Syntheses of bile pigments. Part 15. First unequivocal assignment of the absolute configuration of an urobilinoid bile pigment by X-ray diffraction analysis of its synthetic precursor

(?)-(4S,16S)-8, 12-bis[de(2-carboxyethyl)]mesourobilin-IIIα hydrochloride ( 8 ) has been synthesized from the enantiomerically pure 1,4,5,10-tetrahydro-1-oxodipyrrin-9-carboxylic-acid precursor 6a whose absolute configuration was determined by X-ray diffraction analysis of the N-[(S)-1-(1-naphthyl)ethyl] carboxamide 7b . The present results prove unequivocally that an (S,S)-configurated urobilin chromophore displays a negative Cotton effect in the VIS absorption range. However, the helicity of the inherently dissymmetric chromophore remains undetermined.     

Conformational Studies of Marine Polyhalogenated α-Chamigrenes Using Temperature-Dependent NMR Spectra. Cyclohexene-ring flipping and rigid-chair cyclohexane ring in the presence of equatorial halogen atoms at C(8) and C(9)

Temperature-dependent NMR spectra indicate that the α-chamigren-3-ones (?) -11 , (+) -12 , (+) -14 (?) -15 , (+) -16, 18 , and 19 bearing equatorial halogen atoms at C(8) and C(9) undergo slow conformational flipping of the envelope-shaped enone ring, while the cyclohexane ring is maintained in the chair conformation. The α-chamigren-3-ols (+) -20 and (+) -21 , obtained by hydride reduction of (+) -12 , behave similarly, with slow half-chair inversion of the cyclohexenol ring. In each case, both conformers are about equally populated and detectable by NMR, except in the case of (+) -15 , where repulsive interactions between Br? C(2) and H_eq?C(7) make the population of the conformer 15b with Me—C(5) faced to H_ax?C(10) so low that it escapes direct ¹H-NMR detection. The energy barriers to these conformational motions are viewed to arise mainly from repulsive interactions between Me—C(5) and the axial H-atoms at C(8) and C(10), while, contrary to previous beliefs, no twist-boat conformations of the cyclohexane ring intervene. Similar conclusions hold for the 4,5-epoxides of both (?) -6 and (+) -7 . Clean Jones oxidatio of (?) -2 to 17 , where the CH₂?C(5) bond is maintained, and acid dehydration-isomerization of the α-chamigrene (+) -21 to the β-chamigrene (+) -24 , reflect the special stability of β-chamigrenes, providing a reason for their frequent occurrence in nature.     

Total Synthesis of (+)-(8S,13R)-Cyclocelabenzine

An asymmetric synthesis of the spermidine alkaloid (+)-cyclocelabenzine ( 1a ) and its (?)-(13S)-epimer 1b is described using optically active (+)-(3S)-3-amino-3-phenylpropionic acid as the chiral building block. The isoquinolin-1-one fragment 15 was synthesized by a modified Bischler-Napieralski reaction. The relative configuration of the (?)-isomer was determined by an X-ray crystal-structure analysis, which enabled us to determine the absolute configuration of natural (+)- 1a as (8S,13R).     

The Circular Dichroism of 5,6-Dimethylidene-2-bicyclo[2.2.n]alky Esters. Chiral Exciton Coupling between Benzoate and Exocyclic s-cis-Butadiene Chromophores

The optically pure aryl-substituted 5,6-dimethylidene-2-bicyclo[2.2.1]heptyl benzoates 12–21 were prepared; their UV absorption and CD spectra are reported. The (?)-(1S,2S)-esters 17–21 with carbonyl groups in endo-position exhibit typical excitonsplit Cotton effects whereas the corresponding (?)-(1S,2R)-esters 12 - 16 with carbonyl groups in exo-position do not present such effects. The chiral exciton coupling between the exocyclic diene and a remote p-substituted benzoate chromophore can be used for unambiguous assignment of the absolute configuration of 5,6-dimethylidene-2-endo-bicyclo[2.2.1]heptyl derivatives. The method is applied to establish the absolute configuration of 5,6-dimethylidene-2-exo and -2-endo-bicyclo[2.2.2.]octyl p-bromobenzoates (?)- 24 and (?)- 25 .     

