bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic hydrolysis and esterification. Routes to optically pure cyclopentanols
Authors: Seemayer R. , Schneider M. P.
Published: September 2010

Using an esterhydrolase from Pseudomonas sp. (SAM II), a series of optically pure cyclopentanols 1‐4 was prepared by enzymatic hydrolysis of their corresponding acetates. Using the same enzyme, these cyclopentanols were esterified by enol esters as acyl donors. Due to identical stereochemical recognition in both reaction modes, opposite pairs of enantiomeres were obtained.
(Bio)dimerisation of unsaturated fatty acids
Authors: Colja N. , Laane M. , Cross Graham A. , Beindorff Chriiaan , Klooerman Jan , Haase K. Dieter
Published: September 2010

A comparison has been made between an enzymatic and a chemical route to dimeric fatty acids, using (poly)unsaturated fatty acids as starting material, with respect to mechanism, types of structures generated, yield, and costs. For bioconversion, the enzyme lipoxygenase extracted from soya‐bean pellets was used, whereas for the chemical process the clay‐catalysed route was followed. The enzymatic dimerisation proceeds via a radical mechanism and is more selective, but less co effective and productive than the clay‐catalysed reaction in which carbenium ions are involved.
Chemo‐enzymatic synthesis of rosmarinic acid
Authors: Pabsch K. , Rao N. N. , Wandrey C. , Petersen M. , Alfermann A. W.
Published: September 2010

(R)‐(+)‐3‐(3,4‐Dihydroxyphenyl)lactic acid was produced in an enzyme membrane reactor with an optical purity higher than 99%. Complete reactor modelling of the process was done and the theoretically evaluated data was verified by a continuous experiment with space‐time yields more than 1000g/(l·d).

For the synthesis of CoA‐activated caffeic acid, a new method was found to prepare the ester via the caffeic acid imidazolide.

In a batch experiment, it was shown that enzymatically prepared (R)‐(+)‐3‐(3,4‐dihydroxyphenyl)‐lactic acid and chemically synthesized CoA caffeic ester were converted to rosmarinic acid by an enzyme isolated from Coleus blumei cell cultures.
Plasmid‐based, D‐aminopeptidase‐catalysed synthesis of (R)‐amino acids
Authors: Asano Yasuhisa , Kishino Katsuhiko , Yamada Akiko , Hanamoto Sawako , Kondo Kiyosi
Published: September 2010

The gene for D‐aminopeptidase from Ochrobactrum anthropi SCRC Cl‐38 was cloned in Escherichia coli JM109. An expression plasmid pCl38DP (4.5 kb) was constructed. The amount of the enzyme in a cell‐free extract of E. coli JM109/pCl38DP was elevated up to 288000 units/liter culture, which is about 3600‐fold over that of O. anthropi SCRC Cl‐38. It was calculated that the enzyme comprised about 30% of the total extractable cellular protein. The intact cells of the E. coli transformant were used as a catalyst for (R)‐stereospecific hydrolysis of several racemic amino amides HCl. Complete hydrolysis of (R)‐alanine amide was achieved in a short time (4½h) from 5.0M racemic alanine amide HCl using cells of the E. coli transformant. The concentration of (R)‐alanine reached 220 g/l. The cells or the cell‐free extract catalyzed the synthesis of (R)‐2‐aminobutyric acid, (R)‐methionine, (R)‐norvaline and (R)‐norleucine from their amides in a similar manner.
Enzymes in reversed micelles: 4. Theoretical analysis of a one‐substrate/one‐product conversion and suggestions for efficient application
Authors: Verhaert Raymond M. D. , Hilhor Riet
Published: September 2010

A detailed analysis of the conversion of polar and apolar substrates in an heterogeneous medium is given. The enzyme is assumed to follow the mechanism: E + S⇌ES⇌E + P. The effects of various parameters, both enzymic and those of the microemulsion, are presented. In an extension to the model presented earlier, analysis of this simplified case reveals why a large difference is observed between the Km in aqueous solution and its value in microemulsions, suggesting increased affinity of the enzyme for a hydrophilic substrate and decreased affinity for an apolar substrate. It also demonstrates why, in contrast to studies in aqueous solutions, the rate constant of the reverse reaction (k‐2) affects the initial rate of the reaction in microemulsions. Furthermore, it is explained that the bell‐shaped relationship between the initial reaction rate and the water content of the microemulsion can depend on the value of the rate constant of the reverse reaction and on the relationship between the radius of the micelle and the molar ratio of detergent to water (w0) in the system. The model presented here predicts that bell‐shaped curves will only be observed in the conversion of substrates which are, at lea partially, confined to the water pool of the microemulsion. In order to illustrate the dependence of the rate of the reaction on the composition of the microemulsion, the example of δ‐chymotrypsin was chosen. Using this example, the effects of micellar parameters not accessible to systematic experimental variation can be calculated. The results of this analysis show that detailed knowledge of both microemulsion and enzymic parameters is necessary for an adequate description of the reaction rate. Based on the results of this analysis, advice to optimize the enzymatic conversion of both hydrophilic and hydrophobic substrates in heterogenic media is presented.
Enantioselective enzymatic catalysis.:1. A novel method to determine the enantiomeric ratio
Authors: Jongejan Jaap A. , Tol J. Bert , van Tol A , Geerlof Arie , Duine Johannis A.
Published: September 2010

The enantioselective properties of a large number of enzymes are conveniently characterized by the enantiomeric ratio, E = (kcat/KM)s/(kcat/KM)R. Chen and coworkers [Chen et al., J. Am. Chem. Soc. 104, 7294‐9 (1982)] have shown that the value of E can be obtained by measuring the enantiomeric excess, ee, as a function of the degree of conversion, ξ, in kinetic resolutions of a racemic substrate.

We noticed that determination of E from ee = f(E, ξ) is not practical when: (a) low amounts of enzyme or substrate are available; (b) analytical procedures for the determination of ee values of substrates or products are cumbersome or inaccurate; (c) complications arise from maturation of reaction mixtures. Direct evaluation of E from the kinetic parameters, on the other hand, requires both enantiomers to be available in enantiomerically pure form.

