New enzymatic and chemical approaches to enantiopure etodolac

(+)- and (−)-etodolac enantiomers were prepared both by classical resolution via crystallisation of diastereoisomeric salts with (+) and (−)--methylbenzylamine, and by suitable manipulation of derivatives (−)-3- and (+)-4, obtained by lipase-catalysed kinetic resolution of racemic 3 X-ray diffraction analysis of the 4-bromobenzoate derivative of (+)-3, obtained from enantiopure acetate (+)-4, allowed us to determine the absolute (R) configuration of (−)-etodolac.     

Preparation of R- and S-mevalonolactones

(+)-Linalool has been converted into R(−)-mevalonolactone by a four-step procedure in 21 per cent overall yield. The final step introduces a new method for the fission of ---CO---CH₂---to ---CO₂H HO₂C---. (—)-Linalool similarly afforded S(+)-mevalonolactone. The absolute configuration of (+)- and (−)-linalools are established by this work as S and R respectively.     

The absolute configuration of trans-1,2-dimethylcyclopropane

By application of the newly discovered fact that 1° alkyl chlorides with γ-hydrogen form cyclopropanes on treatment with sodium metal, (−)-trans-1,2-dimethylcyclopropane has been prepared from (+)-1-chloro-2-methylbutane. Rigorous assignment of configuration to the isomeric cis- and trans-dimethylcyclopropanes is thereby achieved. The absolute configuration, (1R : 2R) trans-1,2-dimethylcyclopropane, can be assigned to the (−) enantiomer by several lines of argument and agrees with that calculated by Fitts.     

Total asymmetric syntheses of 3- and 4-deoxy-hexoses and derivatives

(1S,4S)-7-Oxabicyclo[2.2.1]hept-5-en-2-one ((−)-5, a “naked sugar”) has been converted to (−)-(1R,4S,6S)-6-endo-benzyloxy-2-bromo-7-oxabicyclo[2.2.1]hept-2-ene ((−)-12) in a highly stereoselective fashion. Double hydroxylation of the C=C double bond of (−)-12, followed by acetylation and Baeyer-Villiger oxidation of the resulting -acetoxyketone (−)-14 afforded (−)-5-O-acetyl-2-O-benzyl-3-deoxy-β-D-arabino-hexofuranurono-6,1-lactone ((−)-15). This compound was converted readily into (+)-methyl 3-deoxy--D-arabino-hexofuranoside ((+)-6 and (+)-methyl 3-deoxy-β-L-xylo-hexofuranoside ((+)-7) and partially protected derivatives. (−)-15 was also converted into 4-deoxy-D-lyxo-hexopyranose (34) and several partially protected derivatives such as (+)-methyl 4-deoxy-2,3-O-isopropylidene--D-lyxo-hexopyranoside ((+)-8).     

Total asymmetric syntheses of d-lividosamine and 2-acetamido-2,3-dideoxy-d-arabino-hexose derivatives.

The “naked sugar” (+)-(1R, 4R)-7-oxabicyclo[2.2.1]hept-5-en-one((+)-2) has been converted to D-lividosamine ((+)-1: 3-deoxy-D-glucosamine) and derivatives via (+)-2-chloro-2,3-dideoxy-5,6-O-isopropylidene-D-arabino-hexono-1,4-lactone ((+)-33) and (+)-2-azido-2,3-dideoxy-5,6-O-isopropylidene-D-ribo-hexono-1,4-lactone ((+)-34) in a highly stereoselective fashion. Similarly, 2-acetamido-2,3-dideoxy-D-arabino-hexose and derivatives were derived from the “naked sugar” (−)-(1S,4S-7-oxabicyclo[2.2.1]-hept-5-en-2-one ((−)-2) via the double hydroxylation of the C=C double bond in (−)-N-benzyl-N-[(1R,2S,4S)-6-bromo-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl] amine ((−)-40).     

Chemistry of the podocarpaceae—III A new lignan, seco-isolariciresinol and further constituents of the heartwood of Podocarpus spicatus

A new lignan for which the name seco-isolariciresinol is proposed, has been isolated from the heartwood of Podocarpus spicatus. The structure has been shown to be 2:3-bis(4′-hydroxy-3′- methoxybenzyl)-butan-1:4-diol (II, R = H), and confirmed by an absolute synthesis from (−)-matairesinol (I, R = H). A further examination of the extractives of the heartwood has resulted in the isolation of the minor constituents, (+)-taxifolin, (+)-aromadendrin, kaempferol and sequoyitol, in addition to the previously reported compounds, matairesinol, -conidendrin, quercetin, genistein and podospicatin.     

