Synthesis and optical properties of asymmetric polyamides derived from cyclopropyl diacids and diamines

The polyamides were prepared from the dicarbonyl chloride of (+) (S)- or (?)(R)-trans-1,2-cyclopropanedicarboxylic acid (C3A) with either the dihydrochloride salt of (+)(S)- or (?)(R)-trans-1,2-diaminocyclopropane (C3B) or the dihydrobromide salt of (+)(S)- or (?)(R)-trans-1,2-bis(methylamino)cyclopropane (C3MB) by interfacial polycondensation. Several diamide model compounds composed of these monomers were also synthesized. The polyamides [poly(C3A-C3B)] derived from C3A and C3B have the capability of hydrogen bonding, while the polyamides [poly-(C3A-C3MB)] derived from C3A and C3MB do not. Poly(C3A-C3B) were insoluble in common organic solvents except strong acids. Poly(C3A-C3MB) were soluble in common organic solvents. Poly(C3A-C3B) had melting points higher than 300°C. Poly(C3A-C3MB) melted at 180–235°C. The ORD and CD study has shown that poly(+)C3A(+)C3B in methane sulfonic acid (MSA), 2,2,2-trifluoroethanol (TFE) (5 v % MSA), and tetramethylenesulfone (TMS) (5 v % MSA) exhibits a very strong Cotton effect or CD peak at 212–218 mμ, attributable to a component of the split π–π^* transition of the amide chromophores. Poly(+)C3A(+)C3MB in MSA and TFE (5 v % MSA) shows a strong Cotton effect or CD peak at 217–223 mμ and an intermediate Cotton effect or CD trough at 202–204 mμ as well as an intermediate Cotton effect or CD trough at 220–222 mμ and an intermediate Cotton effect or CD peak at 202–204 mμ in TFE and TMS. These peaks and troughs may be assigned to splitting of the π–π^* transition. The CD spectra of poly(+)C3A(+)C3MB in nonacidic media are quite different from those in acidic media: they are almost mirror images. The CD spectra in this transition induced by MSA suggests that a transition from a compact helix to another more extended helix with opposite handedness occurs similar to poly-L-proline I ? II. This transition may be explained by electrostatic repulsion between protonated amide groups. Viscosity data have shown that the conformation is changed to a highly extended from in acidic media. The polyamides and diamides derived from enantiomers exhibit mirror image spectra. Poly(+)C3A(+)C3B and poly(+)C3A(+)C3MB in every solvent studied exhibit a marked enhancement of the rotatory strength of ORD and CD with respect to the corresponding diamide models.     

Synthese und Chiralität der stereoisomeren Achillene,Achillenole und Hymentherene

(+)-cis-Achillene ( 10 ) and (?)-trans-achillenol (7), two monoterpenes recently isolated [1] from the essential oil of Achilleafilipendulina, were synthesized, together with their stereoisomers (?)-(9) and (+)-(8), starting from (S)-(+)-2,6-trans-dimethylocta-1,3, 7-triene ( 1 ). The isomeric ß-hymen thereties ((?)- 3 and (+)-4), often quoted [2] [3] [4] but never isolated, were obtained as intermediates. The mode of synthesis chosen establishesis (R)-chirality for naturally occurring (?)-trans-achillenol (7) and (+)-cis-achillene ( 10 ) as well as for the purely synthetic 4, 7-diene derivatives described in this paper.     

NMR studies and conformations of asymmetric polyamides derived from cyclopropyl diacids and diamines

The synthesis and optical properties of the polyamides [poly(C3A˙C3B) and poly(C3A-C3MB)] derived from asymmetric trans-1,2-cyclopropanedicarboxylic acids (C3A), asymmetric trans-1,2-diaminocyclopropanes (C3B), and asymmetric trans-1,2-bis(methylamino) cyclopropanes (C3MB) were reported in the preceding article. This paper describes the NMR studies and conformations of the polyamides. The NMR studies of the polyamides and their diamide models have suggested that the polyamides have about a 90° torsional angle for NH (or CH₃) CH. This angle seems to be reasonable because of less steric interaction, especially for poly(+)C3A(+)C3MB. The N? CH₃ of the poly(+)C3A(+)C3MB in sulfuric acid-d₂ (D₂SO₄) is a singlet and is tentatively assigned to trans to the carbonyl oxygen of the amide group. In 2,2,2-trifluoroethanol-d₃ (TFE-d₃) and chloroform-d (CDCl₃) it is also a singlet and is tentatively assigned to cis. The overall results obtained suggest that poly(+)C3A(+)C3MB exists in a compact helical conformation in TFE and TMS, while some conformational transition to a highly extended helical form with opposite handedness is induced by the addition of MSA. Likewise, poly(+)C3A(+)C3B must exist in some ordered conformation in the solvents studied. Possible ordered conformations of the polyamides have been proposed based on the experimental results and some assumptions.     

