted impressively with ligand-attached nanosheets of layered double hydroxides (LDHs), a natural and/or synthetic anionic layered compound. A yield of >99% and a regioisomeric ratio of >20:1 have been produced in the coupling of alkenes with N-(pivaloyloxy)benzamide. The nanosheets have been revealed to enhance the catalytic activity by affording the desired basicity and improve the regioselectivity by serving as the rigid substitution of α-amino acid ligands.

Copper(I)-catalyzed regioselective addition of nucleophilic silicon across terminal and internal carbon-carbon triple bonds.

The copper(I) alkoxide-catalyzed release of a silicon-based cuprate reagent from a silicon-boron pronucleophile is applied to the addition across carbon-carbon triple bonds. Commercially available CuBr⋅Me2S was found to be a general precatalyst that secures high regiocontrol for both aryl- and alkyl-substituted terminal as well as internal alkynes. The solvent greatly influences the regioisomeric ratio, favoring the linear regioisomer with terminal acceptors. This facile protocol even allows for the transformation of internal acceptors with remarkable levels of regio- and diastereocontrol.

Comparative analysis of triacylglycerols from different Stichococcus strains by RP-HPLC/APCI-MS and chiral HPLC

The main analytical benefit of this study is the development of methods enabling a rapid determination of triacylglycerols (TAGs) in different strains of the green alga Stichococcus bacillaris and detailed identification and quan- tification of a complex mixture of natural TAGs by reversed phase liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (RP-HPLC/APCI-MS) and chi- ral HPLC. Neutral ion scan can readily identify, both qualita- tively and semiquantitatively, triacylglycerols containing 16:2 and16:3fattyacids(FAs)inthemolecule.Sincemoredetailed studies in this respect have been stymied by the shortage of 16:2 and 16:3 FAs, we decided to study the alga Stichococcus as a potential new biotechnological source of C16 polyunsat- urated fatty acids (PUFAs). We conclude that the genus Stichococcus is a major producer of C16 PUFAs mostly contained in TAGs. Further, the ratio of regioisomers and enantiomers of TAGs depends on the content of fatty acids; with lowering temperature, the proportion of the achiral TAG increases, and so does the enantiomer ratio from 1:1. Dienoic FAs preferentially esterify position sn-3, whereas in trienoic acids, it is position sn-1.

Regioselectivity of Larock Heteroannulation: A Contribution from Electronic Properties of Diarylacetylenes

A series of 2,3-diarylindoles were synthesized from 2-iodoaniline and unsymmetrical diarylacetylenes using the Larock heteroannulation. Diarylacetylenes bearing electron-withdrawing substituents lead to 2,3-diarylindoles with substituted phenyl moieties at the 2-position as major products, while those with electron-donating groups preferably yield indole products with substituted phenyl moieties at the 3-position. The regioisomeric product ratios exhibit a clear correlation with Hammett σ(p) values. DFT calculations reveal the origin of this effect, displaying smaller activation energy barriers for those pathways leading to the major regioisomer.

2‐Aminobenzaldehydes as Versatile Substrates for Rhodium‐Catalyzed Alkyne Hydroacylation: Application to Dihydroquinolone Synthesis

2‐Aminobenzaldehydes as Versatile Substrates for Rhodium‐Catalyzed Alkyne Hydroacylation: Application to Dihydroquinolone Synthesis

Phosphine-free thiopseudourea-Pd(II) complex catalyzed Larock heteroannulation of 2-haloamines with internal alkynes

We examined the Pd-catalyzed heteroannulation of 2-haloamines with internal alkynes under phosphine-free conditions. The thiopseudourea palladium(II) complex (5) found to be an efficient catalyst for the Pd induced heteroannulation. Achieved high turnover number for the heteroannulation reactions of internal alkynes with 2-iodoaniline. A variety of 2-bromoanilines and N-tosyl substituted 2-bromoanilines effectively reacted with different substituted internal alkynes to give the corresponding indoles in good to high yields (1:1 ratio of regioisomers).