A new access to cyclopenta[c]pyridine ring system: syntheses of (−)-plectrodorine and (+)-oxerine

Total syntheses of (−)-plectrodorine [(−)-1] and (+)-oxerine [(+)-3] possessing the cyclopenta[c]pyridine ring system have been accomplished through a route starting from the chiral γ-butyrolactone 7 and exploiting the intramolecular oxazole–olefin Diels–Alder reaction. The sign of specific rotation for the synthetic (+)-3 was in disagreement with that reported for natural oxerine, leaving the absolute configuration of this monoterpene alkaloid incomplete.     

The absolute configurations of (+)-thalictrifoline and (+)-corydalic acid methyl ester. Total synthesis of (+)-thalictrifoline.

(+)-Thalictrifoline ($\text{3}$) has been synthesized from an optically resolved (+)-8-oxo-13-carboxytetrahydroprotoberberine ($\text{13}$) whose absolute configuration was established by correlation with (+)-$\text{18}$. This determines the absolute configurations of (+)-thalictrifoline ($\text{3}$) as 13R, 14R aria (+)-corydalic acid methyl ester ($\text{9}$) as 3R, 4R.     

番荔枝皂素(4S,5S)和(4S,5R)-Muricatacin的合成及Annonacin四氢呋喃段绝对构型的确证

本文以L-谷氨酸为原料合成了(1S,5S)和(4S,5R)-Muricatacin,并以该两化合物的NMR和[a]~D数据确证了Annonacin中四氢呋喃段的四个手性中心为(15R,16R,19R,20R).     

A general and highly efficient asymmetric synthesis of optically active anthracyclinones

The title asymmetric synthesis has been developed by featuring bromolactonization of (−)-acetals, derived from 2-acetyl-3,4-dihydronaphthacene-6,11-diones and (2R,3R)-(+)-N,N,N′,N′-tetraalkyltartaric acid diamides, as a key diastereoselective reaction. The produced bromolactone mixtures could be readily converted to the highly optically active key synthetic intermediates of 4-demethoxy- and 11-deoxy-4-demethoxyanthracyclinones.     

Synthese et configuration absolue de terpenes naturels: (+) uroterpenol, (+) et (−) α-bisabolols, (−) α-bisabololone

Stereoisomers of 8,9-epoxy p-menthene-1 have been synthetised and after separation their absolute configurations have been determined. From the (+)-epoxides we obtained isomers of (+)-uroterpenol and (+)-α-bisabolol. From the (?)-epoxides we obtained isomers of (?)-α-bisabololone. Natural (+)-and (?)-α-bisabolols are of configuration (4R, 8S) and (4S, 8R) respectively. Natural (?)-a-bisabololone has the (4S, 8R) configuration.     

Asymmetric 1,3-dipolar cycloaddition of chiral sulphinylethenes with 1-methyl-3-oxido-pyridinium and some nitrones

1,3-Dipolar cycloaddition of (R)-(+)-p-tolyl vinyl sulphoxide 1 with 1-methyl-3-oxidopyridinium 6 proceeded in a diastereoselective manner to afford the exo and endo cycloadducts 11a,b and 12a in 36%, 7% and 29% yield, respectively. The absolute configuration of 11a was determined by its transformation to (1S)-(−)-2-tropanol (−)-15. Attempts to the cycloaddition of the sulphinylethenes 17–19 with the pyridinium 6 were nsuccessful under several conditions. The reaction of the sulphoxide 20 with pyrroline 1-oxide 21 gave an inseparable mixture of products. The cycloaddition of 20 with 3,4,5,6-tetrahydropyridine 1-oxide22 afforded a mixture of four adducts in ca. 90% yield. High level of diastereoselectivity was achieved for the endo cycloaddition affording the adduct 23 in 33% isolated yield. The absolute configuration of 23 was confirmed by a single-crystal X-ray diffraction study. The stereochemical course of the reaction was discussed based on the absolute configuration of the products.     

Absolute Konfiguration der Equisetumalkaloide (+)-Palustrin,Palustridin ((+)-Monohydrochlorid) sowie der (−)-Dihydropalustraminsäure und weiterer Derivate. 16. Mitteilung über Schachtelhalmalkaloide

Determination of the absolute configuration of alkaloids from Equisetum sp.,e.g. (+)-palustrin, palustridin ((+)-hydrochloride), and (?)-dihydropalustramic acid and derivatives The absolute configuration of the title alkaloids has been determined using chiroptical methods (ORD., superposition of CD. values of appropriate models and a modified Horeau method). (+)-Palustrin is (13R, 17 S, 1′S)-17-(1-hydroxypropyl)-1,5,10-triazabicyclo [11.4.0]heptadec-15-en-11-on.     

Enzymatic resolution of 3-bromo-cyclohept-2-enol: application to the determination of the absolute configuration of diethyl (3-hydroxy-cyclohept-1-enyl)phosphonate

Enzymatic resolution of racemic 3-bromo-cyclohept-2-enol 2 with lipozyme affords enantiomerically pure (S)-(−)-2 whose absolute configuration was determined by chemical correlation, and further allowed an enantioselective synthesis of (S)-(+)-diethyl (3-hydroxy-cyclohept-1-enyl)phosphonate 1.     

