Isomeric Alcohols Research Articles

Stereoselectivity of electroreduction of a menthone-isomenthone mixture

Electroreduction of an equilibrium menthone-isomenthone mixture at a controlled potential in a diaphragm cell on various cathodes was studied. The influence exerted by the nature of a solvent and of an electrode, electrode material, and various additives on the reduction stereoselectivity of ketones was examined. Conditions for a predominant formation of the most stable of the four isomeric alcohols being formed, menthol, were found.

Synthesis and Anti‐HIV‐1 Evaluation of New Sonogashira‐Modified Emivirine (MKC‐442) Analogues

AbstractThe MKC‐442 analogue 6‐(3,5‐dimethylbenzyl)‐5‐ethyluracil substituted with a (propargyloxo)methyl group at N(1) has previously been found highly active against HIV‐1. The CC bond in the substituent at N(1) is here utilized in a series of chemical reactions in order to develop new agents with higher activity against HIV‐1‐resistant mutants. The syntheses involved Pd‐catalyzed C,C‐coupling reactions, addition of disulfides, and click chemistry on the terminal CC bond as well as addition of bromine to the so formed internal CC bonds. Sonogashira coupling were performed with silyl‐derivatized iodobenzyl alcohols which, after deprotection, were oxidized to aldehydes by means of IBX. The isomeric alcohol 37 was obtained in the Sonogashira reaction of propargyl alcohol with the N(1)‐substituted (4‐iodobenzyloxy)methyl derivative of the above mentioned uracil. Compound 37 turned out to be the most effective compound against problematic HIV‐1 mutants. The general observation in the present work is that a combination of alkyne and aryl in the substituent at N(1) leads to highly active compounds against HIV‐1.

Total synthesis of vinblastine, vincristine, related natural products, and key structural analogues.

Full details of the development of a direct coupling of catharanthine with vindoline to provide vinblastine are described along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addition of the resulting reaction mixture to an Fe(III)-NaBH(4)/air solution leads to oxidation of the C15'-C20' double bond and reduction of the intermediate iminium ion directly providing vinblastine (40-43%) and leurosidine (20-23%), its naturally occurring C20' alcohol isomer. The yield of coupled products, which exclusively possess the natural C16' stereochemistry, approaches or exceeds 80% and the combined yield of the isomeric C20' alcohols is >60%. Preliminary studies of Fe(III)-NaBH(4)/air oxidation reaction illustrate a generalizable trisubstituted olefin scope, identify alternatives to O(2) trap at the oxidized carbon, provide a unique entry into C20' functionalized vinblastines, and afford initial insights into the observed C20' diastereoselectivity. The first disclosure of the use of exo-catharanthine proceeding through Delta(19',20')-anhydrovinblastine in such coupling reactions is also detailed with identical stereochemical consequences. Incorporating either a catharanthine N-methyl group or a vindoline N-formyl group precludes Fe(III)-promoted coupling, whereas the removal of the potentially key C16 methoxy group of vindoline does not adversely impact the coupling efficiency. Extension of these studies provided a total synthesis of vincristine (2) via N-desmethylvinblastine (36, also a natural product), 16-desmethoxyvinblastine (44) and 4-desacetoxy-16-desmethoxyvinblastine (47) both of which we can now suggest are likely natural products produced by C. roseus, desacetylvinblastine (62) and 4-desacetoxyvinblastine (59), as well as a series of key analogues bearing systematic modifications in the vindoline subunit. Their biological evaluation provided additional insights into the key functionality within the vindoline subunit contributing to the activity and sets the foundation on which further, more deep-seated changes in the structures of 1 and 2 will be explored in future studies.

Charge localization in alcohol isomers studied by Compton scattering

The isomers of small molecule alcohols propanol (PrOH) and butanol (BuOH) are studied by x-ray Compton scattering experiments with synchrotron radiation and density-functional theory calculations. The lineshape of the measured spectra, i.e., the Compton profile, is a momentum-space property, and its changes reflect changes in the electronic charge density between the isomers. Compared to the linear alcohols (n-PrOH and n-BuOH), the Compton profiles of the branched alcohols (iso-PrOH, iso-BuOH, sec-BuOH) are found to be narrower, which indicates a more delocalized charge for the latter. The calculations are performed for systems consisting of one to three monomer units and are found to reproduce reasonably the experimental spectral features. The influence of the basis set and exchange-correlation scheme is studied in more detail. The results provide new insight into the isomeric differences in small molecule alcohols and show that quantum chemical calculations can be increasingly tested against the x-ray Compton scattering data.

