Enzymatic synthesis of ω-carboxy-β-hydroxy-(l)-α-amino acids

Commercially available ω-carboxy-aldehydes and glycine have been subjected to the catalytic action of an l-threonine aldolase from Escherichia coli to give the corresponding β-hydroxy-α-(l)-amino acids as a mixture of erythro/threo epimers.Specifically, the reaction with glyoxylic acid (2) gave the epimeric β-hydroxy-(l)-aspartates (t,e)-9 that could be isolated by ion-exchange chromatography in 67% yield. Following esterification and N-Boc protection, the two epimers could be isolated as pure compounds.Similarly, the aldolase-catalyzed addition of glycine to succinic semialdehyde (4) gave the expected mixture of β-hydroxy-l-α-aminoadipic acids (t)-12 and (e)-12 in 34% yield.     

Chlorination of trans-1,2-Diarylethenes in Chloroform and Acetic Acid

When chlorinated in chloroform, (E)-stilbenes bearing electron-donor substituents in the para position of the benzene ring give threo-1,2-diaryl-1,2-dichloroethanes, while meta-substituted (E)-stilbenes, predominantly erythro isomers, irrespective of the nature of the substituent. The reactions in acetic acid result in preferential formation of threo-1,2-dichloro- and threo-1-acetoxy-1,2-diaryl-2-chloroethanes.     

Über die Stereospezifität der α-Alkylierung von β-Hydroxycarbonsäureestern. Vorläufige Mitteilung

About the Stereospecific α-Alkylation of β-Hydroxyesters It was found, that dianions derived from β-hydroxyesters with lithium diisopropylamide (LDA) at ?50 to ?20° were alkylated stereospecifically (Scheme 1). The stereospecificity was 95–98%, the threo-compound (threo -2, -3 and -4) being the main product. This was proved for threo -2 and -3 by preparing the β-lactones 7 and 8 , respectively, which were pyrolyzed to trans-1, 4-hexadiene (9) and trans-1-phenyl-2-butene (10) , respectively (Scheme 2). Moreover, the acid threo -6 from threo -3 was converted by dimethylformamide-dimethylacetal to cis-1-phenyl-2-butene (11) (s. footnote 6). The alkylation of α-monosubstituted β-hydroxyesters also turned out to be stereospecific. Reduction of 16 and 18 with actively fermenting yeast furnished (+) -17 and (+) -2. respectively (Scheme 4), which were each mixtures of the (2R, 3S)- and the (2S, 3S)-isomers. Alkylation of (+) -17 with allyl bromide yielded after chromatography (2S, 3S) -19 and of (+) -2 with methyl iodide (2R, 3S) -19 , the oxidation of which finally gave (S)-(?) -20 and (R)-(+) -20 , respectively.     

Characterization and sources of extractable organochlorine in white sucker downstream from bleached kraft pulp mills

Organochlorine, obtained by extraction with hexane–acetone mixture (3?:?1) of fillets of white sucker (Catostomus commersoni) sampled downstream of pulp mills and in a reference river, was characterized by gel-permeation chromatography, transesterification, neutron activation analysis, and gas chromatography with halogen-sensitive detection. It was found that over 78% of the extractable organochlorine (EOCl) is of relatively high molecular weight (>～350). Chlorinated fatty acids account for 43–80% of EOCl in the high-molecular-weight portion, while chlorobenzenes, chlorinated pesticides, and polychlorinated biphenyls account for 4–55% of EOCl in the low-molecular-weight portion. Though undetectable in reference fish, three particular chlorinated fatty acids, i.e. threo-5,6-dichlorotetradecanoic, threo-7,8-dichlorohexadecanoic and threo-9,10-dichlorooctadecanoic acids, are characteristic of EOCl from fish collected downstream of bleached kraft pulp mills using chlorine-based bleaching, representing about 30% of total EOCl, of which threo-5,6-dichlorotetradecanoic acid alone accounts for 60–70%. It is thus evident that, among chlorinated compounds discharged from bleached kraft pulp mills, threo-9,10-dichlorooctadecanoic acid, presumably generated in chlorine-based bleaching processes, is the most bio-accumulative in fish and can be biodegraded by fish into dichlorohexadecanoic and dichlorotetradecanoic acids, presumably via β-oxidative metabolism. These three compounds were also identified in suspended solids isolated from biologically treated final effluent discharged from a bleached pulp mill using 50% ClO₂ substitution, thus confirming the effluent-related source for downstream fish. The finding also suggests that β-oxidation of dichlorooctadecanoic acid may also be operative in micro-organisms.     

