Asymmetric synthesis of (S,R)- and (R,R)-methiin stereoisomers

Abstract

An asymmetric synthesis of (+)- and (–)-methiine (S-methyl-(R)-cysteine sulfoxide) diastereomers has been developed. These natural sulfur compounds were isolated from a variety of Brassica vegetables. As the starting compound, (R)-cysteine was used, which was methylated to form (R)-S-methylcysteine. Then the oxidation of S-methylcysteine with tert-butyl hydroperoxide catalyzed by the chiral tetra(isopropylate)titanium/(S)- or (R)-Binol complex led to the formation of (1?R,2S)-(+)- or (1?R,2R)-(–)-methiin stereomers.     

Crystal structure of (S,S)-diphenylethanediammonium (R,R)-tartrate

Summary The crystal structure of (–)-diphenylethanediammonium-(R,R)-tartrate was determined. From this structure determination, the (S,S) configuration was assigned to the (–)-diphenylethanediamine. The asymmetric unit of the crystal structure contains two units of the title compound plus one molecule of ethanol and one water molecule, which form an intricate network of 19 hydrogen bonds.

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Die Kristallstruktur von (S,S)-Diphenylethandiammonium-(R,R)-tartrat

Zusammenfassung Es wurde die Kristallstruktur von (–)-Diphenylethandiammonium-(R,R)-tartrat bestimmt. Aus dieser Strukturbestimmung ergab sich die Zuordnung der (S,S)-Konfiguration zum (–)-Diphenylethandiamin. Die asymmetrische Einheit der Kristallstruktur besteht aus zwei Formeleinheiten der Titelverbindung sowie einem Molekül Ethanol und einem Wassermolekül, welche ein komplexes Netzwerk von insgesamt 19 Wasserstoffbrücken bilden.

     

Stereochemische Korrelationen zwischen (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin und (–)-(R)-Linalol

Stereochemical Correlations between (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin and (–)-(R)-Linalol The optically active C₅- and C₄-building units 1 and 2 with their hydroxy group at a asymmetric C-atom were transformed to (–)-(1S,5R)-Frontalin ( 7 ) and (–)-(3R)-Linalol ( 8 ) respectively; 1 and 2 had been used earlier in the preparation of the chroman part of (2R,4′R,8′R)-α-Tocopherol ( 6a , vitamin E), and for introduction of the side chain in (25S,26)-Dihydroxycholecalciferol ((25S)- 4 ), a natural metabolite of Vitamin D₃. The stereochemical correlations resulting from these converions fit into a coherent picture with those correlations already known from literature and they confirm our earlier stereochemical assignments. A stereochemical assignment concerning the C(25)-epimers of 25,26-Dihydroxycholecalciferol that was in contrast to our findings and that initiated the conversion of 1 and 2 to 7 resp. 8 for additional stereochemical correlations has been corrected in the meantime by the authors [26].     

Synthesis and Conformation of (5R,8R,10R)-8-(Methylthiomethyl)ergoline-6-carboxamidine

The title compound 7 and two related novel ergolines have been synthesised from (5R,8R,10R)-8-(methyl-thiomethyl)ergoline-6-carbonitrile ( 4 ). The guanidine function of 7 induces a boat conformation of ergoline-ring D, as demonstrated by a careful NMR spectroscopic analysis of 7 and its N-hydroxy congener 6 . Diphenylphosphinodithioic acid has been used to convert the cyanamide function of 4 into the thiourea function at (5R,8R,10R)-8-(methylthiomethyl)ergoline-6-thiocarboxamide ( 5 ).     

Synthesis of (5R,8S,10R)-6-(Allyloxy)- and (5R,8S,10R)-6-(Propyloxy)ergolines from the 6-Methyl Precursors

Novel (5R,8S,10R)-6-(allyloxy)- and (5R,8S,10R)-6-(propyloxy)ergolines have been synthesized by use of a Meisenheimer [2,3]-sigmatropic rearrangement of a (5R,8S,10R)-6-allyl-ergoline N⁶-oxide as key step.     