Characterization of O 2 ( 1Δ g)-Derived Oxidation Products of Tryptophan: A Combination of Tandem Mass Spectrometry Analyses and Isotopic Labeling Studies

The fragmentation mechanisms of singlet oxygen [O(2) ((1)Delta(g))]-derived oxidation products of tryptophan (W) were analyzed using collision-induced dissociation coupled with (18)O-isotopic labeling experiments and accurate mass measurements. The five identified oxidized products, namely two isomeric alcohols (trans and cis WOH), two isomeric hydroperoxides (trans and cis WOOH), and N-formylkynurenine (FMK), were shown to share some common fragment ions and losses of small neutral molecules. Conversely, each oxidation product has its own fragmentation mechanism and intermediates, which were confirmed by (18)O-labeling studies. Isomeric WOH lost mainly H(2)O + CO, while WOOH showed preferential elimination of C(2)H(5)NO(3) by two distinct mechanisms. Differences in the spatial arrangement of the two isomeric WOHs led to differences in the intensities of the fragment ions. The same behavior was also found for trans and cis WOOH. FMK was shown to dissociate by a diverse range of mechanisms, with the loss of ammonia the most favored route. MS/MS analyses, (18)O-labeling, and H(2)(18)O experiments demonstrated the ability of FMK to exchange its oxygen atoms with water. Moreover, this approach also revealed that the carbonyl group has more pronounced oxygen exchange ability compared with the formyl group. The understanding of fragmentation mechanisms involved in O(2) ((1)Delta(g))-mediated oxidation of W provides a useful step toward the structural characterization of oxidized peptides and proteins.

Fungal Biotransformation of (±)-Linalool

The biotransformation of (+/-)-linalool was investigated by screening 19 fungi. Product accumulation was enhanced by substrate feeding and, for the first time, lilac aldehydes and lilac alcohols were identified as fungal biotransformation byproduct using SPME-GC-MS headspace analysis. Aspergillus niger DSM 821, Botrytis cinerea 5901/02, and B. cinerea 02/FBII/2.1 produced different isomers of lilac aldehyde and lilac alcohol from linalool via 8-hydroxylinalool as postulated intermediate. Linalool oxides and 8-hydroxylinalool were the major products of fungal (+/-)-linalool biotransformations. Furanoid trans-(2 R,5 R)- and cis-(2 S,5 R)-linalool oxide as well as pyranoid trans-(2 R,5 S)- and cis-(2 S, 5 S)-linalool oxide were identified as the main stereoisomers with (3 S,6 S)-6,7-epoxylinalool and (3 R,6 S)-6,7-epoxylinalool as postulated key intermediates of fungal (+/-)-linalool oxyfunctionalization, respectively. With a conversion yield close to 100% and a productivity of 120 mg/L.day linalool oxides, Corynespora cassiicola DSM 62485 was identified as a novel highly stereoselective linalool transforming biocatalyst showing the highest productivity reported so far.

The functional divergence of short‐chain dehydrogenases involved in tropinone reduction

Tropane alkaloids typically occur in the Solanaceae and are also found in Cochlearia officinalis, a member of the Brassicaceae. Tropinone reductases are key enzymes of tropane alkaloid metabolism. Two different tropinone reductases form one stereoisomeric product each, either tropine for esterified alkaloids or pseudotropine that is converted to calystegines. A cDNA sequence with similarity to known tropinone reductases (TR) was cloned from C. officinalis. The protein was expressed in Escherichia coli, and found to catalyze the reduction of tropinone. The enzyme is a member of the short-chain dehydrogenase enzyme family and shows broad substrate specificity. Several synthetic ketones were accepted as substrates, with higher affinity and faster enzymatic turnover than observed for tropinone. C. officinalis TR produced both the isomeric alcohols tropine and pseudotropine from tropinone using NADPH + H(+) as co-substrate. Tropinone reductases of the Solanaceae, in contrast, are strictly stereospecific and form one tropane alcohol only. The Arabidopsis thaliana homologue of C. officinalis TR showed high sequence similarity, but did not reduce tropinone. A tyrosine residue was identified in the active site of C. officinalis TR that appeared responsible for binding and orientation of tropinone. Mutagenesis of the tyrosine residue yielded an active reductase, but with complete loss of TR activity. Thus C. officinalis TR presents an example of an enzyme with relaxed substrate specificity, like short-chain dehydrogenases, that provides favorable preconditions for the evolution of novel functions in biosynthetic sequences.

