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).     

Optisch aktive 3-Amino-2H-azirine als Bausteine für enantiomerenreine α,α-disubstituierte α-Aminosäuren: Synthese des α-Methylphenylalanin-Synthons and Einbau in Modell-Peptide

Optically Active 3-Amino-2H-azirines as Synthons for Enantiomerically Pure αα-Disubstituted α-Amino Acids: Synthesis of the α-Methylphenylalanine Synthons and Some Model Peptides The synthesis of a novel 2-benzyl-2-methyl-3-amino-2H-azirine derivative with a chiral amino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers 9a and 9b (Scheme 4) which are the D - and L -2-methylphenylalanine ((α-Me)Phe) synthons, respectively. The reaction of 9a and 9b with thiobenzoic acid and with Z-leucine yielded the monothiodiamides 10a and 10b (Scheme 5) and the dipeptide derivatives 11a and 11b (Scheme 6), respectively. Methanolysis of 11b yielded 12b . The absolute configuration of 10a was established by X-ray crystallography. The absolute configuration of (α-Me)Phe in 12b has been deduced from the known configuration of L -leucine.     

Racematspaltung und Bestimmung der absoluten Konfiguration von 2, 6-disubstituierten Bicyclo [3.3.1]nonanen

Resolution and Determination of the Absolute Configuration of 2,6-Disubstituted Bicyclo[3.3.1]nonanes (±)-endo, endo-Bicyclo [3.3.1]nonane-2,6-diol was resolved via diastereomeric camphanic acid esters. Conversion of the (+)-enantiomer 2 via (+)- 5 and (+)- 6 as key intermediates gave (+) methyl 3-(3-oxocyclohexyl)-propionate ( 7 ) which independently could be prepared also from the known (+)-(R)-3-oxo-cyclohexane-carboxylic acid ( 8 ). These chemical correlations establish the absolute configuration of (+) -2 , (+) -5 and (+) -6 as well as that of (+)-bicyclo [3.3.1]nonane-2,6-dione ( 1 ) obtained by oxidation of (+) -2 . The chiroptical properties of 1 and 6 are discussed.     

Enantioselektive α-Alkylierung von Asparagin- und Glutaminsäure über die Dilithium-enolatocarboxylate von 2-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]essigsäure und 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionsäure

Overall Enantioselective α-Alkylation of Aspartic and Glutamic Acid through Dilithium Enolatocarboxylates of 2- [3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]acetic and 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionic Acid, respectively The pure methyl esters 10 of the heterocyclic carboxylic acids specified in the title were prepared in several steps by known methods from aspartic and glutamic acid, with overall yields of ca. 20%. The corresponding heterocyclic acids 11 were doubly deprotonated by LiNEt₂/BuLi or LiN(i-Pr)₂/BuLi to give enolatocarboxylates ( 3 ). The latter were reacted with electrophiles (MeOD, Mel, C₆H₅CH₂Br) to give the crystalline products 14 – 21 diastereoselectively. Hydrolysis of the imidazolidinone ring of three such products gave the corresponding α-branched aspartic and glutamic acids 22 – 24 of known absolute configuration, thus establishing the stereochemical course of the overall enantioselective alkylations.     

Zur Ermittlung der Konfiguration und Konformation von N-Glycosyl-3-carbamoyl-pyridinium-ionen. Eine Berichtigung zu [2]

Determination and configuration of N-glycosyl-3-carbamoylpyridinium ions. A correction . The work reported twenty years ago by one of us (M. V.) [2] has been reproduced and enlarged. In our previous communication we describe how the kinetics of the periodic oxidation of an anomeric pair of nucleosides would allow to assume the configuration and the conformation of the sugar part of the molecule, but our hypothesis was not confirmed by the ¹H-NMR. spectroscopy. In the present work we show that our point of view was and is definitively exact, but that N-α- and N-(β-D -glucosyl)-3-carbamoyl-pyridinium-ion have been involuntary confounded in the former publication.     