Conformational study of methyl esters of some aliphatic erythro- and threo-dichlorocarboxylic acids

The average conformations of methyl esters of some aliphatic erythro- and threo-dichlorocarboxylic acids in dilute carbon tetrachloride solutions have been determined from the vicinal proton–proton coupling constants and ¹H NMR shifts. The ¹³C shift differences between the erythro and threo forms are compared and discussed with regard to the differences in the average conformations.     

Applications of 1,4-addition of grignard reagents to α,β-unsaturated acid derivatives. III—configuration studies of α,β-diaryl-α,β-dialkylpropionitriles

The configuration of twenty-four different α,β-diaryl-α,β-dialkylpropionitriles has been determined using nuclear magnetic resonance spectra. The erythro form showed greater deshielding of the methine hydrogen and alkyl groups in its spectra than the corresponding threo isomer. The former, however, showed less deshielding of the aryl groups than the threo isomer. Infrared spectra were not suitable for assignments of configuration.     

Beiträge zur Chemie des Phosphors. 134. Über die Triphosphane H(t-BuP)3H,Li(t-BuP)3Li und Me3Si(t-BuP)3SiMe3

Contributions to the Chemistry of Phosphorus. 134. On the Triphosphanes H(t-BuP)₃H' Li(t-BuP)₃Li, and Me₃Si(t-BuP)₃SiMe₃ The reaction of 1,3-diiodo-1,2,3-tri-tert-butyltriphosphane, I(t-BuP)₃I, with lithium aluminium hydride leads to 1,2,3-tri-tert-butyltriphosphane, H(t-BuP)₃H ( 1 ). 1 reacts with n-butyllithium to 1,3-dilithium-1,2,3-tri-tert-butyltriphosphide, Li(t-BuP)₃Li ( 2 ), which reacts further with trimethylchlorosilane yielding 1,3-bis(trimethylsilyl)-1,2,3-tri-tert-butyltriphosphane, Me₃Si(t-BuP)₃SiMe₃ ( 3 ). The triphosphanes 1, 2 and 3 could be isolated in a pure state. In solution 1 forms the threo, threo and the threo,erythro configurated diastereomers 1a and 1b in a ratio of about 2:1. 3 predominantly exists in form of the threo,erythro configurated diastereomer 3b by steric reasons.     

2,3‐Diaryl‐3‐hydroxy­propionic acid inter­mediates in the synthesis of threo forms of 1,2‐diaryl‐1,3‐propane­diols

Racemic threo‐3‐hydroxy‐2,3‐diphenyl­propionic acid, C₁₅H₁₄O₃, (I), crystallizes from ethyl acetate as a conglomerate of separate (+)‐ and (−)‐crystals. The geometries of (I) and its methyl ester are compared. Reduction of (I) gives threo‐1,2‐diphenyl‐1,3‐propane­diol. The synthesis of threo forms of 1,2‐diaryl‐1,3‐propane­diols via 2,3‐diaryl‐3‐hydroxy­propionic acids is discussed.     

Enantioselective Reduction of Prochiral Ketones Using a Reagent Prepared from Lithium Aluminium Hydride, (+)Threo-1,16-Dibenzyloxy, 7(R),8(R)-Dihydroxy Hexadecane and Alcohol

Asymmetric reduction of prochiral ketones to optically active chiral secondary alcohols was achieved using a reagent prepared by modifying lithium aluminium hydride with a chiral auxiliary, (+)threo-1,16-dibenzyloxy,7,8-dihydroxy hexadecane and various additive alcohols. (+)threo-1,16-dibenzyloxy,7(R),8(R)-dihydroxy hexadecane was prepared from (+)threo-9(R),10(R),16-trihydroxy hexadecanoic acid. Alcohols such as CH₃(CH₂)_n-OH of different chain length (n = 0–11) and (R)-hydnocarpic alcohol were used. Complex prepared from (+)threo-1,16-dibenzyloxy,7(R),8(R)-dihydroxy hexadecane, LAH and (R)-hydnocarpic alcohol reduced acetophenone in moderate enantioselectivity (maximum of 70% ee). Various arylalkylketones were reduced with the same complex.     