We show that the initial reaction rates for mixtures of enantiomers at fixed substrate concentration under otherwise identical conditions, are related by:

(vs, vR and vx represent the initial reaction rate of homochiral S‐enantiomer, homochiral R‐enantiomer and mixtures with (molar) fraction x of S‐enantiomer, respectively). Analytical procedures for the determination of E, vs and vR by this approach are presented. The merits are demonstrated for the lipase‐catalysed kinetic resolution of racemic glycidol ester and for the resolution of racemic alcohols by a quinoprotein dehydrogenase and an NAD‐dependent dehydrogenase.
Enantioselective enzymatic catalysis.:2. Applicability of methods for enantiomeric ratio determinations
Authors: Bert J. , van Tol A. , Jongejan Jaap A. , Geerlof Arie , Duine Johannis A.
Published: September 2010

Three methods for the determination of the enantiomeric ratio, E, of enantioselective, Michaelis‐Menten‐type enzymes have been investigated with respect to accuracy, using the method of propagation of standard deviation. In addition, estimations of standard deviations of E were obtained from simulations and representative experiments. The coefficient of variation (γE) achieved in the values derived from the kinetic parameters of the enantiomers (method I) does not depend on the absolute value of E. With initial‐rate measurements on mixtures of enantiomers at a fixed concentration of substrates (method II), the accuracy depends on the characteristics of the system, i.e., kinetic parameters, concentration and enantiomeric purity of the substrates, whereas with end‐point analysis (method III) the value of E is the crucial factor. Accurate estimates (γE< 0.1) of E can be obtained with method I, and for E < 30 also with method III.

As well as the aspect of accuracy, the methods have different intrinsic merits which can also be relevant in making a choice: method I gives information on the reaction mechanism; method II is well suited for screening purposes; method III is attractive for applied studies as it mimics a preparative process. In view of these complementary capabilities, an adequate set of tools seems to be available now for fundamental and applied studies on enantioselectivity.
Conversion of D‐ribo‐3‐hexosulose into D‐ribulose and D‐erythronic acid in aqueous medium
Authors: de Wit D. , van Rantwijk F. , Maat L. , Kieboom A. P. G.
Published: September 2010

The decomposition of D‐ribo‐3‐hexosulose in water, studied by HPLC, gave D‐ribulose (60‐65%) and D‐erythronic acid (20%), both isolated by column chromatography. D‐Ribulose was characterized using LC‐MS and NMR. From the latter technique, the ratio of three isomeric structures was determined. D‐Erythronic acid was characterized by NMR.
Hydride transfer reactions of benzylic alcohols catalyzed by acid faujasites
Authors: Climent María J. , Corma Avelino , García Hermenegildo , Iborra Sara , Primo Jaime
Published: September 2010

Reaction of five benzylic alcohols in solution at 78°C has been performed in the presence of a series of HY zeolites at three different levels of Na+ ‐to‐NH4+ exchange (HY‐21, HY‐50 and HY‐100) and framework Si‐to‐Al ratio (HY‐100, HY‐200 and HY‐400). Dehydration to form a CC double bond is the main primary process for 1‐phenyl‐ and 1,1‐diphenylethanol. Nevertheless, the initial alkenes are unstable, giving rise to the corresponding phenylethanes and, in the case of styrene, also to dimers. In contrast, benzyl alcohol and diphenylmethanol gave equimolar amounts of phenylmethanes and phenyl ketones, by an intermolecular hydride transfer not observed under conventional homogeneous acid catalysis. This process was found to be highly demanding from the point of view of the acid strength of the sites involved. Finally, triphenylmethanol showed a remarkable reluctance to undergo any change, although small amounts of triphenylmethane, benzophenone and 9‐phenyl‐9‐hydroxyfluorene were detected after long reaction times.
Calix (aza‐)crowns as potential ionophores for divalent and trivalent cations
Authors: Ostaszewski Ryszard , Stevens Tieme W. , Verboom Willem , Reinhoudt David N. , Kaspersen Frans M.
Published: September 2010

A series of calix (aza‐)crowns 6a‐f and 11a,b has been prepared by reaction of either calix dimethyl ester 4 or calix diacid dichloride 10 with an appropriate diamine. The complexation with both di‐ and trivalent cations has been qualitatively studied using fast‐atom bombardment mass spectrometry.
The first successful copper(I)‐catalysed alkoxydehalogenation of non‐activated aryl chlorides
Authors: Keegstra Menno A. , Brandsma Lambert
Published: September 2010

A study of the stability of the copper catalyst has led to the first successful copper(I) catalysed alkoxydehalogenation of non‐activated aryl chlorides.
Mechanism of the reaction of carbodiimides with carboxylic acids
Authors: Schotman A. H. M.
Published: September 2010

The kinetic parameters of the reaction of diphenylcarbodiimide with various carboxylic acids have been determined at a temperature interval of 20‐160°C.

The classical scheme for the reaction of carbodiimides with carboxylic acids is extended. It has been found that, at high temperatures, amides and isocyanates are the end products of the reactions. N‐Acylureas, initially formed from aromatic carbodiimides and carboxylic acids, dissociate into isocyanates and amides at temperatures above 60°C. N‐Acylureas formed by the reaction of carboxylic acids with aliphatic carbodiimides prove to be more stable: their dissociation temperature is about 50°C higher. Both the formation and dissociation of N‐acylureas are much faster when the parent acid is stronger.
Chemistry of indoles carrying basic functions. I. Transformation of hydroxyindolones into indoles
Authors: Moldvai István , Gács‐Baitz Eszter , Szántay Csaba
Published: September 2010

3‐Hydroxy‐3‐[(2‐ and 4‐pyridyl)methyl]‐1H‐indol‐2‐ones (1, 12) have been reduced with NaBH4/MeOH/t‐BuOH. After acidic treatment, 2‐ and 3‐substituted indoles (2, 11 and 13, 14, respectively) were obtained. The intermediates 3 and 4 of the rearrangement were isolated and the effect of the pyridylmethyl groups on the rearrangement has also been established.
The preparation and reactions of 2‐halogenoethyl β‐L‐arabinopyranosides
Authors: Hough Leslie , McCarthy Karl C. , Richardson Anthony C.
Published: September 2010