Biosynthese der Verrucarine und Roridine. Teil 5. Synthese von zwei Diastereoisomerenpaaren des [1,8-14C]-α-Bisabolols und Versuche zu deren Einbau in Verrucarol Verrucarine und Roridine, 32. Mitteilung [1]

The diastereoisomeric (+)-[1,8-¹⁴C]-(1'R,6R, S)-α-bisabolol ( 2a ) and (?)-[1,8-¹⁴C]-(1′S, 6R, S)-α-bisabolol ( 2b ) were synthesized by reaction of the Grignard compound of [1,6-¹⁴C]-5-bromo-2-methyl-2-pentene ( 12 ) with (+)-(R)- and (?)-(S)-4-acetyl-1-methyl-1-cyclohexene, ( 6a ) and ( 6b ) respectively. For the preparation of compound 12, cyclopropyl methyl ketone was treated with [¹⁴C]-methyl magnesium iodide to form the carbinol 11, which was cleaved by HBr. Compounds 6a and 6b were synthesized from (+)-(R)- and (?)-(S)-limonene, ( 4a ) and ( 4b ), via the derivatives 5a , 6a and 5b , 6b respectively. - This synthesis established the absolute configuration at C(1′) of the natural α-bisabolols: (R) for (+)-α-bisabolol and (S) for (?)-α-bisabolol. - Feeding experiments with cultures of Myrothecium roridum and radioactive (+)-(1′R, 6R, S)- and (?)-(1′S, 6R, S)-α-bisabolol ( 2a ) and ( 2b ) gave negative results. These findings indicate that bisabolane derivatives are not intermediates in the biosynthesis of verrucarol (3).     

Sesquiterpenoids from Costus Root Oil (Saussurea lappa CLARKE)

Apart from the well-known constituents (+)-β-selinene ( 2 ), (?)-β-elemene ( 4 ), (+)-β-costol ( 7 ), (?)-caryophyllene ( 17 ), and (?)-elemol ( 19 ) the following sesquiterpenoids have been isolated for the first time from costus root oil (Saussurea lappa CLARKE ): (?)-α-selinene ( 1 ), (+)-selina-4, 11-diene ( 3 ), (?)-α-trans-bergamotene ( 5 ), (?)-α-costol ( 6 ), (+)-γ-costol ( 8 ), (?)-elema-1,3,11 (13)-trien-12-ol ( 9 ), (?)-α-costal ( 11 ), (+)-γ-costal ( 12 ), (+)-γ-costal ( 13 ), (?)-elema-1,3,11 (13)-trien-12-al (elemenal, 14 ), (?)-(E)-trans-bergamota-2, 12-dien-14-al ( 15 ), (?)-ar-curcumene ( 16 ), and (?)-caryophyllene oxide ( 18 ). Compounds 6 , 8 , 9 , and 13 are new sesquiterpenoids. IR. and NMR. spectra of 12 sesquiterpenoids are reproduced.     

Über die absolute Konfiguration der Visnagane

(+)-cis-Khellactone methyl ether ( 4 ) and (?)-trans-khellactone methyl ether ( 6 ) had earlier been assigned the absolute configurations 3′-S; 4′-S and 3′-S; 4′-R, respectively, on the basis of the FREUDENBERG , rule. Both compounds together with their defunctionalised derivatives (?)- 7 and (+)- 8 (=(+)-lomatin), obtained from a mixture of (+)-visnadin ( 1 ) and (+)-samidin ( 2 ), were investigated by the HOREAU method. A conformational analytical study showed that the optical yield should rise in the order 4 < 6 < 7 , 8. This order was found and the α-phenylbutyric acid liberated was always dextrorotatory. The centre 3′ of the khellactones and their derivatives must be R-chiral and not S. Treatment of (?)- 6 with pyridinium perbromide gave (?)-trans-3-bromokhellactone methyl ether ( 11 ) as orthorhombic crystals. The X-ray crystal structure determination was made using the anomalous scattering of the Mo-K α radiation by Br. The result, — centre 3′ R-chiral (fig. g) — showed that the HOREAU method was correct.     