Synthese ceramidähnlicher Verbindungen

Zusammenfassung Bei der Synthese vondl-threo-1-Hydroxy-2-N-lignoceryl-3-O-acetyl-4-cis-octadecen werden folgende Verbindungen erstmalig dargestellt:dl-threo-1,3-Dihydroxy-2-N-lignoceryl-4-cis-octadecen,dl-threo-1-O-Trityl-2-N-lignoceryl-3-hydroxy-4-cis-octadecen unddl-threo-1-O-Trityl-2-N-lignoceryl-3-O-acetyl-4-cis-octadecen. In gleicher Weise wurden die dazu analogen Verbindungen synthetisiert, die durch einen Myristoylrest an Stelle des Lignocerylrestes substituiert sind. Zu Vergleichszwecken wird auch dasdl-threo-1,3-Dihydroxy-2-N-lignoceryl-4-cis-octadecen dargestellt. Die Konstitution der Verbindungen wurde durch die IR-Spektren bestätigt.Mit 1 Abbildung.Prof. Dr. Dr. h. c.Friedrich Wessely-Karnegg zum 70. Geburtstag mit den besten Wünschen.1. Mitt.: Mh. Chem.98, 373 (1967).     

Simultaneous determination of epimers (+)-catechin and (‒)-epicatechin in Onosma bracteatum Wall. using high-performance thin-layer chromatography‒mass spectrometry method

High-performance thin-layer chromatography‒mass spectrometry (HPTLC‒MS) method was developed for the estimation of epimers (+)-catechin (CA) and (‒)-epicatechin (ECA) in Onosma bracteatum Wall. Resolving these epimers is challenging and so method optimization was done for the selection of the stationary phase and the mobile phase to achieve their coherent separation. To further increase the reliability of the obtained densitometric results, HPTLC–MS analysis was performed. The genus Onosma L. is a species-rich genus that exhibits complex patterns of morphological and karyological diversity, and highly debatable taxonomic approaches. Thus, many similar species are described based on morphological differences and often quite ambiguous. To facilitate the identification of O. bracteatum, separation was achieved using pre-coated silica gel 60 F₂₅₄ HPTLC plate as the stationary phase and a mixture of diisopropyl ether–ethyl acetate–formic acid (9.0:0.2:0.7, V/V) as the mobile phase for the separation of epimers CA and ECA. Sample preparation, mobile phase selection and optimization were given importance to manage good resolution (R_F) of these markers. Flavan-3-ols CA and ECA were identified and confirmed on the basis of R_F and in situ UV and MS overlaid spectra with respective standards. The method was validated for linearity, inter-day precision, intra-day precision, repeatability, accuracy, specificity, limit of detection, and limit of quantification. The average recoveries for epimers CA and ECA from ethyl acetate extract fraction (MEF) were found 98.86 and 99.03% indicating the good reproducibility for each marker. The proposed validated HPTLC method is simple, accurate and reproducible and is the first report on the separation and quantification of the epimers CA and ECA in O. bracteatum using HPTLC–MS.

     

Sphingolipide, 1. Mitt.: Synthese ceramidähnlicher Verbindungen

Zusammenfassung Im Zuge der Synthese vondl-threo-1-Hydroxy-2-N-myristoyl-3-O-acetyl-4-trans-octadecen werden folgende Verbindungen erstmalig dargestellt:dl-threo-1,3-Dihydroxy-2-N-myristoyl-4-trans-octadecendl-threo-1-O-Trityl-2-N-myristoyl-3-hydroxy-4-trans-octadecen unddl-threo-1-O-Trityl-2-N-myristoyl-3-O-acetyl-4-trans-octadecen. Die Konstitution wurde durch die IR-Spektren bestätigt. Die Synthesen vondl-threo-1,3-Dihydroxy-2-amino-4-octadecin unddl-threo-1,3-Dihydroxy-2-amino-4-trans-octadecen wurden verbessert. Die Massenspektren der letzteren werden beschrieben.Mit 4 Abbildungen     