Acid‐catalysed reaction of L‐arabinose with 2‐chloroethanol, 2‐bromoethanol or 2‐iodoethanol at 50‐60 °C, afforded the highly crystalline 2‐haloethyl β‐L‐arabinopyranosides in 20%, 86% and 23% yields respectively, which each crystallised out directly from the reaction mixtures. Following O‐acetylation of 2‐bromoethyl β‐L‐arabinopyranoside, the bromo substituent underwent substitution by various nucleophilic anions (N3−, NCS−, AcS−, BzO−) to give the appropriate acetylated functionalised glycosides. O,S‐Deacetylation of 2‐(acetylthio)ethyl 2,3,4‐tri‐O‐acetyl‐β‐L‐arabinoside afforded 2‐mercaptoethyl β‐L‐arabinopyranoside, but deblocking of the 2‐thiocyanatoethyl 2,3,4‐tri‐O‐acetyl‐P‐L‐arabinoside in the same way afforded the thiol as a minor product, with the derived disulphide and methylthio derivatives as the major products. The origin of these compounds is discussed. Reaction of the 2‐bromoethyl arabinoside with base afforded the as‐fused bicycle 1,2‐O‐ethylene‐β‐L‐arabinopyranose in high yield. Acetonation and subsequent oxidation of the 2‐azidoethyl arabinoside gave the 2‐ketone, reductive amination of which led to the trans‐fused bicycle 2‐amino‐2‐deoxy‐1,2‐O, N‐ethylene‐β‐L‐ribose. Chlorination of 2‐chloroethyl β‐L‐arabinopyranoside with triphenylphosphine/carbon‐tetrachloride, followed by treatment with base afforded 3,4‐anhydro‐1,2‐O‐ethylene‐β‐L‐arabinopyranoside, ring‐opening of which by azide proceeded regiospecifically to give the 4‐azido‐D‐xylo isomer, which was reduced to the amine.
Gas‐phase pyrolysis of coumaran and 2,3‐dimethylcoumaran
Authors: van Meurs Marcel , Arends Isabel W. C. E. , Louw Robert , Mulder Peter
Published: September 2010

Pyrolysis of coumaran, 2,3‐dihydrobenzofuran,(Ia) at ca. 700°C leads to the isomeric o‐vinylphenol Ila and some benzofuran IIIa. The 2,3‐dimethyl derivative Ib ‘directly’ gives IIIa in a relatively easy double homolytic de‐methylation reaction (2).
Recent developments in polymer synthesis
Authors: Mijs W. J. , Addink R.
Published: September 2010

Recent developments in polymer synthesis are reviewed, especially those methods that lead to well defined structures: group‐transfer polymerization, living cationic and anionic polymerization from cyclic and acyclic monomers using new initiating systems, metathesis polymerizations with new catalysts. Pseudo‐living radical polymerizations, leading to new block copolymers and new mechanisms of radical ring opening, leading to new polymers and copolymers are included. From the field of stepwise polymerization, new developments in phase‐transfer catalysis and activated polycondensation mechanisms are described. New polymer architecture, important for modern applications in new materials is represented by the section on liquid‐crystalline polymers.
13C NMR microstructure determinations of low‐density polyethylene homopolymers and copolymers
Authors: Randall J. C. , Ruff C. J. , Kelchtermans M.
Published: September 2010

Low‐density polyethylenes, prepared by free radical processes in high‐pressure reactors, are dendritic polymers with complex microstructures. Both long‐ and short‐chain aliphatic branches are produced by Roedel intramolecular and intermolecular chain‐transfer reactions during free‐radical processes. Unlike catalytically produced linear low‐density polyethylenes, high‐pressure free‐radical polymerization processes possess the capability for incorporating polar comonomers, which leads to copolymers, such as poly(ethylene‐co‐vinylacetate), poly(ethylene‐co‐acrylic acid), poly‐(ethylene‐co‐methylacrylate), etc. Although it is not often discussed, these comonomer units can also be involved in Roedel intramolecular and intermolecular chain‐transfer reactions either as terminal units or as sites for chain‐transfer during a ‘backbiting’ step. These additional reactions lead to even more complex structures. In this study, the various ways comonomer units can be incorporated into low‐density polyethylene chains, as a consequence of Roedel chain‐transfer chemistry, are identified and the microstructures are given in terms of aliphatic branching as well as type and amount of comonomer structures. This leads to more complete structural determinations that yield results consistent with the melting behavior and that are useful in establishing structure‐property relationships.
Review of 1H‐ and 13C‐NMR spectroscopy of (meth)acrylate (co)polymers
Authors: Gaur H. Angad
Published: September 2010

A review of 1H‐ and 13C‐NMR investigation of (meth)acrylate homo‐ and copolymers and of (meth)acrylate‐styrene copolymers is presented. The results obtained by these techniques are discussed in terms of compositional and stereo‐conformational sequence distributions. Topics also covered are 2D NMR and computational techniques.
(1R)‐ and (1S)‐5‐demethyl‐8,16‐methanobacteriorhodopsin and its properties. The synthesis and spectroscopy of 5‐demethyl‐8,16‐methanoretinal in optically active and isotopic forms
Authors: Spijker‐Assink M. B. , Robijn G. W. , Ippel J. H. , Lugtenburg J. , Groen B. H. , van Dam K.
Published: September 2010

(All‐E)‐5‐demethyl‐8,16‐methanoretinal was prepared in both optical antipodes (1R and 1S), as well as in their 9‐Z and 13‐Z forms. The interaction of the 1R and 1S forms with bacterioopsin shows that there is a clear chiral recognition on the formation of the bacteriorhodopsin analogues, reflected in the rate of binding and ϵmax values. The two bacteriorhodopsins with optically active chromophores have an identical λmax value and show the same efficiency of the light‐driven proton pump. The absence of the 5‐methyl group leads to a 50% lower proton‐pump efficiency than the native system. In addition, for the racemic 5‐demethyl‐8,16‐methanoretinal, the 5‐2H, 7‐2H, 5,7‐2H2 and 5,7,16a,16a‐2H4 isotopomers in the various isomeric forms all‐E, 9‐Z and 13‐Z were also prepared.
Near absolute regio‐, diastereo‐, and enantioselectivity in a palladium: Catalyzed alkylation using an uncommon chiral auxiliary
Authors: Sjouken Ronald , Ebens Rijko , Kellogg Richard M.
Published: September 2010

