Search

The reaction between 2-phenylthiobenzhydrazide and aldoses has been investigated; the products obtained in these reactions have the structure of 2-polyhydroxyalkyl-Δ4-1,3,4-thiadiazolines as shown by spectroscopic evidence and by single crystal X-ray analysis

Asymmetric reactions on chiral bis (diphenylphosphine) metal complexes having C2 symmetry axis of the chelate ring obey the simple stereochemical rules which establish a relationship between the product configuration and complex conformation. The stereochemical basis of the application of this rule has been studied on the example of the cross-coupling reaction of crotyl alcohol derivatives and arylmegnesiumbromides on trans-bis-1S,2S- and trans-bis-1R,2R- (diphenylphosphino)cyclopentanenickel dibromide (NiBr2 ((SS)-dpcp) and NiBr2 ((RR)-dpcp)). Monitoring the reaction mixture by circular dichroism and 31P NMR spectroscopy shows that this reaction goes through Ni(Ph)Br(dpcp), NiPh2(dpcp) and Ni0(dpcp) intermediates. 31P NMR spectroscopy, just as CD, did not reveal the π-allyl (Y)Ni(dpcp) species (Y = leaving group of the crotyls). Probably, they take part in the reaction at a very small concentration. The observed effect of the influence of Y volume on the enantiomeric excess value of the reation was explained on the assumption of an equilibrium between two forms: in the one, the Ni in Ni(Y) (dpcp) is coordinated to the crotyl function, and in the other, Y is covalently bonded to the crotyl, with the Ni π-bonded to the crotyl double bond. Exchange of phenyl for 1-naphthyl group in ArMgBr is accompanied by a decrease of ee from 58% to 0%. Loss of enantioselectivity can be explained by attack of the bulky nucleophile from outside but not within the inner sphere of the complex as in the case of Ph. Major and minor diastereomers (8:1) of π-allyl(1-Np)Ni((SS)-dpcp) are not intermediates of this reaction but deadlock substances.

The thermal unfolding of cytochrome P-450 LIN and P-450 CAM measured in presence and absence of their specific substrates was analyzed by circular dichroism (CD) and the α-helix content was estimated. Both proteins show, independent of the presence or absence of the substrates, nearly the same amount of loss of the CD in the peptide region. The comparison of the half transition temperature determined from different chromophores and different methods indicates a non-two-state transition of the thermal unfolding. For such analysis we developed a new spectrometer, which is capable of measuring the CD simultaneously at all wavelengths in a limited wavelength region.

The thermal decomposition of spiro-1-pyrazolines 2 obtained by the cycloaddition of exocyclic α,β-unsaturated ketones with diazomethane gives spirocyclopropanes 4 with high selectivity and the new β-methyl-3-benzylidene derivatives 3. The configuration and conformation of the thermolysis products 3 and 4 were elucidated by different n.m.r. methods.

3-Hexulose phosphate synthase catalyzes the aldol reactions between D-ribulose 5-phosphate 1 and a rather wide range of aldehydes. The stereoselectivity of the reaction was investigated with propionaldehyde 3 as substrate. The sense of chirality at carbon atom 5 is definite, but two isomers at carbon atom 6 are formed during formation of the new CC bond.

Revision of previous work shows that PLE-cataiyzed hydrolysis of 1 leads to the (S)-alcohol 5 and not the (R)-alcohol 3 . However the homologue 2 gives the (R)-alcohol 4 .

The CD spectra Of some resorcylic acid macrocyclic lactones (RAL) are reported. The spectra Of the E,Z -isomeric ketones 1,6 are very similar in shape and magnitude. The Cotton effects Of the 7α-alcohols 2 and 7 are also Of the same shape, but the Δϵ values Of 7 are Only ca. 50% Of those Of the Others. The E-7β-Ol 3 gives a completely different CD, whereas in the Z-series 8 shows a similar CD curve as 6 and 7 , but with again reduced magnitude. The CDs Of the acetates 4 and 5 are very similar to those Of the corresponding alcohols 2 and 3 , resp. The effect Of the 7a- and 7β-hydroxy Or acetoxy group On the absolute conformation Of the “chain” from C(5) to C(10) is thus transmitted to the absolute value of the torsional angle Of the inherently chiral chromophore C(11)-C(12)-C(12a)-C(1a)-C(=0)O in 2,3 and 4,5 , resp. The CD spectra Of the E,Z -isomers do not exhibit straightforward correlation with the configuration around the C=C double bond.