Effects of resonant phonon scattering from internal molecular modes on the thermal conductivity of molecular glasses

The thermal conductivity $\ensuremath{\kappa}(T)$ of the crystalline and glassy phases of the two isomers of propyl alcohol has been measured. The two isomers differ by a minor chemical detail involving the position of the hydroxyl group with respect to the carbon backbone. Such a difference in molecular structure leads, however, to disparate behaviors for the temperature dependence of $\ensuremath{\kappa}(T)$, for both glass and crystal states. The $\ensuremath{\kappa}(T)$ for the glass shows for 1-propanol an anomalously large plateau region comprising temperatures within $6--90\phantom{\rule{0.3em}{0ex}}\mathrm{K}$, while data for isomeric 2-propanol show only a small plateau up to $10\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ which is comparable to data on lower alcohols. The results emphasize the role played by internal molecular degrees of freedom as sources of strong resonant phonon scattering.

Direct coupling of catharanthine and vindoline to provide vinblastine: total synthesis of (+)- and ent-(-)-vinblastine.

A direct coupling of catharanthine with vindoline to provide vinblastine is detailed along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine amine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addition of the resulting reaction mixture to an Fe(III)−NaBH4/air solution leads to oxidation of the C15‘−C21‘ double bond and reduction of the intermediate iminium ion directly providing vinblastine (43%) and leurosidine (23%), its naturally occurring C21‘ alcohol isomer. The yield of coupled products, which exclusively possess the natural C16‘ stereochemistry, approaches or exceeds 80%, and the combined yield of the isomeric C21‘ alcohols is 66%.

Poisoning with 1-propanol and 2-propanol

1-Propanol and 2-propanol are isomers of an alcohol with three carbons. They are colorless liquids with a sweet odor. 1-Propanol is metabolized by alcohol dehydrogenase to propionic acid and presents with metabolic acidosis and elevated anion gap, whereas 2-propanol is metabolized by alcohol dehydrogenase to acetone and presents with rapidly developing (within 3-4 h after exposure) ketosis and ketonuria but without metabolic acidosis. We report a patient who simultaneously ingested a lethal dose of 1-propanol and 2-propanol as a hand disinfectant in hospital. The patient lost consciousness and stopped breathing within half an hour after ingestion. He was intubated and artificially ventilated. Initial laboratory results showed mixed acidosis with elevated anion gap, but ketonuria appeared only 12 h after admission and 6 h following the regaining of consciousness. Therefore, laboratory results in simultaneous poisoning with two isomers of alcohol are not just a sum of laboratory results obtained in isolated poisoning with each isomer because they influence each other's metabolism: 1-propanol retards the metabolism of 2-propanol to acetone. In conclusion, 1-propanol and 2-propanol poisoning presents early with mixed acidosis and elevated anion gap and only later with ketonuria.

Comparative study in the asymmetric bioreduction of ketones by plant organs and undifferentiated cells

Stereoselective reduction of prochiral ketones was studied by using both cell cultures and wild tissues of various endemic plant species. Dedifferentiated cell cultures of Baccharis crispa reduced regioselectively, with excellent stereocontrol, and in an anti-Prelog manner the methyl ketone moiety of a diketone, meanwhile Tessaria absinthioides cell cultures yielded the other antipode of the secondary alcohol with an optical purity higher than 98% ee. Therefore, it is possible to prepare the S and R isomers of a secondary alcohol by reduction of the corresponding prochiral ketone with these two biocatalysts. Moreover, significant differences in the reductive capacity of cell cultures and differentiated tissues of the same plant species were found. This fact allows improving the yields and optical purities and, even more interesting, obtaining the antipode of a secondary alcohol with the same plant species by using alternatively both biocatalytic systems.

Glycosidic juvenogens: Derivatives bearing α,β-unsaturated ester functionalities

A series of the protected alkyl glycosides 5a/ 5b– 12a/ 12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4′-(2″-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester ( 1a/ 1b– 4a/ 4b; racemic structures) and ( 1a– 4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs–Knorr reaction, and the products were obtained in 82–92% yields. Deprotection of the carbohydrate functionality of 5a/ 5b– 12a/ 12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/ 13b– 20a/ 20b (diastereoisomeric mixtures) and 13a– 20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82–93% yields. Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of the respective enantiomers 13b– 20b of the alkyl glycosides for their structure elucidation and 13C chemical shift assignment by 1H and 13C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/ 13b– 20a/ 20b were performed on the red firebug ( Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which results in liberation of the biologically active juvenoid in the insect organism.