Isomerisation of Erythro‐ and Threo‐Succinyl Units in Alternating Alkene‐Maleic Acid Copolymers: A Promising Route to New Microstructures

Summary: A first route to the isomerisation of erythro‐ and threo‐2,3‐disubstituted succinyl units in alternating alkene‐maleic acid copolymers is presented. The isomerisation reactions of the disodium salt of ethene‐maleic acid copolymer were carried out in aqueous solution at 180–240 °C in an autoclave. It is demonstrated that the erythro‐content can be changed from 17% up to 67%. The dissociation of methine C H bonds with the intermediate formation of a sp² hybridised carbon is proposed as the mechanism.

Isomerisation equilibrium between the threo‐ and erythro‐form of the 2,3‐disubstituted succinyl unit.     

17‐Oxo‐5α‐androstane‐3α,4β‐diyl diacetate and 17‐oxo‐5β‐androstane‐3α,4β‐diyl diacetate

The title compounds, both C₂₃H₃₄O₅, are the 5α and 5β configurations of two diacetate epimers. The 5β‐diacetate crystallizes in an hexagonal structure, unusual for steroid molecules. The unit cell has an accessible solvent volume of 358 ų, responsible for clathrate behaviour. The 5β‐epimer also features some shorter than average bond lengths in the 3α,4β‐acetoxy groups. The conformations of the molecules of both epimers are compared with those obtained through abinitio quantum chemistry calculations. Cohesion of the crystals can be attributed to van der Waals and weak molecular C—H⋯O interactions.     

Di-isotacticity of poly(methyl propenyl ether) and double-bond opening of methyl propenyl ether in cationic polymerization

The di-isotacticity of poly(methylpropenyl ether) obtained by the cationic polymerization has been studied by NMR spectra. The NMR spectra of β-methyl protons of the polymer are decoupled from the β-methine proton spectra to determine the di-isotactic fraction in a polymer. The signals of β-methyl protons at 8.78 and 8.89 τ are estimated as spectra based on threo- and erythro-di-isotactic diads, respectively. With BF₃·O(C₂H₅)₂ as a catalyst, the trans monomer yields a crystalline polymer and its structure is threo-di-isotactic. Otherwise, cis monomer produces an amorphous polymer, and it is a mixture of threo- and erythro-di-isotactic structure. From these results, it is concluded that the double bond in trans monomer is opened exclusively in the cis type, and in cis monomer cis- and trans-openings take place at almost the same rate.     

Synthese von threo-cis/threo-trans- und erythro-cis/erythro-trans-Dihydropalustrin. 17. Mitteilung über Schachtelhalmalkaloide

Synthesis of threo-cis/threo-trans- and erythro-cis/erythro-trans-dihydropalustrin The first synthesis of a threefold protected spermidine, namely ³-benzyloxycarbonyl-N¹-phthaloyl-N²-tosylspermidin ( 9 ) is presented. Each of the protecting groups can be removed selectively. After hydrazinolysis the resulting N³-benzyloxy-carbonyl-N²-tosylspermidine ( 10 ) has been condensed with methyl (2 E)-cis-7,8-epoxy-2-decenoate to the threo-cis/trans piperidines 17 , and with methyl (2 E)-trans-7,8-epoxy-2-decenoate to the erythro-cis/trans piperidines 17 , respectively. After catalytic removal of the Z group, the resulting aminoesters 13 and 18 , in a melt with imidazole, underwent ring closure to the 13-membered lactames 14 and 19 , respectively. reductive deprotection of the N-tosyl group with sodium/ammonia led to the stereoisomeric palustrines 15 and 20 , respectively.     