Condensation of R‐(+)‐1‐(2‐chlorophenyl)‐2,2‐dimethyl‐propan‐1,3‐diol (2) with a derivative (1) of 1‐formylcyclohexene substituted in the 3‐position with an acetoxy group proceeded with absolute stereospecificity at the acetal center. Catalytic alkylation of the π‐allyl complex obtained upon reaction with Pd with the anion of dimethylmalonate proceeded at the 3‐position of the cyclohexyl ring with complete stereocontrol.
Synthesis of β‐amino α‐hydroxy carboxylic esters from oxiranecarboxylic esters
Authors: Legters Johan , van Dienst Erik , Thijs Lambertus , Zwanenburg Binne
Published: September 2010

3‐Aryl‐3‐azido‐2‐hydroxypropanoic esters, prepared from the corresponding 3‐aryl‐oxirane‐2‐carboxylic esters by ring opening with sodium azide, were reduced with tin(II) chloride dihydrate in methanol to give 3‐amino‐3‐aryl‐2‐hydroxypropanoic esters in good yields. Under these conditions, halogen substituents in the aromatic rings were not affected. The nitro group, however, was partially reduced to the amino group. Treatment of aliphatic oxirane‐2‐carboxylic esters with acetonitrile in the presence of boron trifluoride etherate led to regiospecific formation of 2,4‐dialkyl‐2‐oxazoline‐5‐carboxylic esters, resulting from reaction of the nitrile at C3. Acidic hydrolysis of these oxazoline‐5‐carboxylic esters gave the corresponding 3‐(acylamino)‐2‐hydroxy carboxylic esters. With these two complementary methods, both aryl‐ and alkyl‐substituted β‐amino α‐hydroxy acid derivatives are accessible.
Solid‐phase synthesis of oligodeoxynucleotides containing 4‐alkoxythymidine residues
Authors: Roelen H. C. P. F. , Brugghe H. F. , van den Elst H. , van der Marel G. A. , van Boom J. H.
Published: September 2010

Immobilized and fully protected oligodeoxynucleotides containing a 4‐(1,2,4‐triazolyl)‐thymidine residue at a predetermined position were prepared according to a well‐established phosphite triester methodology using 2‐cyanoethyl phosphoramidites of a 4‐(1,2,4‐triazolyl)‐substituted thymidine and standard protected nucleosides. Treatment of the immobilized oligomer with methanol, ethanol or n‐propanol in the presence of DBU at 50°C gave the corresponding oligonucleotides containing 4‐methoxy, 4‐ethoxy‐ or 4‐n‐propoxythymidine residue.
Some new cationic di‐ and tricarbonyl complexes of technetium(I)
Authors: Castro H. H. Knight , Hissink C. E. , Teuben J. H. , Vaalburg W. , Panek K.
Published: September 2010

Some new low‐valent, cationic complexes of technetium‐99 have been prepared. Oxidation of Tc2(CO)10 (1) with NOPF6 in acetonitrile gave [Tc(CH3CN)(CO)5]PF6 (2) quantitatively. This complex constitutes a useful precursor for cationic carbonyl complexes, as exemplified by a variety of reactions with bi‐ and tridentate ligands from which air‐stable, water‐soluble complexes of type [LTc(CO)3]+ (L = 1,4,7‐triazacyclononane, 1,4,7‐trimethyl‐1,4,7‐triazacyclononane and 1,4,7‐trithiacyclononane) have been isolated and characterized. A series of mixed complexes of technetium(I) of general formula {Tc(N,N)[P(OR)3]2(CO)2}PF6 (N,N = 2,2′‐bipyridine, 4,4′‐dimethyl‐2,2′‐bipyridine and R = methyl, isopropyl) has also been prepared.
Reductive cleavage of the carbonphosphorus bond with alkali metals. III. Reactions of arylalkylphosphines
Authors: van Doorn Johannes A. , Meijboom Nico
Published: September 2010

The reductive cleavage of phenylalkylphosphines Ph2PR, PhPR2 (R = Bu, iPr) with Na/NH3 is unselective: both phenyl and alkyl groups can be cleaved and Birch reduction may occur. Reaction of Ph2tBuP gives a high yield of diphenylphosphide. Polar groups (CO2Na, SO3,Na) at the ω position of primary alkyl groups may lead to an increase in selectivity; Birch reduction is suppressed and a functionalised secondary phosphide is obtained.

From diarylbenzyl‐ and diarylallylphosphines, the benzyl and allyl groups are selectively removed; Ar2PH and ArRPH are formed in high yield after hydrolytic work‐up unless the aryl group bears F, CF3, or (CH3)2N substituents. From the reaction mixture of Ph2PCH2Ph we have isolated 1,2‐ ‐diphenylethane.

2‐Methoxyphenyl and 2,6‐dimethoxyphenyl groups are selectively removed from Ar2BuP, ArPhBuP and Ar2P(CH2)3PAr2, forming ArBuPH, PhBuPH and ArP(H)(CH2)3(H)PAr, respectively. A double‐cleavage reaction of Ar2RP may occur in low yield. 2,6‐(Dimethoxyphenyl‐dibutylphosphine gives dibutylphosphine in moderate yield. When compounds with a 2,6‐dimethoxyphenyl moiety are allowed to react with Li/THF, removal of a methyl group leads to novel phosphinophenols. It is concluded that cleavage of alkyl groups R selectively occurs when R° is relatively stable (tBu, PhCH2 > iPr > Bu).
Sulfonation of anisole, phenol, toluene and related alkyl and alkoxy derivatives with SO3. The influence of the solvent system on the reactivity and the sulfonic acid product distribution
Authors: Ansink Harold R. W. , Cerfontain Hans
Published: September 2010

The reactions of anisole (1), phenol (2), the alkoxy‐ and alkylphenyl ethers 3–11, toluene (12) and the o‐dialkylbenzenes 13–15 with sulfur trioxide in dichloromethane or trichlorofluoromethane have been studied. Our results have been compared with those obtained with the same substrates upon reaction with SO3 in nitromethane and dioxane. We show that ortho substitution is enhanced for sterically unhindered phenyl ethers and phenols due to complex formation between SO3 and the C(sp2)‐bonded oxygen when dichloromethane is used as solvent instead of nitromethane or dioxane. This is mainly as a result of intramolecular SO3, transfer from the oxygen to the ortho carbon and subsequent conversion of the resulting σ‐complex into the ortho sulfonic acid.
Synthesis of phosphatidylinositol analogs containing sulfonylmethylene or methyleneoxy linkages
Authors: Elie C. J. J. , Brounts D. M. , Dreef C. E. , van der Marel G. A. , van Boom J. H.
Published: September 2010