Epimers of bicyclo[2.2.2]octan-2-ol derivatives with antiprotozoal activity

(2 SR,6 RS,7 RS)-4-Dialkylaminobicyclo[2.2.2]octan-2-ols and several of their esters have shown promising activity against the causative organisms for malaria and sleeping sickness. The base-catalyzed epimerization of the alcohols was carried out by different methods giving their (2 RS,6 RS,7 RS)-isomers. Best results were obtained by the consecutive use of potassium tert-butoxide and sodium. The isomeric alcohols were converted to selected esters. All new compounds were tested for their activity against Trypanosoma brucei rhodesiense (STIB 900) and a multiresistant strain of Plasmodium falciparum. The antitrypanosomal activity and the cytotoxicity were in general increased. The most active antitrypanosomal agents were the benzoate 8b and the 4-chlorobenzoate 9b of the 4-pyrrolidino series. The nicotinate 10a and the isonicotinate 11a showed the highest antiplasmodial activities.

Ag0 and Co0 nanocolloids as recyclable quasihomogeneous metal catalysts for the hydrogenation of α,β-unsaturated aldehydes to allylic alcohol fragrances

Polyvinylpyrrolidone-stabilized Ag 0 and Co 0 nanoclusters are successful quasihomogeneous catalysts for the chemoselective hydrogenation of α,β-unsaturated aldehydes to allylic alcohols. Particularly the Ag 0 nanosols emerged as a worthwhile alternative for Pt and Ru based catalysts. Amides proved to be superior to the conventional alcohol solvents and emerged as excellent solvents for the synthesis and application of the colloidal metal catalysts. Finally, recycling of the colloidal catalysts by solvent-resistent nanofiltration (SRNF) with custom-made polyimide membranes proved practicable and a satisfactory preservation of the catalysts’ nanodispersion and performance was observed. The hydrogenation of the α,β-unsaturated aldehydes cinnamaldehyde ( trans -3-phenyl-2-propenal), citral (3,7-dimethyl-2,6-octadienal) and leaf aldehyde ( trans -2-hexenal) was investigated with metal colloids as quasihomogeneous catalysts in organic solvents. Using polyvinylpyrrolidone-stabilized Ag 0 and Co 0 nanoclusters, the carbonyl compounds were chemoselectively hydrogenated to the desired allylic alcohol fragrances. Particularly the Ag 0 nanosols emerged as a worthwhile alternative for Pt or Ru based catalysts. Amides proved to be excellent solvents for the synthesis as well as for the application of the metal nanocolloids in the hydrogenation of α,β-unsaturated aldehydes. In the challenging hydrogenation of citral, a selectivity exceeding 70% towards the doubly unsaturated alcohol isomers (geraniol and nerol) was attained at 90% conversion using Ag 0 nanocolloids dispersed in N , N -dimethylacetamide. Reactions were performed under mild conditions (2.0 MPa H 2 , 323 K) at a molar citral/silver ratio of 200/1. The addition of Lewis acid cations, such as Fe 3+ or Zn 2+ resulted in a further improvement of the catalytic activity and chemoselectivity. Finally, by application of membrane filtrations, an efficient separation of the metallic nanocolloids from the reaction mixtures was realized. In the recycling of the metal nanosols, the metal catalysts’ nanodispersion and performance were satisfactorily preserved.

The Isolation and Identification of Volatile Insect Repellents from the Fruit of the Osage Orange (Maclura pomifera)

The fruit of the Osage orange tree, Maclura pomifera (Raf.) Schneid, was tested for repellency using the European house cricket, Gryllus domesticus (L.). After preliminary tests showed the fruit to possess repellent properties, two volatile components of the fruit were isolated and identified by GC/MS. The two isomeric alcohols, isoamyl alcohol and 2-methyl-2-butanol, were found to be repellent both in combination and individually.

Balancing Hydrophobic and Hydrophilic Forces at the Water/Vapor Interface: Surface Structure of Soluble Alcohol Monolayers