Synthese und Bestimmung des Chiralitätssinns von (+)-(R)-1-Azabicylo[3.3.1]nonan-2-on

Synthesis and Determination of the Chirality Sense of (+)-(R)-1-Azabicyclo[3.3.1]nonan-2-one Optically active (+)-(R)-1-azabicyclo[3.3.1]nonan-2-one ((+)- 1 ) of known absolute configuration is synthesized in the following way: Resolution of (±)-piperidin-3-ethanol ((±)- 2 ) by fractional recrystallization of its diastereoisomeric salts with (+)-3-bromocamphor-8-sulfonic acid from EtOH gave a less soluble salt that yielded(+)- 2 . The chirality sense of (+)- 2 was shown to be (R) by chemical correlation with the enantiomers of 3-oxocyclopentaneacetic acid ((±)- 8 ) of known absolute configuration. This correlation was effected by a Beckmann rearrangement of the oxime (R)-9 to the pyridone (S)- 10 followed by a direct reduction with LiAlH₄ to give the enantiomer (?)-(S)- 2 that was characterized as its benzyloxycarbonyl derivative (?)-(S)- 3 . The alcohol (+)-3 was converted via (+)- 4 into the nitrile (+)-5 which gave by hydrogenolysis and hydrolysis the (R)-configurated hydrochloride (+)- 6 which was cyclized to the bicyclic (5R)-lactam (+)- 1 in 67% yield by heating with 2 equiv. of dibutyltin(IV) oxide in toluene. The nonplanar amide function in (+)- 1 with the substituents at the N-atomarranged in a trigonal pyramid causes two rather intense Cotton effects at 242 (Δ?_max = +19.5) and 211 nm(Δ?_max = ?17.9) in the CD spectrum. If the molecules of (+)- 1 do exist mainly in the chair-twistboat conformation, the amide chromophore is pyramidally deformed in a sense defined by the absolute configuration at C(5). Therefore, the CD spectrum of the (5R)-lactam (+)- 1 can be used to test theories describing the chiroptical properties of distorted amides.     

Optisch aktive 3-Amino-2H-azirine als Bausteine für enantiomerenreine αα-disubstituierte α-Aminosäuren: Synthese von Isovalin-Synthonen und Einbau in ein Trichotoxin-A-50-Segment

Optically Active 3-Amino-2H-azirines as Synthons for Enantiomerically Pure αα-Disubstiuted α-Amino Acids: Syntheses of Isovaline Synthons and a Segment of Trichotoxin A-50 The synthesis of a novel 3-amino-2-methyl-2-[2-(phenylsulfonyl)ethyl]-2H-azirine derivative 12 with a chiral substituent at the amino group is described. Chromatographic separation of the diastereoisomer mixture gave pure diastereoisomers which, after an electrochemical cleavage of the phenylsulfonyl group, yielded the (S)- and (R)-isovalin (Iva) synthons 13a and 13b , respectively. The absolute configuration of the precursor molecule 12b was established by X-ray crystallography. The Iva synthons were successfully used in the synthesis of the C-terminal pentapeptide Z-Leu-Aib-(R)-Iva-Gln-Valol of the peptaibole Trichotoxin A-50 and its epimer.     

Resolution and absolute configuration of 1,2,3,5,6,10bβ-hexahydro-6α-phenylpyrrolo[2,1-α]isoquinoline (McN-4612-Z). A problem of determination of the enantiomeric purity for a tertiary amine

Details for the resolution of 1,2,3,5,6,10bβ-hexahydro-6α-phenylpyrrolo[2,1-α]isoquinoline (1) , a potent antidepressant-like compound, into its enantiomers with di-p-toluoyltartaric acid ( 2) are reported. Enantio-merically-enriched R-(+)-2-phenylpyrrolidine was transformed into enantiomerically-enriched 1 to determine enantiomeric purity and absolute stereochemistry for the resolved amines 1 . Thus, we ascertain that samples of (+)- and (—)- 1 with an enantiomeric purity of ≥99% were prepared, and that bioactive (+)- 1 possesses the 6S,10bR absolute configuration. The enantiomeric purity of ≥99% was confirmed by 360-MHz ¹H nmr examination of 1:1 diastereomeric salts formed from 1 or (—)- 1 and (+)-Mosher's acid (MTPA). The maximal optical rotation reported (ref 8) for (+)- 3 (100% o.p.) was shown to correspond to 100% e.e.     