Some oximes and oxime acetates of transoidal cholestenones have been synthesized. In three cases of stable syn/anti pairs of oximes both stereoisomers could be separated. The CD-spectra of all compounds have been measured. All syn-isomers show an additional CD band around 280 nm, which does not exist for anti-oximes.

Treatment of 2- O -benzoyl ( 1 ) and 2- O -acetyl ( 5 ) derivatives of benzyl 4,6- O -benzylidene-3- O -(2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl)-β- d -galactopyranoside under Zemplen conditions (catalytic amount of sodium methoxide in methanol) gave partially deacylated disaccharides in which the 2- O -acyl groups were retained. Likewise, a similar result was obtained with the β- l -rhamnopyranosyl analogue ( 3 ) of 1 . This anomalous reaction was used in a synthesis of the title trisaccharide ( 17 ) and of methyl 4,6- O -benzylidene-3- O -(2,3:4,6-di- O -isopropylidene-α- d -mannopyranosyl)-α- d -glucopyranoside, an intermediate for the synthesis of 2- O -glycosyl-3- O -(α- d -mannopyranosyl)- d -glucoses.

A new, very convenient and sensitive “in situ” method has been developed for the determination of the absolute configuration of chiral compounds, which can bind to the axial position of [Rh2(O2CCF3)4] (5) and induce circular dichroism within its electronic absorption bands. The CD spectra of the “in situ” complexes of chiral alcohols, ethers (including epoxides), olefins, and ketons with 5 show up to 5 Cotton effects (A – E) in the 600 – 300 nm range. This method works well for chiral secondary alcohols and monoolefins. For these compounds tentative rules are proposed, which correlate the absolute stereochemistry with the sign of certain Cotton effects of their complexes. A rule for the sign of band E for alcohols and a quadrant rule for the sign of band C for olefins can be applied. Olefins induce unexpected strong Cotton effects in presence of 5 giving evidence for a relatively stable π-bond between olefin and rhodium atom.

Some oximes of 4- and 6-ketosteroids, of des-A-5-keto-steroids, and the related compounds 31 and 33 have been synthesized. In three cases stable B / Z pairs are formed which could be separated. The CD-spectra of all compounds have been measured. The Cotton effects around 217 run of the 6-hydroxyimino-5α-steroids (1 – 18, 34, 36) are negative, those of the corresponding 4-analogues (20 – 23) are positive. A similar relationship holds for the des-A-steroidoximes 24 – 26 vs. 27, and the syn-oximes 34/36 vs. their anti-analogues 35/37. This Cotton effect can, therefore, be used for the determination of the configuration of such oximes. The Cotton effects below 200 nm do not always show similar regularities.

The first CD spectra of optically active ferricinium salts are reported. Cotton effects corresponding to the metal-ligand charge-transfer band have been observed for the compound with planar chirality.

Debaryomyces marama enantioselectively reduces p-Cl-benzophenone to the S-alcohol with high enantiomeric excess.

The 1 B 2u -band CD of siccanin ( 3 ) and some of its derivatives obeys the known rules for the benzene chromophore with the appropriate substitution pattern. The CD spectrum of the chromanone 8 is better resolved than that of related flavanones, the band between 300–320 nm is most probably the 1 B 2u -band of this chromophore. The non-planar styrenes 10–12 symmetrically substituted in the benzene ring with respect to the “pivot” bond follow Crabbe's rule, and the absolute configuration of siccanochromene-A ( 13 ) in the chromene ring follows from its CD to be S .

Resume Die zwei Phenylchromophore eines optisch aktiven 1,2-disubstituierten 1,2-Diphenylethans geben unabhangig voneinander Cotton-Effekte innerhalb des Wellenlangenbereichs der α-Bande. Durch Bildung der Summen-und Differenz-CD-Kurve fur ein threo/erythro Paar erhalt man CD-Spektren, die fur jedes “Halbmolekul” charakteristisch sind, und die im allgemeinen zwei 0-0—Linien um 37230 cm -1 aufweisen. Aus deren Vorzeichen kann die absolute Konfiguration an jedem der Chiralitatszentren eindeutig bestimmt werden.