First Optically Active Heptalenes and their Absolute Configuration

It is shown that dimethyl 7-isopropyl-5, 10-dimethylheptalene-1, 2-dicarboxylate ( 1 ) and dimethyl 5, 6, 8, 10-tetramethylheptalene-1, 2-dicarboxylate ( 2 ) can be resolved via the corresponding mono-acids and with the aid of optically active primary or secondary amines such as 1-phenylethylamine or ephedrine into the (?)-(P)- and (+)-(M)-enantiomeres, respectively. Characteristic for the (P)-chirality of the heptalene π-skeleton with C₂ or pseudo-C₂ symmetry are two (?)-CE's at the long wavelength region (450–300 nm) followed by at least one intense (+)-CE at wavelengths about or below 300 nm. The absolute configuration of the heptalenes was correlated with the well-established absolute configuration of (+)-(R)- and (?)-(S)-1-phenylethanol.     

Preparation and Absolute Configuration of (−)-(E)-α-trans-Bergamotenone

The synthesis, absolute configuration, and olfactive evaluation of (?)-(E)-α-trans-bergamotenone (= (?)-(1′S,6′R,E)-5-(2′,6′-dimethylbicyclo[3.1.1]hept-2′-en-6′-yl)pent-3-en-2-one; (?)- 1 ), as well as its homologue (?)- 19 are reperted. The previously arbitrarily attributed absolute configuration of 1 and of (?)-α-trans-bergamotene (= (?)-(1 S,6R)-2,6-dimethyl-6-(4-methylpent-3-enyl)bicyclo[3.1. 1]hept-2-ene; (?)- 2 ), together with those of the structurally related aldehydes (?)- 3a,b and alcohols (?)- 4a,b , have been rigorously assigned.     

Rogioldiol A,a new obtusane diterpene,and rogiolal,a degraded derivative,of the red seaweed Laurencia microcladia from II rogiolo along the coast of tuscany: A Synergism in Structural Elucidation

The structure of rogioldiol A ((?)- 1 ), isolated from the red seaweed Laurencia microcladia, was determined. Employing the exciton-coupling technique for rogioldiol A p-bromobenzoate ( 2 ), the absolute configuration at C(9) of (?)- 1 was assigned, and, together with extensive NMR experiments, the absolute configuration at C(10) and preferred conformations of (?)- 1 were determined. The absolute configuration of the hetero-substituted cyclohexane ring was deduced in analogy from the X-ray structure of 4 , a derivative of the aldehyde 3 , which was isolated from the same seaweed and is believed to be a degradation product of (?)- 1 .     

Totalsynthese und absolute Konfiguration von natürlichem Multifloramin

The diphenol 1 was resolved into its antipodes and their absolute configuration was established. The levorotatory isomer R-(?)- 1 was oxidized to the dienone R-(?)- 6 , which was rearranged to afford natural (?)-multifloramine (R-(?)- 7 ), thus establishing that the latter has the R-configuration. By the same reaction sequences, the enantiomeric diphenol S-(+)- 1 was transformed to provide (+)-multifloramine (S-(+)- 7 ) of the S-configuration.     

Heterotricyclodecane VIII. (−)-(1S, 3R, 6R, 8R)-2, 7-Dioxaisotwistan und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twistan; Synthese und Bestimmung der absoluten Konfiguration

A synthesis and the determination of the absolute configuration of (?)-(1S, 3R′ 6R, 8R)-2, 7-dioxa-isotwistane ( 13 ) and (?)-(1R, 3R, 6R, 8R)-2, 7-dioxa-twistane ( 14 ) is described. The results for 14 are compared with those for carboeyclic (+)-twistane ( 2 ) of known chirality.     