Alkylation of the α‐lithio anion of 2,3,4,5,6‐penta‐O‐benzyl‐myo‐inositol 1‐(methanesulfonate) with 1,2‐O‐isopropylidene‐sn‐glycerol 3‐(trifluoromethanesulfonate) gave, after removal of the acetonide function followed by palmitoylation and finally hydrogenolysis of the benzyl protecting groups, the racemic phosphatidylinositol analog 3. The methyleneoxy‐containing inositol phospholipid 4 was prepared by iodonium‐ion‐assisted condensation of 1,2‐O‐isopropylidene‐3‐(methylthiomethyl)‐sn‐glycerol with 2,3,4,5,6‐penta‐O‐benzyl‐myo‐inositol, and subsequent removal of all protecting groups.
Computer‐executed synthesis planning, a progress report
Authors: Dogane I. , Takabatake T. , Bersohn M.
Published: September 2010

We describe the Sumitomo Chemical Company computer program, which designs synthetic routes for organic molecules, without consulting a user. There are only approximately 2500 reactions stored in the program. Significant advances in the automation of reaction input are presented. We also give some examples of synthetic routes proposed by the program, one being an enantiospecific and stereospecific route for the synthesis of the antibiotic chloramphenicol.
Erythronolide B: Analysis of the synthesis pathway proposed by the Lilith program
Authors: Baumer Luca , Compagnari Ilaria , Sala Giordano , Sello Guido
Published: September 2010

Computer‐Assisted Organic Synthesis (CAOS) has become a common tool in synthesis pathway design. Many different approaches exist, each giving suggestions for the exploration of the synthetic space. Validation of the proposed solutions can be done both by using different programs and by experimental realization of the synthesis. To this end, a molecule of medium complexity, erythronolide B, has been used to make a three‐way comparison using results obtained by the program LHASA, in the laboratory, and by the program Lilith. The importance of using different sources in studying a synthesis pathway is discussed, with respect to achieving the best result from each approach. The high level of convergence in the syntheses proposed by the Lilith program is the most interesting characteristic of the program's results. Moreover, reproduction of the syntheses proposed by the other approaches guarantees the applicability of the Lilith program to real synthetic problems. A brief outline of the Lilith program is included.
Some recent progress in the development of the LHASA computer system for organic synthesis design: Starting‐material‐oriented retrosynthetic analysis
Authors: Johnson A. Peter , Marshall Chris , Judson Philip N.
Published: September 2010

One of the strategies used by chemists when designing retrosynthetic routes is to direct them towards particular starting materials which have been chosen because they have structural similarities to the target compounds. This paper illustrates uses of the starting‐material strategy in the LHASA program. To apply the strategy, LHASA must be able to select potential starting materials, perceive how they map onto the target compound, recognise the structural changes implied by the mapping if the target structure is to be converted retrosynthetically into that of the starting material, find chemical reactions that can bring about the changes and decide upon the order in which they should be done.
Descriptions of reactions: Their logic and applications
Authors: Hendrickson James B.
Published: September 2010

Three systems of reaction description, from Ugi, Fujita, and Hendrickson, are examined and compared. They are shown to be essentially identical, and are rationalized here into a single simplified representation. The application of these systems to reaction retrieval, synthesis, and the invention of new reactions is also described.
Lewis‐acid‐induced reactions of α‐methoxyglycinamide derivatives with silyl enol ethers. Formation of 3‐amino‐2‐pyrrolidinones and 3‐amino‐2‐pyrrolinones
Authors: Roos Eric C. , Hiemstra Henk , Speckamp W. Nico , Kaptein Bernard , Kamphuis Johan , Schoemaker Hans E.
Published: September 2010

In order to develop an expedient synthetic route to γ‐oxo‐α‐aminocarboxamides, five different α‐(alkoxycarbonyl)amino‐α‐methoxyacetamides were subjected to borontrifluoride‐etherate‐mediated reactions with one silyl ketene acetal and four silyl enol ethers. Reactions of primary and secondary amides did not lead to the desired CCbond formation. Reactions of the tertiary N,N‐dimethylamide gave the expected γ‐oxo‐α‐aminocarboxamides. The reaction of an N‐methoxy‐N‐trimethylsilylcarboxamide with the ketene acetal also proceeded normally. However, the initial products of the latter amide with silyl enol ethers reacted further by cyclization, respectively, to give a cyclic N‐ methoxy‐N‐acyliminium intermediate. Depending on structural features of the enol ether used, this iminium intermediate suffered either proton loss and isomerization to give protected 3‐amino‐1‐methoxy‐δ3‐pyrrolin‐2‐ones, or underwent a second coupling with the enol ether to give protected 3‐amino‐1‐methoxypyrrolidin‐2‐ones.
Synthesis of a highly unsaturated fatty acid moiety of lipo oligosaccharides determining host‐specificity in rhizobium
Authors: Verduyn R. , Lagas R. M. , Dreef C. E. , van der Marel G. A. , van Boom J. H.
Published: September 2010

The phosphonate ethyl 6‐(diethylphosphono)‐2E,4E‐hexadienoic acid is a suitable synthon for the highly stereoselective preparation of 2E,4E,6E,11Z‐octadecatetraenoic acid and its 2E,4E,6E‐ analog.
Synthesis, characterization and metal‐uptake behaviour of pyrazole ligands immobilized on silica
Authors: Verweij P. D. , Haanepen M. J. , de Ridder J. J. , Driessen W. L. , Reedijk J.
Published: September 2010

The novel didentate ligand 2‐(3,5‐dimethyl‐1‐pyrazolyl)ethylamine (Naed) and the tridentate ligand bis[2‐(3,5‐dimethyl‐1‐pyrazolyl)ethyl] amine (ddaH) were immobilized onto silica by two different methods. The first method involves the coupling of the ligand to silica, previously modified with (3‐glycidyloxypropyl)trimethoxysilane (GLYMO). The second method involves the coupling of the ligand to the oxirane ring of GLYMO in a homogeneous reaction, followed by grafting onto silica, yielding the highest ligand concentrations on the silica (about 0.3 mmol/g silica). With the first method, only part of the epoxy group reacts with the ligand. With Naed, tertiary amines are also formed through reaction of the primary amine group of the ligand with two epoxy groups.