The complexes of formula [CuSu 2 Am 2 * ] formed in situ from amino steroids (Am * ) and a methylene chloride solution of the complex [CuSu 2 Pr 2 ] (Su: succinimidate; Pr: isopropyl amine) show in the range of the d-d bands two Cotton effects at approx. 700 (Band I) and 600 nm (Band II), whose signs are correlated with the preferred torsion angle of the H 2 N-Cu moiety: a positive torsion angle leads to a positive CD-band I and to a negative CD-band II. These complexes form useful Cottonogenic derivatives of primary amino compounds.

The dicarboxylic acid 8 was synthesized from dibenzosuberone by dehydrogenation, reduction of the keto group and dicarboxylation. After resolution with cinchonine the (-)-enantiomer served as starting material for various transformation products with trans-configuration of the substituents at the 10,11-positions. Ring closure between these two groups led to the introduction of an additional homo- or heterocyclic ring. Attempted bromination of the dimethyl ester 9 of 8 gave the lactone 49 instead, LAH reduction of which resulted in formation of the corresponding ether bridge. Of both bridged compounds several derivatives have been prepared by modification of the substituent at C(11). Furthermore the products of nitration of the 5-keto derivatives 31 and 36 are described as well as some thio analogues and products containing one additional heteroring.

Three macrocyclic pyrrolizidine alkaloids have been isolated from the flowers of Crotalaria rosenii . Two of them , madurensine 1 and 7-acetylmadurensine 2 are rare but known alkaloids for which full spectroscopic data have been generated and some erroneous 13 CNMR data in the literature corrected. Crotaflorine 3, an alkaloid previously given a “probable” structure has been subjected to detailed spectroscopic analysis and shown too have structure 3. The recently introduced “COLOC” NMR technique has been used to distinguish between the two alternative structures 1 and 4.

Recently Dhar et al. reported the isolation of two new steroidal lactones from the leaves of Datura quercifolia HBK and formulated them as 5α,12α,17α-trihydroxy-1-oxo-6α, 7α-epoxy-22 S -witha-2,24-dienolide and 5α,17α-dihydroxy-1, 12-dioxo-6α,7α-epoxy-22 S -witha-2,24-dienolide on the basis of UV, IR, NMR and MS studies. Further detailed chemical and spectral studies have led to revised structures, namely 5α, 12α-dihydroxy-1-oxo-6α,7α: 24α, 25α-diepoxy-20 S , 22 R -with-2-enolide and 5α-hydroxy-1, 12-dioxo-6α, 7α: 24α, 25α-diepoxy-20 S , 22 R -with-2-enolide, respectively, for the above two compounds.

Bindentate complexes between [Mo 2 (O 2 CCH 3 ) 4 ] and suitable diols from the sugar series show Cotton effects around 500 to 450 (CD band I), 400 (II), 350 (III), and 300 nm (IV), and additional effects at still shorter wavelengths. The sign of Cotton effect IV is identical with the sign of the torsional angle HOCCOH for vic -diols. With this rule the absolute configurations of open-chain vic -diols of the threo -configuration and of vicinal primary-secondary diols can be determined with small amounts of substance; for the application of the rule the torsional angle(s) HOCCC should be fixed at 180°. Cotton effect III is only strong for vic -diols having a pyranose ring if no axial RO group is adjacent to the glycol moiety. Complexes of diols of pyranose structure carrying free hydroxyls at C-4 and C-6 show much smaller Δe values.

General interpretation of chiroptical characteristics of binding process of prochiral (Z) and chiral (Z ∗ ) 1,4-benzodiazepin-2-ones to human serum albumin (HSA) is presented. Interpretation of binding of Z studied by circular dichroism (CD) measurements allows us to conclude that the CD within the bands of bound Z is mainly due to the chirality of the first sphere and that the greatest part of 3 is bound in the M-conformation. For Z ∗ we conclude that ( S )-1 binds on both binding sites of HSA in the M-conformation, while ( R )-1 binds on two different binding sites in opposite conformations. Furthermore we conclude that binding via two nitrogens of the benzodiazepine, i.e. at two ends of the chromophoric system is rather more probable than via ring A.