(+)-(1S, 3S, 6S, 8S)-und (−)-(1R, 3R, 6R, 8R)-4, 9-Twistadien: Synthese und Bestimmung der absoluten Konfiguration

(+)-(1S, 3S, 6S, 8S)-and (?)-(1R, 3R, 6R, 8R)-4, 9-Twistadiene: Synthesis and Absolute Configuration A synthesis and the determination of the absolute configuration of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-4, 9-twistadiene ((+)- and (?)- 4 , respectively) is described. Their chiroptical properties are compared with those of saturated twistane ((+)- and (?)- 5 ) as well as with those of the unsaturated and saturated 2, 7-dioxatwistane analogs (+)- and (?)- 9 , and (+)- and (?)- 10 , respectively, which also are compounds of known absolute configurations.     

Stereoselektive Synthesen von substituierten Tricarbonyl[tris(methylen)methan]eisen(0)-Komplexen

Stereoselective Syntheses of Substituted Tricarbonyl[tris(methylen)methan]iron(0) Complexes The complexes 3 , 9 , 10 , 22 , and 23 with one, two, and three Me substituents at the tris(methylen)methane moiety have been synthesized from the (acyloxy-1,3-diene)(tricarbonyl)iron(0) complexes 1 , 4 , 5 , 20 , and 21 , respectively, by ionic hydrogenation with BF₃ and Et₃SiH at ?78° in CH₂C1₂. These reductions are completely stereoselective, and their course can be predicted by assuming a dominant stereoelectronic control of the reaction. Formation of the carbocationic intermediates 11 from 4 and 12 from 5 , e.g., takes place only if the dissociating O? C bond is antiperiplanar to the donor C(β)? Fe bond. Fast H-transfer then converts the intermediate 11 to 9 and 12 to 10 . The configurations of 17 and 20 can be deduced from the structure of 22 and those of 18 and 21 from that of 23 . An X-ray structure determination of (1R,4S)camphanoate (?)- 13 derived from alcohol (?)- 7 confirms the configuration of 5 deduced above, The structures of the complexes 9 and 10 , 22 and 23 were determined by their unique NMR spectra. The diastereoisomeric complexes 6 and 7 have been synthesized from aldehyde 8 with MeMgI, the diastereoisomers 17 and 18 analogously from 16 or from methyl ketone 19 by reduction with LiAlH₄. Optically active starting materials (+)- 1 , (?)- 13 , (+)- 20 , and (+)- 21 gave, by ionic hydrogenation, the complexes (?)-(3R)- 3 , (+)-(2S,4S)- 10 , (?)-(R,R, S)- 22 , and (?)-(R,R,R)- 23 respectively, with known absolute configurations.     

Synthese des Dysidins

Synthesis of Dysidin The synthesis of dysidin ((?)- 1 ), the enantiomer of a metabolite of the marine sponge Dysidea herbacea, is described. To effect the synthesis, (±)-5-isopropyl-4-methoxy-3-pyrrolin-2-one ( 7 ) is converted to its lithium salt and reacted with (?)-(5R,2E)-3-methoxy-5-trichloromethyl-2-hexenoyl chloride ((-)- 11 ) to give (?)- 1 and its diastereoisomer (+)-5-epidysidin ((+)- 12 ) epimeric at C(5) of the pyrrolinone ring. The (?)-acyl chloride (?)- 11 has been synthesized from (+)-(R)-3-(trichloromethyl)butanoic acid ((+)- 8 ) via the intermediates (+)- 9 and (?)- 10 , the pyrrolinone 7 from N-benzyl-oxycarbonyl-L-valine via the intermediate 5 . The enantiomers of acid 8 have been resolved by fractional crystallization of their diastereoisomeric N-(1-phenylethyl)amides. The (R)-chirality of (+)- 8 was determined by comparing the ¹H-NMR spectra of the diastereoisomeric N-(1-phenylethyl)amides 16 and 17 , made from (+)- 8 by substituting deuterium for chlorine, with the spectra of the N-(1-phenylethyl)amides 14 and 15 of known absolute configuration. This correlation shows that literature value (R) for (?)- 8 is in error. Therefore, the structural formulae of (?)-dysidenin and (+)-isodysidenin, two other metabolites of D.herbacea, have to be changed to their mirror images as shown in formulae (?)- 3 and (+)- 4 , respectively.     