These new ion‐exchange materials selectively adsorb Cu2+ (maximum capacity 0.11–0.26 mmol Cu2+ per gram of ion exchange) at pH > 2 from aqueous solutions containing a mixture of the bivalent metal ions, Cu2+, Cd2+, Zn2+, Ni2+ and Co2+. For products containing the didentate ligand Naed as the chelating group, the metal‐ion capacity decreases rapidly with decreasing pH, while the Cu2+ ‐uptake capacity for the product containing the tridentate ligand ddaH is comparatively high at low pH.
Acid induced decomposition of coenzyme B12 and variants
Authors: Gerards L. E. H. , Balt S.
Published: September 2010

The acid catalyzed heterolytic cleavage of the CoC bond in coenzyme B12 (1) was studied using the ‘excess acidity’ functions of Cox and Yates. The results are compared to the acid induced decomposition of (methyl‐5‐deoxy‐ribofuranosyl)‐(2) and (2‐ethoxyethyl)cobalamin (3). Evidence is presented to view the CoC bond cleavage in the compounds (1) and (2) as an A2 mechanism with water as the nucleophile or as an Ia substitution at Co3+, and in (3) as an A1 mechanism. Volumes of activation are consistent with the proposed mechanism.
1H NMR conformational analysis of (3‐aminopropyl)triethoxysilane
Authors: de Brabander‐van den Berg Ellen M. M. , Ippel Johannes H. , Lugtenburg Johan , Jenneskens Leonardus W.
Published: September 2010

The 1H NMR spectrum of (3‐aminopropyl)triethoxysilane (1) was analyzed to gain insight into the population distributions of the anti and gauche conformers: xa and xg, respectively, across the carboncarbon bonds (C(1)‐C(2) (bond I) and C(2)‐C(3) (bond II) of the 3‐aminopropyl group. Values of xa of 0.76/0.71 [bond I, 3J(AB)/3J(A′B)] and 0.57/0.53 [bond II, 3J(BC)/3J(B′C)], respectively, were calculated. The absence of solvent dependence of the anti‐gauche equilibria indicates that specific solute‐solvent complexation does not contribute to the intramolecular interactions.
Synthesis of L‐glucose derivatives from D‐glucose and L‐arabinose
Authors: Smid P. , Noort D. , Broxterman H. J. G. , van Straten N. C. R. , van der Marel G. A. , van Boom J. H.
Published: September 2010

L‐Glucose derivatives are prepared by two different routes. The first involves a modification of the previously reported multi‐step approach by Shiozaki8, starting from a D‐glucurono‐1,5‐lactone derivative, resulting in the isolation of 2,3,4,6‐tetra‐O‐benzyl‐L‐glucopyranose. The other route comprises the synthesis of penta‐O‐acetyl‐L‐glucopyranose via a highly stereoselective addition of [(phenyldimethylsilyl)methyl]magnesium chloride with 2,3,5‐tri‐O‐benzyl‐L‐arabinofuranose.
Synthesis and receptor‐affinity profile ofN‐hydroxytryptamine derivatives for serotonin and tryptamine receptors. A molecular‐modeling study
Authors: Dijkstra Gerard D. H. , Tulp Martin Th. M. , Hermkens Pedro H. H. , van Maarseveen Jan H. , Scheeren Hans W. , Kruse Chris G.
Published: September 2010

The synthesis and the affinities for serotonin and tryptamine receptors of a series ofN‐oxy derivatives of tryptamine (6–8, 13–14) are reported. It was found thatN‐hydroxytryptamine (6) is a relatively selective ligand for the 5‐HT1Creceptor. The receptor‐binding data are interpreted by a molecular modeling study in which the binding sites of the 5‐HT1Aand 5‐HT1Creceptors are compared. An asparagine residue present in helix 7 of 5‐HT1Abut absent in 5‐HT1Cplays a crucial role. On the basis of a three‐dimensional model of the seven transmembrane regions of the 5‐HT1Areceptor a hydrogen‐bond interaction is predicted between this asparagine residue and one of the oxygens of an aspartic acid residue on helix 3, leaving only one oxygen atom for ligand interaction. In the 5‐HT1Cboth oxygens of the aspartic acid residue on helix 3 are free to interact via a doubly hydrogen‐bonded complex with theN‐hydroxy moiety of6.N‐Methoxy derivative13lacks this additional hydrogen‐bond possibility and is devoid of binding affinity, presumably as a result of electrostatic repulsion.
Synthesis and pharmacological evaluation of 5,6,7,8‐tetrahydro‐6‐[propyl[2‐(2‐thienyl)ethyl]amino]‐1,2‐naphthalenediol: A novel non‐selective dopamine‐receptor agonist
Authors: Copinga Swier , Dijkstra Durk , de Vries Jan B. , Grol Cor J. , Horn Alan S.
Published: September 2010

Based on the hypothesis that simultaneous stimulation of dopamine D1and ‐D2receptors could be beneficial for the treatment of Parkinson's disease7,13, we prepared 5,6,7,8‐tetrahydro‐6‐[propyl[2‐(2‐thienyl)ethyl]amino]‐1,2‐naphthalenediol (PTAT.4), the diol analogue of N‐0437 (3), as a potential mixed D1/D2‐receptor agonist. The synthesis of4was carried out via a new strategy. The crucial step in this strategy was the conversion of 1‐diazo‐4‐(2,3‐dimethoxyphenyl)‐2‐butanone (15) to the key intermediate 5,6‐dimethoxy‐2‐tetralone (9) via a rhodium(II)‐ acetate‐catalysed cyclisation, followed by transformation under the influence of trifluoroacetic acid. Pharmacological evaluation of the dopaminergic properties of PTAT (4) revealed that this compound displays high affinity for both D1and D2receptors and has the same ability as DPAT (1), a mixed D1/D2‐receptor agonist, to induce locomotor activity in mice rendered acutely akinetic with reserpine.
Monoamine re‐uptake inhibiting 1‐[2‐[(phenoxyphenyl)methoxy]ethyl]‐ piperazines as potential antidepressants
Authors: Wieringa J. , van den Meerendonk A. , Steenvoorden J. , Heeres G. , van Bakel F. , Roeters T. , van der Hulst R. , Den Blanken A. , Leysen D. , Plate R. , de Boer Th. , Rijk H.
Published: September 2010