The electronic transitions of the various chromophores of enol lactones 3a – 3e are assigned. The configuration at C-23 of the α-sulfanyl substituted lactones 3b – 3e is determined.

The 13C NMR signals for most of the carbon atoms of some 3,8″-biflavanoids could be assigned with the help of the spectra of the corresponding monomers. The CD spectra of such compounds containing one flavanone and one chalcone chromophore can be used to determine the absolute configuration.

The pH-dependence of the 1H NMR and Circular Dichroism (CD) spectra of 2-methylsuccinic acid was investigated. Both spectra undergo dramatic changes between pH 4 and 6, where both carboxylic groups become ionized. From the coupling constants of the tertiary proton with the assigned1 diastereotopic methylene protons, it is concluded that below pH 4 the syn-clinal (2) and above pH 6 the anti-periplanar (1) conformation of methylsuccinic acid prevail. The diesters of methylsuccinic acid also assume mainly the syn-clinal conformation (2). The pH-dependence of the CD spectra is discussed in terms of conformation and/or ionization effects.

(3 R ,4 R )- ( 1a ) and (3 S ,4 R )-tetrahydropyran-3,4-diol ( 2a ), and (2 R ,3 S )- ( 3a ) and (2 R ,3 R )-2-hydroxymethyltetrahydropyran-3-ol ( 4a ), derived from d -xylose, l -arabinose, d -glucose, and d -galactose, respectively, are structurally the simplest chiral carbohydrate-type precursors for bidentate ligands. The c.d. spectra of bidentate complexes between these diols and [Mo 2 (OAc) 4 ], as well as of the benzoates ( 1b–4b ) and tosylates ( 1c–4c ), and the copper(I) complexes ( 1d–4d ) of the diphenylphosphinites ( 1e–4e ) are discussed. The enantioselective reduction of acetophenone to S ( R )-1-phenylethanol with the complexes ( 10 and 11 , respectively) of the trans compounds 1a and 3a with lithium aluminium hydride has been studied. Low enantiomeric excess (⩽15%) was obtained, which was enhanced when an achiral modifier (ethanol, 2-propanol) was added to the complexes 10 and 11 prepared in situ . Enantioselective catalytic hydrogenation of Z -α-acetamidocinnamic acid was performed with the Rh(I)-norbornadiene complexes 2f and 4f , derived from the cis compounds 2a and 4a ; substantially lower enantiomeric excess ( S ( R )- N -acetylphenylalanine was achieved than with the analogous complexes 1f and 3f (∼90%). The results of the enantioselective reductions are discussed in the light of the conformational properties of 1a–4a and their congeners deduced from the c.d. spectra.

The CD of saturated iridoids containing a 2.9-dioxatricyclo[4.3.1.03,7] decan skeleton derived from valepotriates is determined by the acetal chromophore. For the less symmetric ring system of 1,6-anhydro hexapyranoses the sign of this CD is predictable. The vicinal effect for enones and diketones in this series is appreciable. A new rule for the correlation between the CD around 190–205 nm of enol ethers and their absolute conformation is given; the same reasoning is applicable to explain the known rules for cisoid and transoid vinyl cyclo-propanes.

8 pages, 1 scheme.-- PMID: 6658875 [PubMed]., Some new derivatives of norethisterone (17α-ethynyl-17β-hydroxyestr-4-en-3-one) are described in which the 17β-hydroxyl group of the steroid is esterified with polyunsaturated aliphatic acids. The potential of these compounds as long-acting contraceptive agents has been evaluated., The authors thank the Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, for financial support for this work.

Reductive radical cyclization of bromomethyl-silyl-ethers 1b and 2b was found to proceed in 5-exo-mode. Epimeric cyclic siloxanes 3 were transformed stereoselectively into 20(S) 25-hydroxycholesterol. Unsaturated (E) ester 4 was converted to its (Z) isomer 7 via saturation and selective dehydrogenation.

Grisan (Spiro[benzofuran-2(3H)1'-cyclohexane], 2 ) has been synthesized for the first time starting from cis-2-(2-hydroxybenzyl)-cyclohexanol ( 7 ).

Intramolecular para-ortho-coupling of the amide 4 to 7 was achieved by anodic oxidation in acetonitrile solution (containing 2% of methanol) in eighty % yield.