Absolute Configuration of 3-Substituted 1-Azabicyclo[2.2.1]heptanes

The l-azabicyclo[2.2.1]heptan-3-exo-ol ( 2 ) was resolved by fractional crystallisation of its hydrogen tartrate salts. The enantiomers (+)- and (?)- 2 were oxidised to the ketones (?)- 4 and (+)- 4 , respectively (Scheme). CD spectroscopy suggested that (?)- 4 possesses the (1R,4S)-configuration. This absolute configuration was confirmed by single-crystal X-ray diffraction of the derivative (+)-(1R,4R)-3-(1,3-dithian-2-ylidene)-1-azabicyclo [2.2.1]-heptane ((+)- 5 ).     

Über die Konstitution von Loroglossin. Vorläufige Mitteilung

The Constitution of Loroglossine. Loroglossine, a characteristic constituent of orchids, is shown to be bis-[4-(β-D -glucopyranosyloxy)-benzyl]-(2 R, 3 S)-2-isobutyl-tartrate ( 1 ). Hydrolysis and esterification gave 1 mol-equiv. of dimethyl (+)-2-isobutyl-erythro-tartrate ((+)-3) and 2 mol.-equiv. of a glucoside which, after acetylation, gave 4 , identical with a synthetic sample. The erythro configuration of (+)- 3 by oxidation of isobutyl-maleic acid with osmium tetroxide and subsequent esterification. The absolute configuration of (+)- 3 was based on Horeau experiments and NMR. data of the diastereomeric mixture of its esters 7 and 8 with S (+)- and R (?)-α-phenylbutyric acid respectively.     

The Preparation of Optically Pure 7-Oxabicyclo [2.2.1]hept-2-ene Derivatives. The CD Spectrum of (+)-(1R)-7-Oxabicyclo [2.2.1]hept-5-en-2-one

(?)-1-Camphanoyloxyacrylonitrile (=(?)-1-cyanovinyl camphanate; 1 ) obtained from the commercially available (?)-camphanoyl chloride and 2-oxo-propiononitrile added to furan at 20° in the presence of Cu (BF₄)₂ · 6H₂O or ZnI₂ and gave a mixture of 2-cyano-7-oxabicyclo [2.2.1]hept-5-en-2-yl camphanates ( 2–5 ) from which isomer 5 could be obtained pure by crystallization. The latter was transformed into (+)-(1R)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) in high yield and optical purity. Adducts 2–4 were recycled into 1 +furan by heating in toluene, and (?)-camphanic acid was recovered after saponification of 5 . The absolute configuration of 6 was deduced from its CD spectrum which showed two 1200-cm_?1 Franck-Condon series for its n→π transition.     

«Alkaloide» in tierischem und menschlichem Gewebe. 6. Mitteilung [1] [2]. Synthese und absolute Konfiguration chiraler 2, 3, 10, 11 - Tetrahydroxy-8-methyl-berbine [3]

Synthesis and absolute configuration of chiral 2, 3, 10, 11-tetrahydroxy-8-methylberbines [3] . The synthesis and absolute configuration of the four optically active berbines Xa, b and XIa, b are described. These compounds consitute potential ‘alkaloids’ obtained by condensation of either R-(+) or S-(?)-norlaudanosoline (THP, III) with acetaldehyde, a major metabolite of ethanol.     