Darstellung,Strukturen und EPR-Spektren der Rhenium(II)Thionitrosylkomplexe trans-[Re(NS)Cl3(MePh2P)2] und trans-[Re(NS)Br3(Me2PhP)2]

Preparation, Structures, and EPR Spectra of the Rhenium(II) Thionitrosyl Complexes trans -[Re(NS)Cl₃(MePh₂P)₂] and trans -[Re(NS)Br₃(Me₂PhP)₂] The paramagnetic rhenium(II) thionitrosyl compounds trans-[Re(NS)Cl₃(MePh₂P)₂] and trans-[Re(NS)Br₃(Me₂PhP)₂] are characterized by crystal structure diffraction and EPR spectroscopy. Trans-[Re(NS)Cl₃(MePh₂P)₂] is formed during the reduction of (a) [ReNCl₂(MePh₂P)₃] with disulphur dichloride or (b) of mer-[ReCl₃(MePh₂P)₃] with trithiazyl chloride. Trans-[Re(NS)Br₃(Me₂PhP)₂] is the final product of the ligand exchange reaction of mer-[Re(NS)Cl₂(Me₂PhP)₃] with bromine whereby the metal occurred to be simultaneusly oxidized. The crystal structure analyses show for trans-[Re(NS)Cl₃(MePh₂P)₂] (monoclinic, C2/c, a = 13.831(3) Å, b = 13.970(1) Å, c = 14.682(2) Å, β = 95.33(1), Z = 4) and trans-[Re(NS)Br₃(Me₂PhP)₂] (monoclinic, C2/c, a = 33.292(5) Å, b = 8.697(1) Å, c = 17.495(3) Å, β = 115.65(1), Z = 8) linear co-ordinated NS ligands (Re–N–S-angles 180° and 174.8°). The metal atom is octahedrally co-ordinated with the phosphine ligands in trans position to each other. X-band and Q-band EPR spectra of the rhenium(II) thionitrosyl complexes (5 d⁵ “low-spin” configuration, S = 1/2) are detected in the temperature range 295 ≥ T ≥ 130 K. They are characterized by well resolved ^185,187Re hyperfine patterns. The hyperfine parameters are used to get information about the spin-density distribution of the unpaired electron in the complexes under study.     

Darstellung,Kristallstrukturen, Schwingungsspektren und Normalkoordinatenanalyse der bindungsisomeren Chlororhodanoiridate(III) trans-[IrCl2(SCN)4]3− und trans-[IrCl2(NCS)(SCN)3]3−

Preparation, Crystal Structures, Vibrational Spectra, and Normal Coordinate Analysis of the Linkage Isomeric Chlororhodanoiridates(III) trans-[IrCl₂(SCN)₄]^3? and trans-[IrCl₂(NCS)(SCN)₃]^3? By treatment of Na₂[IrCl₆] with NaSCN in 2N HCl the linkage isomers trans-[IrCl₂(SCN)₄]^3? and trans-[IrCl₂(NCS)(SCN)₃]^3? are formed which have been separated by ion exchange chromatography on diethylaminoethyl cellulose. X-ray structure determinations on single crystals of trans-(n-Bu₄N)₃[IrCl₂(SCN)₄] ( 1 ) (monoclinic, space group P2₁/a, a = 18.009(4), b = 15.176(3), c = 23.451(4) Å, β = 93.97(2)°, Z = 4) and trans-(Me₄N)₃[IrCl₂(NCS)(SCN)₃] ( 2 ) (monoclinic, space group P2₁/a, a = 17.146(5), b = 9.583(5), c = 18.516(5) Å, β = 109.227(5)°, Z = 4) reveal the complete ordering of the complex anions. The via S or N coordinated thiocyanate groups are bonded with Ir? S? C angles of 105.7–109.7° and the Ir? N? C angle of 171.4°. The torsion angles Cl? Ir? S? C and N? Ir? S? C are 3.6–53.0°. The IR and Raman spectra of ( 1 ) are assigned by normal coordinate analysis using the molecular parameters of the X-ray determination. The valence force constants are f_d(IrS) = 1.52 and f_d(IrCl) = 1.72 mdyn/Å.     