A series of 1‐[2‐[(2‐phenoxyphenyl)methoxy]ethyl]‐4‐(3‐phenylpropyl)piperazines 17–50 (Figure 1) were prepared and tested as inhibitors of biogenic amine re‐uptake. In our search for antidepressants, the relationship between their in vitro and in vivo activity as dopamine‐reuptake inhibitors is described quantitatively by using Retention Index values determined by reversed‐phase liquid chromatography.
Homology model‐building studies of human thrombin: Optimisation of modelling protocol and comparison with X‐ray structure
Authors: Koymans Luc M. H. , Grootenhuis Peter D. J. , Haasnoot Cornelis A. G.
Published: September 2010

The present paper evaluates the effect of several parameters on the accuracy of homology model‐built structures of human thrombin. In order to appraise the merits of such a homology model‐building study as a practical basis for direct drug‐design purposes, this study was limited to the widely used “standard” alignment and loop‐modelling methods implemented in the Quanta/CHARMm 3.0 software. The parameters studied were the alignment method, the choice of the template protein, and the molecular dynamics refinement protocol. The resulting models were energy‐minimised and compared with the energy‐minimised crystal structure of thrombin. It was found that the method of alignment is the dominating parameter: the alignment algorithm giving the most accurate models is one that is based upon the three‐dimensional overlap of structurally conserved regions in related proteins. The choice of the template protein structures, which all showed a ± 30% sequence identity with thrombin, turned out to be less important for the accuracy of the final model. In our hands, molecular dynamics simulations at 300 and 1000K failed to improve the predictive value of the models. The overall root‐mean‐square deviation between the best model and the minimised crystal structure of thrombin amounted to 2.9 Å. Detailed comparison of the models with the experimentally determined 3D structure of thrombin leads to the conclusion that although a homology‐building study may result in a three‐dimensional model that yields a good general idea of the protein structure, rather large structural uncertainties in the proximity of insertions of more than 4 amino acids limit its practical use for direct drug‐design efforts.
Towards a rational design for resolving agents. Part V: Substituent effects in the resolution of ephedrine using a series of cyclic phosphoric acids
Authors: van der Haest Albertus D. , Wynberg Hans , Leusen Frank J. J. , Bruggink Alle
Published: September 2010

The effects of various aromatic substituents in both ephedrine and a cyclic phosphoric acid on the quality of resolution via diastereomeric salt formation are investigated. The diastereo‐selective synthesis of a novel series of chloro‐substituted ephedrines is described. These chloroephedrines can be resolved efficiently with some of the cyclic phosphoric acids. By studying the physical properties of nineteen pairs of diastereomeric salts, we show that the quality of the resolution depends mainly on the aromatic substituent of the cyclic phosphoric acid, whereas substituents at the phenyl ring of ephedrine play a secondary role.
Novel rearrangement during dehydration. Construction of the guaianolide skeleton
Authors: Banerjee Ajoy K. , Vera William
Published: September 2010

On treatment with phosphorus oxychloride, the decalin derivative 6 underwent rearrangement yielding principally the perhydroazulene derivative 8. Similar rearrangement was also observed on dehydration of the decalin derivative 9.
Gas‐phase oxychlorination of benzene
Authors: Born Jan G. P. , van der Wart Hans W. A. , Mulder Peter , Louw Robert
Published: September 2010

Homogeneous gas‐phase oxychlorination of benzene has been examined in a flow system between 722 and 1174K. Experiments were performed at atmospheric pressure with nitrogen as an inert carrier gas, containing about equal molar amounts of oxygen, HCl and benzene. Apart from chlorobenzene, substantial amounts of o‐ and p‐chlorophenol are produced. Using benzonitrile rather than benzene, the three isomers of ClC6H4CN are formed in about equal amounts. These findings suggest a homolytic mechanism with aryl radicals as key intermediates. Thermokinetic analysis points to formation of chlorophenols via reaction of phenoxyl (formed from phenyl and oxygen) with HOCl. Chlorination, C6 H6 → C6H5Cl, is explained by reaction between phenyl radicals and HOCl. With increasing temperature (and, therefore, oxygen consumption), slow combustion is replaced by pyrolysis as the major reaction channel. As a result, above ca. 1000K, the production of chlorobenzene diminishes, [C6H5Cl] ultimately being governed by the equilibrium: C6H6 + HCl ⇌ C6H5Cl + H2.
Reactivity of zinc dialkyldithiocarbamates towards halogen‐substituted olefins
Authors: Versloot P. , Dargan P. , Haasnoot J. G. , Reedijk J. , van Duin M. , Put J. , Goubitz K.
Published: September 2010

The reaction of bis(dimethyldithiocarbamato)zinc(II) [Zn(dmtc)2] with halogen‐substituted 2,3‐dimethyl‐2‐butene (e.g., 1‐bromo‐2,3‐dimethyl‐2‐butene; tme‐Br) causes substitution of bromide by the dmtc ligands. Depending on the polarity of the solvent, this results either in a complex ZnBr2 (tme‐dmtc)2, in which the coupling product remains coordinated to the metal, or in the liberation of the ligand, producing ZnBr2 and tme‐dmtc. Crystals of tme‐dmtc have been obtained from methanol solution. An X‐ray structure of this solid has been determined; relevant data: C9H17NS2, Mr = 204.4, monoclinic, P21, a = 8.2087(5), b = 7.3551(5), c = 10.2791(8) Å, β = 106.437(6)°, V = 595.25(8) Å3, Z = 2, Dx = 1.14 g·cm−3, λ(CuKα) = 1.5418 Å, μ(CuKα) = 36.25 cm−1, F(000) = 222, room temperature. Final R = 0.069 for 853 observed reflections.
The influence of the 5‐methyl group in bacteriorhodopsin
Authors: Groesbeek M. , de Vries E. F. J. , Berden J. A. , Lugtenburg J.
Published: September 2010