Synthesis of (all-E,2R,2′R)-oscillol

Optically active (all-E,2R,2′R)-oscillol (= (all-E,2R,2′R)-3,4,3′,4′-tetradehydro-1,2,1′,2′-tetrahydro-ψ,ψ-carotene-1,2,1′,2′-tetrol; 1 ) was synthesized according to the C₁₀ + C₂₀ + C₁₀ = C₄₀ strategy, applying the Wittig reaction to couple the synthons 4 and 6 . The chiral centre was introduced by a Sharpless dihydroxylation of 3-methylbut-2-enyl 4-nitrobenzoate ( 8 ).     

A Convenient Stereoselective Synthesis of (1R,2S,3R,4S)-3-(Neopentyloxy)isoborneol

A convenient preparation of (1R,2S,3R,4S)-3-(neopentyloxy)isoborneol (= (1R,2S,3R,4S)-3-(2,2-dimethyl-propoxy)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol; 1a ), a valuable chiral auxiliary, is described. The synthesis involves six steps starting from the readily available camphorquinone ( 5 ) and gives 1a in 48% overall yield. The key step is the chemoselective hydrolysis of the less hindered 1,3-dioxolane moiety in the camphorquinone di-acetal 4 .     

Preparation of (R)-11-hydroxyaporphine directly from (R)-10,11-dihydroxyaporphine ((R)-apomorphine)

A Regioselective synthesis of (R)-11-hydroxyaporphine 2 directly from (R)-10,11-dihydroxyaporphine ((R)-apomorphine, 1 ) is described for the first time. The isopropylidene ketal ring of 10,11-(isopropyl-idenyldioxy)aporphine 5 obtained by the isopropylidenation of apomorphine was regioselectively opened by ten equivalents of trimethylaluminum to give (R)-10-hydroxy-11-tert-butyloxyaporphine 6 . The free 10-hydioxyl position of 6 was triflated with N-pbenyltrifluoromethanesulfonimide and potassium carbonate under reflux to give (R)-10-[(trifluoromethyl)sulfonyloxy]-11-tert-butyloxyaporphine 7 . The reduced product, 11-tert-butyloxyaporphine 8 was prepared from 7 by a palladium-catalyzed hydrogenolysis. The ether cleavage of (R)-11-tert-butyloxyaporphine with 48% hydrobromic acid afforded the desired (R)-11-hydroxyaporphine 2 in good yield.     

(E,E)-1,1′-[1,2-Bis(4-chlorophenyl)ethane-1,2-diyl]bis(phenyldiazene) revisited: threefold configurational disorder of (S,S), (R,R) and (S,R) isomers,a detailed critique

Crystal structures described as concomitant triclinic ( I ) and monoclinic ( II ) polymorphs of meso-(E,E)-1,1′-[1,2-bis(4-chlorophenyl)ethane-1,2-diyl]bis(phenyldiazene) [Mohamed et al. (2016). Acta Cryst. C 72 , 57–62] have been re-investigated. The published model for II was distorted due to forcing the symmetry of space group C2/c on an incomplete structure model. It is shown here to be a likely three-component superposition of S,S and R,R enantiomers with a lesser amount of the meso form. A detailed analysis of how the improbable distortion in the published model aroused suspicion and the subsequent construction of undistorted chemically and crystallographically plausible alternatives having the symmetry of Cc and C2/c is presented. For the sake of completeness, an improved model for the triclinic P structure of the meso isomer I , revised to include a minor disorder component, is also given.     

Synthetic modifications of bifunctional homoallylamines: Synthesis of 2-arylpiperidines, (R)-anatabine and (R)-anabasine

The chiral homoallylamines with orthogonal bifunctional handle, an amine, and a pendant allyl unit are available to be easily converted into N-heterocycles. The N-allylation and Ru-catalyzed ring-closing metathesis delivered the bioactive 2-arylpiperidines, Nicotiana tabacum alkaloids (R)-anatabine and (R)-anabasine in three steps. A formal synthesis of (R)-N-methylanatabine and (R)-N-methylanabasine is also completed.     