Assay of four stereoisomers of desacetyl diltiazem hydrochloride. Application toin vitro chiral inversion studies

Summary Direct resolution of four stereoisomers of the related compound of diltiazem hydrochloride, namely desacetyl diltiazem hydrochloride, was studied by both normal and reversed-phase chiral HPLC. The four stereoisomers were completely resolved on a Chiralcel OF column. The technique developed was applied to a chiral inversion study of desacetyl diltiazem hydrochloride. This inversion was observed neither in the solid state, in aqueous solution at 100°C for 3 h nor under visible light for 10h, but was observed in aqueous solution under UV irradiation.The (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride degraded with a half-life of 1.9 h in aqueous solution under UV and epimerized to (+)-(2R, 3S)-trans-desacetyl diltiazem hydrochloride. Similarly, (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride degraded about three times faster than diltiazem hydrochloride. Reverse epimerization of (+)-(2R, 3S)-trans-desacetyl diltiazem hydrochloride to (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride was not observed.The overall degradation was the result of two competitive processes, the epimerization and the decomposition of the benzothiazepin ring. The degradation and epimerization rate of (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride in solution under UV depended upon the solvent, the aqueous pH, and concentration.     

Photochemische Umsetzung von optisch aktiven 2-(1′-Methylallyl)anilinen mit Methanol

Photochemical Reaction of Optically Active 2-(1′-Methylallyl)anilines with Methanol It is shown that (?)-(S)-2-(1′-methylallyl)aniline ((?)-(S)- 4 ) on irradiation in methanol yields (?)-(2S, 3R)-2, 3-dimethylindoline ((?)-trans- 8 ), (?)-(1′R, 2′R)-2-(2′-methoxy-1′-methylpropyl)aniline ((?)-erythro- 9 ) as well as racemic (1′RS, 2′SR)-2-(2′-methoxy-1′-methylpropyl) aniline ((±)-threo- 9 ) in 27.1, 36.4 and 15.7% yield, respectively (see Scheme 3). By deamination and chemical correlation with (+)-(2R, 3R)-3-phenyl-2-butanol ((+)-erythro- 13 ; see Scheme 4) it was found that (?)-erythro- 9 has the same absolute configuration and optical purity as the starting material (?)-(S)- 4 . Comparable results are obtained when (?)-(S)-N-methyl-2-(1′-methylallyl)aniline ((?)-(S)- 7 ) is irradiated in methanol, i.e. the optically active indoline (+)-trans- 10 and the methanol addition product (?)-erythro- 11 along with its racemic threo-isomer are formed (cf. Scheme 3). These findings demonstrate that the methanol addition products arise from stereospecific, methanol-induced ring opening of intermediate, chiral trans, -(→(?)-erythro-compounds) and achiral cis-spiro [2.5]octa-4,6-dien-8-imines (→(±)-threo-compounds; see Schemes 1 and 2).     

Rogiolenyne D,the likely immediate precursor of rogiolenyne A and B,branched C15 acetogenins isolated from the red seaweed Laurencia microcladia of II Rogiolo. Conformation and absolute configuration in the whole series

It is shown that in the red seaweed Jaurencia microcladia, collected in the Mediterranean off the torrent Il Rogiolo, the new branched C₁₅ acetogenin rogiolenyne D ( = (+)-(2S,3S,7R))-3-(bromomethyl)-7-[(Z)-1-chlorohexen-3-en-5-nyyl)]-2-ethyl-2,3,6,7-tetrahydrooxepin; (+)- ?3 co-occurs with the already reported rogiolenyne A ((?)- 1 ) and B ((?)- 2a , suggesting the lineage (+)- 3 →(?)- 1 (?)- 2a ,Which is realized here chemically. The relative configurations are established via NMR analysis and chemical transformations as regards the seven-membered ring, while recourse is made to conformational analysis for the side chain. The absolute configuration is established via the Mosher's NMR method applied to the MPTA esters of (?)- 2a .     