Cloning, overexpression and biocatalytic exploration of a novel Baeyer-Villiger monooxygenase from Aspergillus fumigatus Af293

The presence of several putative Baeyer-Villiger Monooxygenases (BVMOs) encoding genes in Aspergillus fumigatus Af293 was demonstrated for the first time. One of the identified BVMO-encoding genes was cloned and successfully overexpressed fused to the cofactor regenerating enzyme phosphite dehydrogenase (PTDH). The enzyme named BVMOAf1 was extensively characterized in terms of its substrate scope and essential kinetic features. It showed high chemo-, regio- and stereoselectivity not only in the oxidation of asymmetric sulfides, (S)-sulfoxides were obtained with 99% ee, but also in the kinetic resolution of bicyclo[3.2.0]hept-2-en-6-one. This kinetic resolution process led to the production of (1S,5R) normal lactone and (1R,5S) abnormal lactone with a regioisomeric ratio of 1:1 and 99% ee each. Besides, different reaction conditions, such as pH, temperature and the presence of organic solvents, have been tested, revealing that BVMOAf1 is a relatively robust biocatalyst.

A ring-closing metathesis approach to eight-membered benzannelated scaffolds and subsequent internal alkene isomerizations

A set of eight-membered benzannelated heterocycles containing two heteroatoms (O,O, NR,NR and O,NR where R=protecting group) was synthesized by ring-closing metathesis from the corresponding ortho-bis-allyl precursors. In this manner, 7-methoxy-2,5-dihydro-1,6-benzodioxocine, 1,2,5,6-tetrahydro-1,6-benzodiazocines, 5,6-dihydro-2H-1,6-benzoxazocines and 5,6,9,10-tetrahydropyrido[2,3-b][1,4]diazocine were synthesized. A number of these compounds were then treated with the catalyst [RuClH(CO)(PPh3)3] to facilitate isomerization of the alkene into conjugation with the heteroatoms in the eight-membered ring. Quite surprisingly, an equal ratio of regioisomers was obtained, even if the heteroatoms were different.

Regiochemistry of the Condensation of 2-Aroyl-cyclohexanones and 2-Cyanoacetamide: 13C-Labeling Studies and Semiempirical MO Calculations

Hydroxy-aryl-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles represent interesting chemical scaffolds, but synthetic access to these compounds is limited. The reaction of 2-aroyl-cyclohexanones with 2-cyanoacetamide and base in ethanol has been reported to lead to the formation of the tetrahydroisoquinoline isomer. We show that depending on the electronic nature of the para-substituent on the aryl ring, formation of the regioisomeric tetrahydroquinoline isomer can significantly compete. The electron-donating or -withdrawing properties of the para-substituent of the aryl ring determines the ratio of product isomers. A series of 2-aroyl-cyclohexanones, with para-substituents ranging from electron-donating to electron-withdrawing, were reacted with [2-(13)C]-cyanoacetamide. The product ratio and absolute regiochemistry were directly determined by quantitative (13)C, HMBC, and NOESY NMR spectroscopy on the reaction mixtures. A clear relationship between the regioisomeric product ratio and the Hammett sigma values of the substituents is demonstrated. This is explained by the separate in situ yields, which reveal that the pathway leading to the tetrahydroquinoline regioisomer is significantly more sensitive toward the electronic nature of the para-substituent than the pathway leading to the tetrahydroisoquinoline. Semiempirical AM1 molecular orbital calculations on the starting electrophile 2-aroyl-cyclohexanone support a correlation between the energy of the LUMOs and the regioisomeric product ratio. Our results facilitate synthetic access to a range of these interesting synthetic intermediates.

Synthesis of trans‐Disubstituted Alkenes by Cobalt‐Catalyzed Reductive Coupling of Terminal Alkynes with Activated Alkenes

A cobalt-catalyzed reductive coupling of terminal alkynes, RC≡CH, with activated alkenes, R'CH=CH(2), in the presence of zinc and water to give functionalized trans-disubstituted alkenes, RCH=CHCH(2)CH(2)R', is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl(2)/P(OMe)(3)/Zn catalyst system to afford 1,2-trans-disubstituted alkenes with high regio- and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl(2)/P(OPh)(3)/Zn system providing a mixture of 1,2-trans- and 1,1-disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3-enynes and acetylene gas with alkenes. Furthermore, a phosphine-free cobalt-catalyzed reductive coupling of terminal alkynes with enones, affording 1,2-trans-disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air-stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed.