All‐E‐5‐bromo‐5‐demethylretinal was prepared in 6% yield starting from 4,4‐dimethyl‐2‐cyclohexenone via 2‐bromo‐6,6‐dimethyl‐1‐cyclohexenecarboxaldehyde. The crucial step in the preparation of the intermediate is a 2,3 Wittig rearrangement. 5‐Bromo‐5‐demethylbacteriorhodopsin is easily formed from all‐E‐5‐bromo‐5‐demethylretinal and bO. Due to the fact that the bromo substituent has about the same steric requirements as the 5‐methyl group, the influence of electronic factors on the properties of bacteriorhodopsin could be studied. We conclude that the contribution of the 5‐methyl group in bR to the proton‐pump action and opsin shift is due to its electron‐donating properties.
Coordination properties of the didentate N,O ligand 1‐(2‐hydroxyethyl)‐3,5‐dimethylpyrazole (hl). Crystal structure of [Cu(HL)2(NO3)2] and [Cu(L)Br]2
Authors: Driessen W. L. , Gorter S. , Haanstra W. G. , Laarhoven L. J. J. , Reedijk J. , Goubitz K. , Seljée F. R.
Published: September 2010

The didentate N,O donor ligand 1‐(2‐hydroxyethyl)‐3,5‐dimethylpyrazole (N‐hed) renders two kinds of coordination compounds, viz. [M(N‐hed)2(NO3)2] with M=Co, Ni, Cu, and Zn, [Ni(N‐hed)2(NCS)2], and [Cu(N‐hed)2Cl2] in which the ligand is neutral, and [Cu(N‐oed)X]2 with X=Cl, Br, and NO3 in which the ligand N‐hed is in its deprotonated form, viz. 1‐(2‐oxidoethyl)‐3,5‐dimethylpyrazole (N‐oed).

The crystal structure of [Cu(N‐hed)2(NO3)2] shows it to be mononuclear, with the copper ion at a centre of symmetry. Monoclinic, space group P21/c, a = 7.8176(8), b = 14.93(2), c = 8.4076(8) Å, β = 92.62(2)°, Z = 2; R = 0.036 (Rw = 0.038) for 2132 significant reflections. The copper(II) ion is in a tetragonal‐distorted, elongated‐octahedral environment of two trans pyrazole nitrogen atoms at 1.974(2) Å, two trans hydroxyl oxygen atoms at 1.991(2) Å, and two trans oxygen atoms of monodentate coordinated nitrate anions at 2.561(2) Å. The structure is stabilized by strong intramolecular hydrogen bonds between the hydroxyl group of the coordinated ligand and an oxygen atom of the coordinated nitrate ion with a short O‐O distance of 2.599(2) Å. The metal ions in the compounds [M(N‐hed)2X2] are octahedrally surrounded by two nitrogen and two oxygen atoms of the ligand and by two anion donor atoms (respectively O, N, or Cl).

The crystal structure of [Cu(N‐oed)Br]2 shows it to be dinuclear. Triclinic, space group P2/1, a = 4.5213(6), b = 8.484(1), c = 13.052(7) Å, α = 81.50(3), β = 85.79(4), γ = 77.79(2)°, Z = 1, R = 0.148 (Rw = 0.224) for 1534 reflections. The copper ions are bridged by two oxo atoms of the deprotonated ligands with a Cu‐Cu distance of 3.042(4) Å. Each Cu(II) ion is in a distorted square‐planar O2NBr environment. The compounds [Cu(N‐oed)X]2 are diamagnetic and EPR‐silent.
Binding of water and solvent molecules in a 25‐membered‐ring host compound
Authors: Vögtle Fritz , Brodesser Gisela , Nieger Martin , Rissanen Kari
Published: September 2010

The macrocyclic 15‐ and 25‐membered‐ring pyridine oligomers1and2containing three and five methoxy substituents in the 4‐position of the pyridine rings were prepared byMüller‐Röscheisencyclization and then isolated by chromatography. They are attractive as synthetic endobasic receptor molecules. X‐ray structure analysis exhibits the inclusion of hydrogen‐bonded solvent molecules (water and trichloromethane) inside the pentameric macrocycle2.
Catalytic cyclophanes VII. Esterase activity of a bisimidazolyl‐cyclophane
Authors: Chao Ito , Diederich François
Published: September 2010

We report the synthesis of the novel tetraoxa[6.1.6.1]paracyclophane 3 with two imidazole residues attached to the benzene rings of one of the two diphenylmethane spacers that shape the macrocyclic cavity. Four acetic acid residues diverge from the central carbon atoms of the two spacer units and ensure solubility of 3 in water and binary aqueous solvent mixtures. Cyclophane 3 forms stoichiometric inclusion complexes with nitronaphthyl acetates in aqueous phosphate buffers (pH 8) and catalyzes the hydrolysis of bound substrates under turnover conditions.
Synthesis, conformations and redox properties of diametrical calix[4]arenediquinones
Authors: Casnati Alessandro , Comelli Emma , Fabbi Massimo , Bocchi Vittorio , Pochini Andrea , Ungaro Rocco , Mori Giovanni , Ugozzoli Franco , Lanfredi Anna Maria Manotti
Published: September 2010

Several calix[4]arenediquinones3a‐ehaving quinone moieties in opposite positions (diametrical) have been synthesized by oxidation of 25,27‐dialkoxycalix[4]arenes2a‐ewith Tl(NO3)3· 3H2O in organic solvents. The conformational properties of these compounds have been established in the solid state by X‐ray crystallography and in solution by variable‐temperature dynamic NMR. We found that the calix[4]arenediquinones3a‐eare more flexible than the parent 25,27‐dialkoxycalix[4]arenes2a‐ein solution and tend to assume two different partial cone structures in the solid state, depending on the steric bulkiness of the alkoxy groups. Cyclic voltammetry reveals that the redox properties of calix[4]arenediquinones3a‐edepend on their conformational properties.
Synthesis and X‐ray structure of a novel cavity‐containing dinuclear nickel(II) complex
Authors: Gosling P. A. , Sijbesma R. P. , Nolte R. J. M. , Spek A. L.
Published: September 2010

Compounds consisting of a substrate‐binding site and a NiII or MnIII salen moiety have been synthesized. These compounds are able to epoxidise a variety of alkenes in the presence of sodium hypochlorite or iodosylbenzene. The X‐ray structure of the nickel(II) complex is reported.