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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

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.

The absolute configuration of the 2-(phenylmethyl) pyridine derivatives 1-9 had been established by X-ray diffraction and chemical correlation. Their CD spectra have been studied in different solvents for the free and protonated forms. It has now been found that, from the sign of the strong CD couplet between 270 and 220 nm, which was observable for all these compounds besides 7 and 9, their absolute configuration can be determined much quicker

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.

Chromic acid oxidation of manumycin (1), an antibiotic produced by Streptomyces parvulus (strain Tü 64), led to the isolation of 2-(2-methyl-4-oxo-2-pentenoylamino)-5,6-epoxy-1,4-benzoquinone (3) and (-)-(R)-2-methylhexanoic acid (4). From the absolute configuration of 4, determined by comparing its optical rotation with published data, follows the absolute configuration at the center of chirality in the diene side chain of manumycin (1) to be (6'R). Based on the direct comparison of the CD spectra of the two chromic acid oxidation products 2 and 3 with those of the antibiotic G7063-2 (5) and (-)-terreic acid (6) the stereochemistry at C-5 and C-6 of 1 was determined as (5R, 6S). From the negative CD-couplet of manumycin (1) its stereochemistry at C-4 was assigned as (4R).

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 chiroptical properties of the C(5)-epimeric 4,4-dimethyl-steroidderivatives 6, 7 and 8, recently prepared [1], are reported.

The absolute configurations of (+)-cantharic acid, a chiral derivative of the achiral insect defensive substance cantharidin (1), and of palasonin, a lower homologue of 1 occurring in the plant Butea frondosa, were shown to be represented by formulas 2 and 3, respectively (scheme 1). These results were obtained by application of the Horeau method (table 1) on the (+)-cantharic acid derivatives (+)-5, (−)-7, and (−) 11 (scheme 2), and the palasonin derivatives (+)-29 and (+)-30 (scheme 4), as well as by comparison of the chiroptical properties (tables 2 and 3) of a number of derivatives, prepared from either cantharic acid or palasonin. – Attempts to incorporate various radioactively labelled precursors into palasonin (3), using young and adult plants, have been so far unsuccessful.

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.

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.

The absolute configuration of dechlorogilmaniellin (2) could be determined from its chiroptical data by applying coupled-oscillator theory to the CD couplet around 272 nm and from the sign of its n π*Cotton effect. Gilmaniellin (1) has the same absolute configuration.

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.

Hydrogenation of the ketone group in di-O-benzylderivative (8) of the known macrocyclic lactone zeralenone (7) using a novel chiral borane complex 3. BH3, prepared in situ, proceeded at lower temperatures with moderate diastereoselectivity (∼40%, d. e. at −60°). Unsaturated diastereomers 9 and 10 were separated, and 9 converted into zeranol (11), a known anabolic agent. Restricted conformational mobility at lower temperatures is assumed for the intermediate 8 on the basis of the temperature-dependent CD spectra of its acetyl congeners 18 and 19. X-Ray structure analysis of 7-O-acetylderivative (13) of 11 revealed the (R)-configuration at C(7). Two crystallographically independent H2O molecules are involved in the H-bonds, one of them (O(21)) rises the helices of the molecules of 13 along b. Small positive torsional angle [C(16)-]C(161)-C(1) [=O] (+19.3°), transoid(E) conformation of the lactone group, and nearly achiral arrangement of the C(11)-C(12) bond (torsional angle [C(11)-]C(12)-C(121)[C(161)] is −93°) are the main conformational features that differentiate the macrocylic RAL (resorcinic-acid lactone) derivatives from the 6-membered lactone derivative 20, studied earlier by CD. Consequently, the rules developed for the CD effects within conjugation band (around 270 nm), and nπ* band (around 255 nm) of the latter compound, cannot be applied the macrocyclic lactones.

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 circular dichroism of keto derivatives with trichothecane skeleton and some of their rearrangement products has been measured. The sign (and sometimes even the magnitude) of all COTTON effects can be explained by applying the respective rules for the cyclohexanone, cyclopentanone, enone and ene-ester chromophores. Thus conformations could also be determined in those cases which did not follow unambiguously from conformational analysis. The conformation of the muconic acid moiety of the macrocyclic ring of verrucarin A is the same in dioxane solution as in the crystalline state.

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.