Ratios of Regioisomers of Minor Acylglycerols Less Polar than Triricinolein in Castor Oil Estimated by Mass Spectrometry

AbstractWe have recently reported the identification of forty new minor molecular species of acylglycerols containing hydroxy fatty acids less polar than triricinolein by electrospray ionization mass spectrometry of the lithium adducts. The ratios of regioisomers of triacylglycerols (ABC and AAB types) and tetraacylglycerols (AAAB type) identified were estimated by the relative abundances of the fragment ions from the neutral losses of fatty acids as α,β‐unsaturated fatty acids at the sn‐2 position. The order of the contents of regioisomers of triacylglycerols with the fatty acids at the sn‐2 position are: nonhydroxy fatty acids > monohydroxy fatty acids > dihydroxy fatty acids > trihydroxy fatty acids. For tetraacylglycerols (AAAB type) such as ricinoleoylricinoleoyl–ricinoleoyl–oleoyl–glycerol (RRRO), ricinoleoylricinoleoyl chain was predominately at the sn‐2 position, while ricinoleate was not detected at the sn‐2 position.

Curtin–Hammett and Steric Effects in HOBt Acylation Regiochemistry

While hydroxybenzotriazole is commonly used in a variety of bond-forming reactions, its acylation has been shown to produce a regiochemical (O vs N) mixture with complex kinetic behavior. Increased steric bulk on the electrophile favors formation of the oxygen-acylated product. Upon standing as a solid, the mixture can isomerize completely to the nitrogen adduct. An equilibrium ratio of regioisomers can be re-established in solution by adding either nucleophilic or electrophilic reagents, suggesting that the composition of the mixture is not significant to subsequent reactivity. Solvents can affect this regiochemical equilibrium through a Curtin-Hammett effect, where the shift in the tautomeric equilibrium of HOBt in polar solvents biases the reaction toward the oxygen adduct.

Potassium tert-Butoxide Promoted Intramolecular Arylation via a Radical Pathway

Potassium tert-butoxide mediated intramolecular cyclization of aryl ethers, amines, and amides was efficiently performed under microwave irradiation to provide the corresponding products in high regioisomeric ratios. The reaction proceeds via single-electron transfer to initiate the formation of an aryl radical, followed by a kinetically favored 5-exo-trig and subsequent ring expansion.

Polar co-solvents in tertiary alcohols effect initial reaction rates and regio-isomeric ratio ranging from 1.2 to 2.2 in a lipase catalysed synthesis of 6- O- and 6′- O-stearoyl sucrose

The effect of polar, aprotic solvents in tertiary alcohols on the regio-selectivity in a Candida antarctica lipase B catalysed synthesis of sucrose stearate was investigated. The solubility of sucrose, initial formation velocities and final concentrations of 6- O- and 6′- O-stearoyl sucrose were affected by addition of polar co-solvents. Without co-solvents 6- O-stearoyl sucrose appeared as the first product followed by 6′- O-stearoyl sucrose. In the presence of polar co-solvents both regio-isomers were synthesized from the beginning of the reaction. The highest initial formation velocities of 6- O- and 6′- O-stearoyl sucrose were 26 nmol min −1 and 17 nmol min −1, respectively, with a sucrose conversion of 86.7% obtained with 45% pyridine in 2-methyl-2-butanol. In the corresponding reaction medium with 2-methyl-2-propanol as tertiary alcohol a sucrose conversion of 86.3% was achieved. In the tertiary alcohols studied the overall regio-selectivity gradually decreased by adding polar co-solvent in the following order: no co-solvent > 45% pyridine ≥ 55% pyridine > 20% DMSO. Thus the regio-isomeric distribution expressing the steady state molar ratio of the 6- O-regio-isomer to the 6′- O-regio-isomer changed from 2:1 in absence of co-solvent to 1:1 in presence of DMSO. This change could be explained kinetically by the ratio between the initial formation velocities of the two regio-isomers, defined as the regio-isomeric ratio ( R = v 0 6 - O - / v 0 6 ′ - O - ) , which changed from R = 2.2 in absence of co-solvent to R = 1.2 in presence of DMSO.