Die Kristallstrukturen von [Ph3PMe]Cl·CH2Cl2, [Ph4P]NO3·CH2Cl2 und [Ph4P]2[SiF6]·CH2Cl2

Crystal Structures of [Ph₃PMe]Cl·CH₂Cl₂, [Ph₄P]NO₃·CH₂Cl₂, and [Ph₄P]₂[SiF₆]·CH₂Cl₂ The crystal structures of the title compounds are determined by X‐ray diffraction. In all cases, the included dichloromethane molecules as well as the phosphonium cations are involved to form hydrogen bridges with the anions. [Ph₃PMe]Cl·CH₂Cl₂ ( 1 ): Space group , Z = 2, lattice dimensions at 100 K: a = 890.3(1), b = 988.0(1), c = 1162.5(1) pm, α = 106.57(1)°, β = 91.79(1)°, γ = 92.60(1)°, R₁ = 0.0253. [Ph₄P]NO₃·CH₂Cl₂ ( 2 ): Space group P2₁/n, Z = 4, lattice dimensions at 193 K: a = 1057.0(1), b = 1666.0(1), c = 1358.9(1) pm, β = 100.10(1)°, R₁ = 0.0359. [Ph₄P]₂[SiF₆]·CH₂Cl₂ ( 3 ): Space group , Z = 2, lattice dimensions at 193 K: a = 1063.9(1), b = 1233.1(1), c = 1782.5(2) pm, α = 76.88(1)°, β = 83.46(1)°, γ = 72.29(1)°, R₁ = 0.0332.     

Die molekulare und kristalline Struktur von 9,10-Dihydro-4-(3-dimethylamino-propyliden)-4H-benzo[4,5] cyclohepta[1,2-b]thiophen-hydrochlorid. Untersuchungen über synthetishe Arzneimittel, 19. Mitteilung [1]

The α-isomer of 9,10-dihydro-4-(3-dimethylamino-propylidene)-4 H-benzo[4,5] cyclohepta [1, 2-b] thiophen is shown to have the trans configuration by means of an X-ray analysis of its hydrochloride.     

Asymmetric Synthesis of Diazepino-β-lactams by [2 + 2] Cycloaddition of an ‘Evans-Sjogven’ Ketene with 1H-1,2-Diazepines

The ketene derivative of the chiral oxazolidinone 1 underwent non-concerted stereo specific [2 + 2] cycloadditions with the (Z)-imine moiety of diazepines 2 , leading thereby with good diastereoselection to the trans-β-lactam adducts 3 (major) and 4 (minor). The absolute configuration of the major cycloadduct 3a was determined by an X-ray analysis. Its formation is discussed in terms of minimisation of steric interaction in the two transition states which give sequencially the zwitterionic intermediates and the final cycloadducts.     

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.     

Diterpenoide Drüsenfarbstoffe aus Labiaten: 3β-Acetoxyfuerstion,Nilgherron A und Nilgherron B,neue Chinomethane aus Plectranthus nilgherricus BENTH.; absolute Konfiguration von Fuerstion