Surface tension and surface specific vibrational techniques were used to study the structure of soluble alcohol monolayers adsorbed to the air/water interface. Surface tension measurements were used to determine terminal monolayer coverages of different alcohol isomers whereas the surface specific vibrational sum frequency generation probed the interfacial structure and organization. The alcohols studied ranged from heptanols to dodecanols with constitutional isomers having the −OH group in the 1, 2, 3, and 5 positions. Not surprisingly, linear isomers form tightly packed monolayers having molecular areas of ∼20 Å2/molecule, a value close to the calculated cross section of linear, all-trans alkyl chains. The vibrational spectra of these monolayers consistently show features associated with monolayers having very little conformational disorder. For the 2- and 3-position isomers, surface tension measurements show surface coverages that were only half those of the linear isomers. Quantitative analyses of the vibrational band intensities in the CH stretching region show that methyl groups in the C1 and Cn positions contribute constructively to observed spectral intensities. Together with calculations of areas corresponding to different conformers, monolayers formed by these isomers are predicted to adopt structures with two gauche defects. Such structures require that the repulsive hydrophobic interactions of shorter alkyl segments with the water subphase be strong enough to offset the cohesive van der Waals interactions of the longer alkyl segments. Unlike the 2- and 3-position alcohols, 5-position isomers have surface areas and spectral band intensities that show a systematic variation over the range of alkyl chain lengths. Experiments are unable to quantitatively address the question of preferred conformer structures for these branched alcohols having pairs of longer alkyl segments. Nevertheless, the vibrational spectra of these 5-position alcohols suggest a complex organization of monomers adsorbed to the air/water interface.

A gas-chromatographic study of the adsorption of vapors of oxygen-containing compounds on fluorinated carbon

The adsorption of the vapors of a number of oxygen-containing compounds (alcohols, ketones, acids, and other functional derivatives of hydrocarbons) on fluorinated carbon (FC) was studied by the gas chromatography method at low surface coverages. The Henry law constants, heats of adsorption, standard entropies of adsorption, and retention indices were determined. An analysis of adsorption and IR-spectroscopy measurements suggests that FC contains no surface active sites capable of forming hydrogen bonds. It was established that the adsorption of oxygen-containing compounds on a FC surface is primarily governed by dispersion interactions. The adsorbent under study was found to exhibit a high selectivity in separation of isomeric alcohols.

Enantiopure (9‐Anthryl)(2‐piperidyl)‐ and (9‐Anthryl)(2‐pyridyl)methanols – Their Use as Chiral Modifiers for Heterogeneous Hydrogenation of Keto Esters over Pt/Al2O3

AbstractA route toward the synthesis of the erythro isomer of (9‐anthryl)(2‐piperidyl)methanol is presented as well as resolution and assignment of the structure (through NMR). The use of both the erythro and threo enantiopure isomers of this new amino alcohol, and its precursor [(9‐anthryl)(2‐pyridyl)methanol], as chiral modifiers for the Pt/Al2O3 hydrogenation of ethyl lactate showed that the erythro isomer is not necessarily the most efficient chiral modifier. This is probably because of the 9‐anthryl group. The enantioselectivities that this compound provides are not, as one would expect, higher than those observed with the naphthyl group.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Identification of Components of Commercial Alkylsalicylaldoxime Based Reagents by GC–MS

A simple gas chromatographic-mass spectrometric (GC–MS) method for the identification of components present in alkylsalicylaldoximes based metal extractants LIX860, LIX622, LIX622N, Acorga PT5050 and Acorga P5100 is described. These reagents have been developed for removing copper in hydrometallurgical processes. The extractants were analyzed by GC–MS in the Full Scan mode without any derivatization step. 5-Nonylsalicylaldoxime in the extractants LIX622N, Acorga PT5050 and Acorga P5100 and 5-dodecylsalicylaldoxime in the extractants LIX622 and LIX860 were found to be present as a mixture of alkyl isomeric compounds. The extractant Acorga P5100 also contains a large amount of p-nonylphenol isomers whereas LIX622, LIX622N and Acorga PT5050 contain tridecyl alcohol isomers. In addition, the presence of small amounts of alkylphenol isomers was detected in all LIX reagents. The GC–MS study has revealed that the major fragmentation ions of the alkylsalicylaldoximes can be classified into two types: the molecular ion less CnH2n+1 and the molecular ion less CnH2n+1 and water. Cleavage of the benzylic bond predominates, resulting in the base peak. The identified compounds have been classified in different types that show different base peaks and the possible structures of the alkyl groups based on the substitution of the alpha-carbon are proposed.

Aroma composition and new chemical markers of Spanish citrus honeys

Sixty six volatile compounds were detected in Spanish citrus honeys by GC–MS. Certain compounds appeared to be characteristic of this floral source, particularly high concentrations of terpenes and derivatives, such as linalool, ( Z) ( E)-linalool oxide, α-terpineol, terpineal and isomers of lilac aldehyde and lilac alcohol. Sinensal isomers are also proposed as new chemical markers for citrus honeys, since these compounds are present only in this floral source. OAV values suggested that these compounds contributed strongly to the characteristic aroma of citrus honeys.