The leaves of Cassia floribunda afforded N 1 , N 8 -dibenzoylspermidine, physcion, 5,7′-biphyscion and 5,7′-physcion-physcionanthrone whose structures were determined by MS, 1 H and 13 C NMR spectral analysis as well as by chemical methods.

Modifications of protecting groups and of the oxidative coupling conditions lead to pure crystalline intermediates in the synthesis of galanthamine derivatives and gave dienone A in better yields than reported before. The E -configuration of amide 3′ in crystalline state has been determined by X-ray diffraction. Streptomyces affinis 6737 reduces A to the optically active (−)-epigalanthamine derivative C, whose absolute configuration was determined by Bijvoet's method. Nematospora corylii CBS 2608 reduces to racemic B. With Ashbya gossypii IFO 1355 a mixture of racemic B and optically active C is obtained. some other microbial transformations are described.

With the aid of one- and two-dimensional multipulse NMR techniques the structure of two novel sesquiterpene lactones from Achillea fragrantissima growing in Israel were elucidated and their conformational behaviour investigated. Although both compounds are closely related in their structures their CD spectra indicate that they belong to different enantiomeric series.

Zusammenfassung Am Beispiel des 2,3-Methylen-δ-caprolactons-(2S, 3S, 5S) (2) wird gezeigt, dass die Regel uber den CD der n → π* Bande von α,β-Cyclopropylketonen auf entsprechende Lactone ubertragen werden kann.

The CD within the 1 L b band of tetrahydroberberine alkaloids is rationalized with the aid of a rule taking into account the chirality of the second sphere, a sector rule for third (fourth, …) sphere contributions. Extension to the 1 L a , band CD is proposed. On this basis the absolute configuration of mecambridine, orientalidine, and chelidonine is determined. That of chelidonine has been proven independently by the kinetic method of partial resolution during esterification with α-phenylbutyric anhydride.

Zusammenfassung Die β,γ-ungesattigten A-homo-Δ1(2)-En-4-Ketosteroide zeigen die fur inharent dissymmetrische Ketone charakteristische Verstarkung des Cotton-Effektes (Homokonjugation). Es werden Reaktionen von A-homo-Steroiden beschrieben, die u.a. zur Darstellung des A-homo-5α-Androstans fuhren. Die Konformationen des ungesattigten und hydrierten Siebenringes in einigen A-homo-4-Ketosteroiden werden durch Messung des Circulardichroismus bestimmt und diskutiert.

Zusammenfassung Der Cotton-Effekt linearer Dienone folgt den Regeln fur einfache Enone, bei (annahernder) Koplanaritat der CG—Doppelbindungen steigt die Elliptizitat starker an. Cisoide Cyclohexenone zeigen einen positiven (negativen) Circulardichroismus, wenn die Doppelbindung in einem positiven (negativen) Octanten liegt. Bei Arylketonen, die formal gleichzeitig cisoide und transoide Doppelbindungen enthalten, erganzen sich die beiden dafur geltenden Regeln. Auf gekreuzt konjugierte Dienone ist die ubliche Octantenregel anwendbar, solange keine Gruppen mit interferierenden π- oder p -Elektronen vorliegen, ansonsten liefert die Regel uber transoide Enone das richtige Vorzeichen des Cotton-Effekts.

Zusammenfassung Der Circulardichroismus von an C-9 und C-10 stereoisomeren Steroid-3- und 6-ketone wird mit deren Konfiguration und Konformation in Beziehung gesetzt und die durch verschiedene Substituenten in Stellung 6 bzw. 3 bewirkte Anderung der Amplitude und sogar des Vorzeichens des Cotton-Effektes diskutiert. Die Stereochemie an C-9 kann nicht aus dem Circulardichroismus der 3-Ketone, wohl aber aus dem der 6-Ketone abgelesen werden; bei letzteren ergibt Epimerisierung an den C-Atomen 9 oder 10 jeweils eine konstante Verschiebung der Elliptizitat. Die 3,6-Diketone der A/B-cis-Reihe weisen eine starke Vicinalwirkung der CO-Gruppen auf, wahrend die Dichrogramme der A/B-trans-Verbindungen durch Superposition der Monoketon-Kurven erhalten werden konnen. Δ9- und Δ9(11)-19-nor-5β-Methyl-cholesten-Ketone zeigen einen ahlichen Cotton-Effekt wie die entsprechenden gesattigten Verbindungen mit 9α,10β-Konfiguration, die Δ1(10)-Doppelbindung beeinflusst dagegen die CO-Chromophore stark. Bie 9α,10β-Δ1-En-3-ketonen ist die Stereochemie an C-5 fur die Feinstruktur des Cotton-Effekts charakteristischer als seine Grosse.