Synthesis of(+)-(2S, 6S)-trans-α-Irone and of(-)-(2S, 6S)-trans-γ-Irone

A 3:1 mixture of (+)-(2S, 6S)-trans-α-irone ((+)-1) and (?)-(2S, 6S)-trans-γ-irone (?)-2) has been synthesized with ca. 70% e. e. by the ene reaction of (?)-(S)-3 and but-3-yn-2-one.     

Preparation and Absolute Configuration of Some Iris Essential Oil Constituents of the 5-methylsafranic-acid series

The β-dienoate (+)-(5S)- 13a (86% ee; meaning of α and β as in α- and β-irone, resp.) was obtained from (?)-(5S)- 9a via acid-catalyzed dehydration of the diastereoisomer mixture of allylic tertiary alcohols (+)-(1S,5S)- 15 /(+)-(1R,5S)- 15 (Scheme 3). Prolonged treatment gave clean isomerization via a [1,5]-H shift to the α-isomer (?)-(R)- 16a with only slight racemization (76% ee; Scheme 4). In contrast, the SnCl₄-catalyzed stereospecific cyclization of (+)-(Z)- 6 to (?)-trans- 8a (Scheme 2), followed by a diastereoselective epoxidation to (+)- 11 gave, via acid-catalyzed dehydration of the intermediate allylic secondary alcohol (?)- 12 , the same ester (+)- 13a (Scheme 3), but with poor optical purity (13% ee), due to an initial rapid [1,2]-H shift. The absolute configuration of (?)- 16a–c was confirmed by chemical correlation with (?)-trans- 19 (Scheme 4). ¹³C-NMR Assignments and absolute configurations of the intermediate esters, acids, aldehydes, and alcohols are presented.     

Synthesis of Enantiopure Chiral Perhydrobenzimidazole and Hexahydroquinoxaline Derivatives

 Starting from 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides and (R, R)-or (S, S)-trans-1,2-diaminocyclohexane, chiral C2-disubstituted perhydrobenzimidazole and trans-4a,5,6,7,8,8a-hexahydroquinoxaline derivatives were obtained depending on the polarity of the solvent.     

Preparation of optically active flowery and woody-like odorant ketones via Corey-Chaykovsky oxiranylation: Irones and analogues

α-, β-, and γ-Irones and analogues have been prepared from optically active ketones (+)- 1 , (+)- 6a,b , and (+)- 17 , via a Corey-Chaykovsky oxiranylation (Me₂S, Me₂SO₄, Me₂SO, NaOH) followed by isomerisation (SnCl₄ or MgBr₂). (+)-Dihydrocyclocitral ( 19a ), obtained from (?)-citronellal, and analogue (+)- 19b , were condensed with various ketones to afford (+)- 21a–f , and after hydrogenation (+)- 22a–f. A mild oxidative degradation of aldehydes (+)-trans-and (?)-cis- 8a,b , to ketones (?)- 16a,b , as well as olfactive evaluations, ¹³C-NMR assignments, and absolute configurations of the intermediate epoxides, aldehydes, and alcohols are presented.     

Circulardichroismus. 62. Mitteilung. Chiroptische Eigenschaften einiger Trimethylcyclohexen-Derivate: Die Jonone,Irone und Abszisinsäuren

The absolute configuration of (+)-α-ionone 3 (R), the absolute configurations at C(6) of (+)-cis-α-irone 5 (6S) and (?)-trans-α-irone 6 (6R), and the absolute configurations of (+)-cis-abscisic acid 10 (S) and (+)-trans-abscisic acid 11 (S) are deduced from the CD.-spectra.     

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.     