Improving the Cβ Stereoselectivity of l-Threonine Aldolase for the Synthesis of l-threo-4-Methylsulfonylphenylserine by Modulating the Substrate-Binding Pocket To Control the Orientation of the Substrate Entrance

l -Threonine aldolase from Actinocorallia herbida (AhLTA) is an ideal catalyst for producing l -threo-4-methylsulfonylphenylserine [(2S,3R)- 1 b ], a key chiral precursor for florfenicol and thiamphenicol. The moderate C_β stereoselectivity is the main obstacle to the industrial application of AhLTA. To address this issue, a combinatorial active-site saturation test (CAST) together with sequence conservatism analysis was applied to engineer the AhLTA toward improved C_β stereoselectivity. The optical mutant Y314R could asymmetrically synthesize l -threo-4-methylsulfonylphenylserine with 81 % diastereomeric excess (de), which is 23 % higher than wild-type AhLTA. Molecular dynamic (MD) simulations revealed that the mechanism for the improvement in C_β stereoselectivity of Y314R is due to the acylamino group of residues Arg314 controlling the orientation of substrate 4-methylsulfonyl benzaldehyde ( 1 a ) in the active pocket by directed interaction with the methylsulfonyl group; this leads to asymmetric synthesis of l -threo-4-methylsulfonylphenylserine. The success in this study demonstrates that direct control of substrates in an active pocket is an attract strategy to address the C_β stereoselectivity problem of LTA and contribute to the industrial application of LTA.     

Convenient Entry to α‐Amino‐β‐hydroxy‐γ‐methyl Carboxylic Acids. Diastereoselective Formation and Directed Homogeneous Hydrogenation of 3‐(3‐Aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐1,4‐benzodiazepin‐2‐ones

Aldol reaction of 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one ( 1 ) with 4‐substituted α‐methylcinnamaldehydes 2 – 5 afforded a mixture of threo‐ and erythro‐3‐(3‐aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐ones 6 – 13 . The chromatographically separated threo diastereoisomers 6, 8, 10 , and 12 and erythro diastereoisomers 7, 9, 11 , and 13 were submitted to ‘directed' homogeneous hydrogenation catalyzed by [Rh^I(cod)(diphos‐4)]ClO₄ (cod=cycloocta‐1,5‐diene, diphos‐4=butane‐1,4‐diylbis[diphenylphosphine]. From the erythro‐racemates 9, 11 , and 13 , the erythro,erythro/erythro,threo‐diastereoisomer mixtures 16 / 17, 20 / 21 , and 24 / 25 were obtained in ratios of 20 : 80 to 28 : 72 (HPLC), which were separated by chromatography. From the threo racemates 8, 10 , and 12 , the threo,threo/threo,erythro‐diastereoisomer mixtures were obtained in a ratio of ca. 25 : 75 (¹H‐NMR). The relative configurations were assigned by means of ¹H‐NMR data and X‐ray crystal‐structure determination of 21 . Hydrolysis of 21 afforded the diastereoisomerically pure N‐(benzyloxy)carbonyl derivative 27 of α‐amino‐β‐hydroxy‐γ‐methylpentanoic acid 26 , representative of the novel group of polysubstituted α‐amino‐β‐hydroxycarboxylic acids.     

Asymmetric synthesis of the natural erythro-(1R,2S)-8-O-4′-neolignan myrislignan

Abstract  

An efficient and practical asymmetric synthesis of erythro-(1R,2S)-8-O-4′-neolignan myrislignan was achieved by using vanillin and pyrogallic acid as the starting materials. Two key steps are involved: preparation of an enantiopure threo alcohol of predictable stereochemistry by dihydroxylation with AD-mix-β, and inversion of the absolute configuration from the threo to the erythro isomer using a Mitsunobu reaction. The route illustrates a new methodology for the synthesis of erythro-8-O-4′-neolignan.     

Fluoro-α-amino acids. 1—use of 19F NMR spectroscopy for the configurational determination of β-fluoro-α-amino acids through complexation by 18-crown-6 ether

Erythro and threo configurational assignments have been made for 11 β-fluoro-α-amino acids or esters using the effect of complexation of the ammonium group by 18-crown-6 ether on the ¹⁹F NMR parameters. For the erythro configurations, ³J(HF) increases and a high-field ¹⁹F chemical shift is generally observed; these phenomena are accompanied by a decrease in ³J(HH) and ³J(CF). The opposite effects are observed for the threo configurations. These observations can be explained by a change in the relative population of the conformers around the Cα-Cβ bond on complexation of the ammonium group. This complexation impairs the interactions between the ammonium and fluorine groups and, concomitantly, the steric hindrance between the ammonium and R (methyl, phenyl or carboxylate) groups is increased.