Zusammenfassung Aus Kondurangin konnten nach vorsichtiger Saurehydrolyse Kondurangogenin A und ein Partialglykosid mit nur einem Dexosyzucker rein aber nicht kristallin erhalten werden. Aus dem Genin, das noch Zimtsaure und Essigsaure gebunden enthalt, liessen sich kristallisierte Derivate gewinnen, deren chemische und physikalische eigenschaften gestatten, fur Kondurangogenin A die Strukturformel eines 3β,11α,12β,14-Tetrahydroxy-5α,14β-pregnan-20-ons absuleiten, bei dem die beiden Sauren in 11,12-Stellung haften.

Spiro-pyrazoline-camphor and -borneol have been prepared from camphor. In these compounds and steroids with the same heterocyclic ring the azo group is optically active (Cotton effect at 330 mμ); the rotatory strength is unusually high for the ketonees. The CD of many 20-keto steroids with other hetero rings at 16,17-position (2-pyrazolines, oxazolines and isoxazolines) has been measured and correlated with the stereochemistry of the steroid side chain. The aromatic band system of the phenyl substituted isoxazoline steroids is also highly optically active. The CD of some azetidino and diazepino steroids is discussed.

Zusammenfassung Von 15α-Hydroxy-progesteron ausgehend wurden einige stereoisomere 15- und/ oder 20-Keto-pregnan-Derivate dargestellt und deren Circulardichroismus vermessen. Das 15, 20-Diketon zeigt bei normaler Stereochemie keine Vicinalwirkung, wahrend bei Isomerisierung in 14 und 17 eine gegenseitige Beeinflussung der Chromophore stattfindet. Die Einfuhrung einer 16β-Methylgruppe andert den Circulardichroismus der 20-Ketone vollig.

Rotations at the NaD line, CD and UV spectra of a series of O-alkyl alkylphosphonothioic acids, two alkylphenylphosphinothioic acids and their respective derivatives were measured. In the case of the phosphonothioic acid derivatives containing the PS bond the correct sign of rotation at the NaD line could be predicted by the application of Brewster's conformational asymmetry rule. A simple rule is given for correlating the sign of the Cotton effect around 200–230 nm with the configuration. In the CD spectra of the aromatic phosphinothioic acid derivatives at least four bands have been found whose assignments are discussed. The CD of the nondissociated acid (in nonpolar solvents) is analogous to that of homochiral ester derivatives; it is different in water solution, where the dissociated acid forms a new chromophore. According to the CD, the P(S)OH tautomeric form is preferred for the phosphono- and phosphinothioic acids.

The preferred conformations of the C-acetyl groups of 1,3-seco-2-norestran-4-one's were determined by the circular dichroism method at different temperatures. The experimental results agree with the predictions based on conformational analysis. At low temperature the mono and dibromo ketones (1c) and (3a) have a bromine atom syn-periplanar relative to the CO bond.

On the basis of chemical evidence and PMR spectral data a structure (empirical formula C21H29NO8) was ascribed to clivorine, an alkaloid isolated from Ligularia clivorum Maxim. In order to determine the configuration at C(3), C(4) and C(5) it was decided to carry out an X-ray analysis. (Author)

The vicinal effect between the keto groups of the two cholestane-4,7-diones epimeric at C-5 is small for the 5α-compound 3 , but appreciable for the 5β-isomer 2 . The synthesis and chiroptical properties of some lactones and lactames of 5-carboxy-5α-cholestane are described.

The C=N-group of azomethines shows a weak absorption band approximately at 250 mμ which is optically active when the chromophore is placed into an asymmetric environment. Correlations between the circular dichroism of some steroidal cyclic azomethines and their stereochemistry are discussed.