Synthesis of Enantiopure Chiral Perhydrobenzimidazole and Hexahydroquinoxaline Derivatives

Summary.  Starting from 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides and (R, R)-or (S, S)-trans-1,2-diaminocyclohexane, chiral C2-disubstituted perhydrobenzimidazole and trans-4a,5,6,7,8,8a-hexahydroquinoxaline derivatives were obtained depending on the polarity of the solvent. Received April 10, 2000. Accepted May 2, 2000     

Proof of the Absolute Configuration of (−)-(S)-2-Hydroxy-β-ionone by correlation with ursolic acid and with (−)-trans-verbenol

(?)-(S)-2-Hydroxy-β-ionone ( 33 ), (+)-(2 S, 6 S)-2-hydroxy-α-ionone ( 34 ), and their acetates 35 and 36 have been synthesized from (+)-(S)-6-methylbicyclo [4.3.0]-non-1-ene-3, 7-dione ( 3 ). The key intermediate (+)-(1 R, 3 S, 6 S)-2, 2, 6-trimethyl-7-oxobicyclo [4.3.0]non-3-yl acetate ( 7 ) was correlated with a degradation product of the pentacyclic triterpene ursolic acid ( 16 ). Compound 33 was also synthesized by an alternative route starting from (?)-trans-verbenol ( 42 ).     

Synthesis of the Bretonins,Polyolefinic Esterified Glyceryl Ethers of an Unidentified Sponge from the North-Brittany Sea: Absolute Configuration and Novel Structure Assignment

The absolute configurations of acetylated bretonin A (= (+}-( R )-1-[(acetoxy)methyl]-2-{[(4E,6E,8E)-dodeca-4,6,8-trienyl]oxy}ethyl 4-acetoxybenzoate; (?)- 1b ) and isobretonin A (= (+)-(S)-3-{[(4E,6E,8E)-do-deca-4,6,8-trienyl]oxy}-2-hydroxypropyl 4-hydroxybenzoate; (+)-2), previously isolated from an undetermined sponge of the North Brittany sea, were established by comparison with synthetic (+)- lb and (+)- 2 , obtained from the condensation of commerical (?)-(R)-2,2-dimethyl-1,3-dioxolan-4-yl p-toluenesuifonate ((?)-(R)- 15 ) with a mixture of (4E,6E,8E)- ( 14e ) and (4E,6Z,8E)-dodeca-4,6,8-trien-1-ol ( 14z ). This also allowed confirming the structure and configuration of bretonin B (= (S)-2-{[(4E,6Z,8E)-dodeca-4,6,8-trienyl]oxy}-1-(hydroxy-methyl)ethyl 4-hydroxybenzoate; 3 ) which was also isolated from the same sponge, albeit in a too small amount for a complete study. As concerns the glyceryl ethers precursors of the bretonins, co-occurrence of the usual (S)-con-figuration (from 1a ) with the unusual (R)-configuration (from (+)- 2 )) poses intriguing biogenetic problems.     

Preparation of chiral trans-5-substituted-acenaphthene-1,2-diols by baker’s yeast-mediated reduction of 5-substituted-acenaphthylene-1,2-diones

A series of trans-5-substituted-acenaphthene-1,2-diols were obtained in 21–72% yield with 97–100% ee by baker’s yeast-mediated reduction of the corresponding acenaphthylene-1,2-diones, in the presence of DMSO as a co-solvent and under vigorous agitation. The absolute configuration of (?)-trans-5-methoxy-acenaphthene-1,2-diol trans-3b and (?)-trans-5-bromo-acenaphthene-1,2-diol trans-3c was assigned as (S,S) and (?)-trans-5-thiomorpholin-acenaphthene-1,2-diol trans-3d was established as (R,R) by exciton-coupled circular dichroism.     

Circular Dichroism of Tricarbonyl(diene)iron Complexes. The Octant Rule Applied to Ketones Perturbed by Remote Fe(CO)3 Groups. Crystal Structure of (±)-Tricarbonyl[(1RS,4RS,5RS,6SR)-C5,6,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron

The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)- 7 ) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)- 8 ), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)- 11 ) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)- 12 ) are reported. The chirality in (+)- 7 and (+)- 8 is due to the Fe(CO)₃ moieties uniquely. The signs of the Cotton effects observed for (+)- 7 and (+)- 8 obey the octant rule (ketone n→π*_CO transition). Optically pure (?)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((?)- 10 ) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*_CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (?)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((?)- 2 ) and (?)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((?)- 3 ) and of the 3-denterated derivatives (?)- 5 and (?)- 6 are also reported. The CD spectra of the complexes (?)- 2 , (?)- 3 , (+)- 7 , and (+)- 8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)₃ moiety in (±)- 8 was established by single-crystal X-ray diffraction.