Leaf-gland Pigments: 3β-Acetoxyfuerstione, Nilgherron A and Nilgherron B, New Quinomethanes from Plectranthus nilgherricus BENTH . (Labiatae); Absolute Configuration of Fuerstione We have isolated from leaf-glands of the above mentioned plant the following deeply coloured quino-methane derivatives: (1) traces of the already known fuerstione ( 1a ); 11,15-dihydroxy-5,7,9 (11), 13-abietatetraen-12-one; (2) the new 3β-acetoxy-fuerstione ( 1b ); (3) nilgherron A ( 5a , I or II), a new dimeric diterpenoid quinomethane, C₄₀H₅₂O₇, formed in the plant obviously by cycloaddition of the o-quinone 8 (9aS, 11R)-11 -hydroxy-2-(1-hydroxy-1-methylethyl-9,9-dimethyl-3,4,7,8,9,9a,10,11- octahydro-5H-dibenzo [a, d]cycloheptene-3,4-dione) with fuerstione; (4) nilgherron B ( 5b , I or II), C₄₂H₅₄O₉, likewise a new compound, formed by the same type of cycloaddition (heterodiene synthesis) of 8 with 3β-acetoxyfuerstione. On the basis of ¹H-NMR. shift arguments structure I is slightly preferred to II for 5a and 5b . Model experiments have shown the easy formation of the dihydrodioxin ring by reaction of an o-benzoquinone with p-quinomethanes. The absolute configuration of fuerstione and 3β-acetoxyfuerstione has been determined by chiroptical methods.     

Stoffwechselprodukte von Mikroorganismen. 237. Mitteilung. (2S, 3R, 4R, 6R)-2,3,4-Trihydroxy-6-methylcyclohexanon aus zwei Actinomyceten-Stämmen

(2S, 3R, 4R, 6R)-2,3,4-Trihydroxy-6-methylcyclohexanone from Two Strains of Actinomycetes A tetrazolium-blue positive compound was isolated from two strains of acinomycetes. Its constitution and relative configuration 1 were determined by spectroscopic methods, and the absolute configuration by degradation to (+)-(R)-methylsuccinic acid.     

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 ).     

Synthese optisch aktiver 2-Methyl- und 2-Äthyl-1, 6-dioxaspiro [4.4]-nonan- und -[4.5]decan-Pheromone aus einem gemeinsamen chiralen Vorläufer

Synthesis of Optically Active 2-Methyl- and 2-Ethyl-1, 6-dioxaspiro [4.4]nonane- and -[4.5]decane Pheromones from a Common Chiral Precursor The versatility of the bromoepoxide 6 as chiral building block, which is readily available in both enantiomeric forms from malic acid, and which has previously been used for a vermiculine synthesis, is further demonstrated by the preparation of the title compounds 1, 3, 4 and 5 . Alkylation of 1,3-dithiane, first with the 1-ethoxyethyl-protected ω-chloroalcohols 8b or 9b and then with the (S)-(?)-bromoepoxide 6 , followed by oxirane opening with Selectride or methyl Gilman-reagent creates the desired carbon skeletons and functionality patterns 14–17 , in overall yields of 60–80%. Acetal and thioacetal hydrolyses directly furnish the spiroacetal target structures 1 and 3–5 as 3:2-diastereomeric mixtures; the E/Z-epimers 3 are separated by preparative GC. (Fig.).     

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.     

Tetrahydrofurane und Lactone,I. Synthese und Reaktionen chiraler 2,5-überbrückter Tetrahydrofurane – ein neuer Weg zu optisch aktiven γ-Lactonen und γ-Bislactonen

Tetrahydrofurans and Lactones, I. - Synthesis and Reactions of Chiral 2,5-Bridged Tetrahydrofurans - A New Approach to Optically Active γ-Lactones and γ-Bislactones Diels-Alder reaction of 3,4-hexamethylenefuran with acrylic acid gives the carboxylic acid 1a with high endo selectivity. 1a was separated into the enantiomers via the α-phenylethylammonium salts. Comparison of the CD spectra of (−)- 1a and (−)- 3 and the X-ray structural analysis of the camphanoyl derivative (−)- 4b lead to the 1R,2S,4S configuration of (−)- 1a as well. The 2,5-bridged tetrahydrofuran (−)- 5 with all-cis and RSS configuration is obtained by ozonolysis of the ester (−)- 1b . (−)- 5 can be oxidized to the γ-lactone (2R,3S)-(−)- 6 with sodium metaperiodate/potassium permanganate in 22% yield. Hydride reduction of (−)- 6 under various conditions leads to the γ-bislactones (−)- 8 and (−)- 9 or to the bislactol (−)- 10 . (−)- 8 has the same absolute configuration as the naturally occuring (−)-canadensolide.