The behaviour of some selenoglycollic acid derivatives in aqueous solutions and spectrophotometric determination of constants of the system Pd(II)/ethylene-bis- selenoglycollic acid

Interactions between ethylselenoglycollic, selenoglycollic and ethylene-bis- selenoglycollic acids and some “soft”, “borderline” and “hard” metallic ions have been studied. The interactions of [PdCl₄]_aq²⁻ with the three ligands were verified conductometrically and spectrophotometrically. The stability constants β₁ and β₂ for the system [PdCl₄]^2-- ethylene-bis-selenoglycollic acid have been determined at 25°C at ionic strength 3.0 M (NaCl). The stoichiometric ionization constant of the mentioned acid was also studied.     

Organoboranes for synthesis 17. Generality of hydroboration-amination for the conversion of terpenes into enantiomerically pure terpenylamines. Their utility for gas chromatographic analysis of chiral carboxylic acids

The generality of our new convenient synthesis of isopinocampheylamines by hydroboration-amination of -pinene has been established by converting representative terpenes into optically pure terpenylamines, such as (−)-cis-caran-trans-2-amine, (−)-cis-caran-trans-4-amine, (−)-longifolamine, and (+)-cis-myrtanylamine. The synthesis involves converting the terpene into the B-chloroditerpenylborane by treatment with chloroborane-methyl sulfide. This is treated with trimethylaluminum to form the B-methylditerpenylborane, and the latter is converted into the amine by treatment with hydroxylamine-O-sulfonic acid. cis-Myrtanylamine has been shown to be as effective as isopinocampheylamine for the gas chromatographic analysis of racemic carboxylic acids as their diastereomeric amides, suggesting the generality of this application of terpenylamines as chiral derivatizing agents.     

Asymmetric synthesis of N-aryl aziridines

The reactions of a variety of N-arylhydroxamates as nitrogen transfer reagents to acryloyl derivatives of (−)-8-phenylmenthol, (−)-quinine and (−)-Oppolzer's sultam acting as Michael acceptors was studied. Poor to modest diastereoselection was observed in the formation of aziridines. The absolute structure of one of the pure diastereomers secured from Oppolzer's auxiliary was established by X-ray crystallography and hence the absolute configuration of the derived methyl-N-phenylaziridine-2-carboxylate could be assigned. Whilst only poor facial selectivity was observed for chiral hydroxamic acid prepared from dehydroabietic acid, moderate to good enantioselection of aziridines could be achieved with the chiral quaternary salts based on cinchona alkaloids, especially with that of cinchonine. A model is presented to explain the origin of enantioselection and a mechanism is proposed for the aziridination reaction.     

The absolute configurations of (+)-usnic and (+)-isousnic acid. X-ray analyses of the (−)-α-phenylethylamine derivative of (+)-usnic acid and of (−)-pseudoplacodiolic acid,a new dibenzofuran,from the lichen Rhizoplaca chrysoleuca.

The absolute configuration of (+)-usnic acid has been shown to be (4aR) as in (1) by X-ray analysis of the (?)-α-phenylethylamine derivative (2). The structure and absolute stereochemistry of (?)-pseudoplacodiolic acid (4) have been established.     

Synthesis, stereochemistry, and circular dichroism of optically active o-substituted diphenyl sulphilimines and related compounds

Optically active o-substituted diphenyl N-substituted sulphilimines are readily synthesised by the reaction of the corresponding sulphides and t-butyl hypochlorite in the presence of l-menthol and amide anions. (−)-N-p-Tolylsulphonylsulphilimines (1, 2) obtained were converted to the corresponding (−)-N-unsubstituted sulphilimines (8, 9) by treating them with concentrated sulphuric acid. When (−)-S-o-anisyl S-phenyl N-(unsubstituted) sulphilimine (8) was treated with acylating agents or acrylonitrile, the corresponding optically active (−)-N-substituted sulphilimines were prepared with complete retention at sulphur. The absolute configuration of (−)-S-o-anisyl S-phenyl N-p-tolylsulphonylsulphilimine (1) was determined by converting it to (+)-S-o-anisyl sulphoxide (17). CD curves of (−)-o-substituted diarylsulphilimines exhibited a negative Cotton effect at around 270–285 nm, which was assigned to (S)-configuration at sulphur by comparing with the analogous sulphoxides. The substituent on the imino group of the sulphilimine gave no appreciable effect on the CD behavior and the lack of substituent effect was considered to be due to the semi-polar character of the S(IV)-N bond. Unusual effect of o-methoxy group on the CD curves was discussed in connection with solvent effect. Mechanism of this asymmetric synthesis has been investigated, and it has become apparent that the diastereomeric menthoxysulphonium chloride was an excess of (RR)-configuration was formed initially and the amide anion attacks the S atom of the salt with net inversion.