Zusammenfassung Mithilfe des Circulardichroismus und der optischen Rotationsdispersion wurde nachgewiesen, dass ein 2α-Halogen die “ubliche” Halbsesselform des Ringes A bei Δ4-En-3-ketosteroiden stabilisiert, ein zusatzliches 6β-Chlor fuhrt aber trotzdem zur Konformationsumkehr dieses Ringes. Die Konformation des Ringes A im 2,2,6β-Trichlor-testosteron wird diskutiert.

The CD of the N-nitroso derivatives of some Solanum spiroaminoketal alkaloids and some nitrogenous steroids as well as a number of non-steroidal amines have been measured. The nN → π3*-absorption band at 360–380 nm is optically active. A new sector rule for chromophores of the type XYZ↔XYZ is proposed, which correlates the stereochemistry of nitroso-amines, nitro compounds and lactones to their n → π*-Cotton effects.

A new pentacyclic triterpenoid, liquoric acid, has been isolated from the roots of Glycyrrhiza glabra L. as the methyl ester. Its properties are consistent with the formulation as a glycyrrhetic acid derivative containing an extra oxygen atom as an ethereal bridge, probably between the 16- and 21-positions.

– The circular dichroism of some non-conjugated unsaturated carbonyl compounds, which are conformationally mobile, has been measured at +20° and at about −178°. Specifically for the steroidal compounds 1 and 2 and the monocyclic aldehyde 14, their substituted analogs 4–6, 9–11, and 15–19, respectively, as well as for the aliphatic ketone 21 the CD. temperature gradients are interpreted in terms of the preferred conformations. In the case of the β,γ-unsaturated aldehydes 1 and 14, a correlation of these results with the photolytic decarbonylation from the excited singlet states is discussed.

The CD of many β-substituted adamantanones was measured in different solvents. Axial polar substituents, as COOR, Cl, Br, I, and N 3 show “anti-octant” behaviour. The CD of the fluoring compound consists of two nicely separate vibrational series of the same (“octant”) sign. The β-equatorial substituted halogeno-adamantanones (besides the fluoro derivative) posssess extraordinary high UV and CD absorption, which is due to an enhanced electric transition moment vector, and which can be correlated linearly with the polarizabilities of these substituents. The vicinal effects of some β-substituted adamantane-diones are found to be relatively small. The limitations of the octant rule are discussed on the basis of existin theories.

The conformation of the cyclopentenones 5 to 8 is determined from their CD-spectra. The site of enolization and the conformation of cis - and trans -isohumulone ( 1 and 2 ) is determined with the help of the CD-spectra, the direction of enolization for the humulinic acids 3 and 4 is tentatively determined by the same method.

Zusammenfassung Der Circulardichroismus mehrerer untersuchter 11-Ketoscteroid andert sich beim Abkuhlen auf −188° immer in Richtung zur Kurve des formal Enantiomeren. Ein Vorzeichen-wechsel wird nur dann beobachtet, wenn Δe max bei Zimmertemperatur relativ klein ist. Die Anderung der Elliptizitat mit der Temperatur wird auf ein Konformeren-Gleichgewicht des Ringes C zuruckgefurhrt.

Zusammenfassung Anhand eines sehr vereinfachten Modells fur den n → π*—Ubergang α,β-ungesattigter Ketone wird fur nichteben aufgebaute Enone eine Beziehung zwischen dem Schraubungssinn des Chromophors und dem Vorzeichen des Circulardichroismus abgeleitet. Diese ist auf 6- und 7-gliedrige Ringe anwendbar. Bei Cyclohexenonen mit koplanarer Anordnung des Enonsystems determiniert das aus der Ringebene herausragende C-Atom den Cotton-Effekt, wie empirisch gefunden wurde.

Zusammenfassung Es wurde die Abhangigkeit des CD von gesattigten und 16:17-ungesattigten 20-Ketosteroiden von der Substitution an C-12 untersucht. Die erhaltenen Daten stehen mit der Konformations-analyse dieser Verbindungen in Einklang. Die stabilste Konformation der Seitenkette in Δ 16 -Pregnen -3β-ol-20-on (transoides Enon, Carbonylsauerstoff oberhalb der Eben C-15, C-16, C-17, C-13) und seinen 12-Substitutionsprodukten wurde abgeleitet.