Absolute Conformation and Configuration of (2S, 3S)-3-Acetoxy-5-(dimethylaminoethyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one Chloride (Dilthiazem Hydrochloride)

Resolution of racemic cis-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid ( 2 ) via the cinchonidine salt 3 , and brucine salt 4 , isolation of the calcium salts (+)- and (?)- 5 , as well as their cyclization to enantiomeric 1,5-benzothiazepines (+)- and (?)- 1 , are described. X-Ray single-crystal analysis reveals (2S, 3S) absolute configuration of (+)- 1 on the basis of tentative comparison of CD data with those for the 1,4-benzodiazepine derivative (+)- 8 of known absolute configuration.     

Crystal Structure of (−)-Corycavinium (+)-10-Camphorsulfonate,a biosynthetic intermediate to hexahydrobenzo[c]phenanthridine alkaloids

The crystal structure of (?)-corycavinium (+)-10-camphorsulfonate has been investigated by X-ray analysis. The structure of (?)-corycavinium ion ( ? (?)-(7S,13S,14R)-5,6,13,13a-tetrahydro-13a-hydroxy-7-methyl-2,3;9,10-bis(methylenedioxy)-8H-dibenzo[a,g]quinolizinium), has been determined. The conformation with B/C-cis-conjunction, a twisted half-chair of ring B , and a half-chair of ring C , as well as α-oriented substituted groups N…Me, C…Me, and C…OH is revealed. Feeding experiments with cell suspension cultures of Corydalis incisa (Papaveraceae) defined the intermediacy of (?)-corycavinium in the route from protoberberine-type to hexahydrobenzo[c]phenanthridine-type of alkaloids. On the basis of the present crystal conformation, the stereospecificity of the relating enzyme is biogenetically considered.     

Synthese von Haschisch-Inhaltsstoffen. 4. Mitteilung

(?)-Cannabidiol has been synthesized from (+)-cis- and (+)-trans-p-menthadien-(2, 8)-ol-(1) and olivetol, using N, N-dimethylformamide dineopentyl acetal or weak acids, such as oxalic, picric, or maleic acid, as catalysts. Since the chirality of (+)-trans-p-menthadien-(2, 8)-ol-(1) is known, the above synthesis constitutes an unambiguous prove for the absolute configuration of (?)-cannabidiol and the two isomeric (?)-6a, 10a-trans-tetrahydrocannabinols. If stronger acids, such as p-toluenesulfonic, trifluoroacetic, or hydrochloric acid, are used as mediators for the reaction, (?)-Δ⁸-6a, 10a-trans-tetrahydrocannabinol is obtained as the main product. Transformation of the thermodynamically more stable Δ⁸-tetrahydrocannabinol into the less stable Δ⁹-isomer was achieved in a practically quantitative yield by addition of hydrochloric acid and elimination of the elements of hydrochloric acid by means of potassium t-amylate. If resorcinols I were used instead of olivetol in the condensation reaction with strong acids, the corresponding homologues of Δ⁸-tetrahydrocannabinol were obtained in varying yields.     

Structure and biologicalactivity of demethyleneldelidine and its dihydro-<Emphasis Type="Italic">γ</Emphasis>-lactone

An excess of periodic acid was reacted with the diterpenoid alkaloid demethyleneldelidine (1) to produce a γ-lactone (2) in which the carbonyl at the C6-position was selectively reduced by an excess of NaBH₄. The conformation of the rings, configuration of asymmetric and spiro centers, and the nature of intramolecular H-bonds in the diterpenoid alkaloid demethyleneldelidine and its reduction product 3 were analyzed by an x-ray structure analysis. The spiro center at C10 in 3 had the S-configuration. The other asymmetric centers retained the absolute configuration characteristic of alkaloids with the lycoctonine carbon skeleton. The pharmacological properties did not change significantly despite the large difference in the carbon skeletons of γ-lactone 3 and starting 1.