Stereoselectivity in Reactions of Metal Complexes IV. Asymmetric Synthesis of (2R, 7S, 10R)- and (2R, 7R, 10R)-2, 10-diamino-5, 5, 7-trimethyl-4, 8-diazaundecanenickel (II) by Stereoselective Hydrogenation of (2R, 10R)-2, 10-diamino-5, 5, 7-trimethyl-4, 8-diaza-7-undecenenickel(II)

The catalytic hydrogenation of (2R, 10R)-2, 10-diamino-5, 5, 7-trimethyl-4, 8-diaza-7-undecenenickel(II) yields two products when the reaction is performed in the presence of ethylenediamine, but only one, when ethylenediamine is absent. The stereochemistry of the reaction is discussed and a proposal for the absolute configuration of the two diastereomeric complexes and the free ligands is given on the base of CD.- and NMR.-spectra.     

Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

Synthesis of (R)-1,2,11-trihydroxy-, (R)-2,11-, and (R)-2,10-dihydroxyaporphines — non naturally occurring aporphine alkaloids from pukateine and thebaine

The synthesis of (R)-2,10-dihydroxyaporphine ( 3a ), (R)-2,10-dihydroxy-N-n-propylnoraporphine ( 3b ) from thebaine and (R)-2,11-dihydroxyaporphine (7), and 1,2,11-trihydroxyaporphine ( 9 ), from pukateine is reported. The rearrangement of thebaine and northebaine with methanesulfonic acid to 1a and 1b with subsequent N-propylation gave 1b . Tetrazolyation of 1a, 1b and hydrogenolysis of 2a and 2b on Pd/C in acetic acid with subsequent O-demethylation with hydrobromic acid (48%) led to 3a and 3b . R(-)-2,11-Dihydroxyaporphine ( 7 ) was prepared by lithium/ammonia reduction of pukateine. (R)-1,2,11-Trihydroxyaporphine ( 9 ) was synthesized by reaction of pukateine with boron tribromide in dichloromethane.     

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.     

Synthesis of (3R,5S,6R) 2,6-Diacetoxymethylclavam from D-Galactal

Abstract

N- (t-Butyl)dimethylsilyl-2- C: 1 - N- car bony 1 - 2 -deoxy- α-D-galactopyran-osylamine (1) was tritylated and the product was subjected to a glycolic cleavage to give dialdehyde 10. Subsequently, compound 10 was transformed into bromide 14 using standard procedures. The fluoride anion induced cyclization in 14 afforded clavam 15.     

O,O'-Di-p-toluoyl-(2R,3R)-tartaric acid as supramolecular resolving agent

O,O'-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA) was investigated as supramolecular complex (SMC) forming resolving agent with three racemic alcohols (menthol, 4-methyl-2-pentanol, trans-2-iodo-cyclohexanol) by preparative scale experiments and thermoanalytical measurements. Despite the very small structural difference (two methyl groups) between the O,O'-dibenzoyl-(2R,3R)-tartaric acid (DBTA) and DPTTA, their SMC forming properties with water and racemic alcohols is very different. While DBTA forms SMC with all the three investigated alcohols, DPTTA forms SMC only with trans-2-iodo-cyclohexanol. DPTTA binds the guest compound less strongly and the stoichiometry of the SMC is also different. The weaker interactions resulted in less effective optical resolutions. The results of these investigations remind us, that in optical resolutions during the chiral discrimination process the weaker interactions have a determining role, since DBTA and DPTTA have the possibility to form the same strong (O-H···O and N-H···O) hydrogen bond network. This revised version was published online in August 2006 with corrections to the Cover Date.     

(+)-(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.     

Full stereochemical understanding in a new (2R,3R,4R)-4-hydroxyisoleucine synthesis

We present the crystal and molecular structures of 2,3,6,7,8,8a-hexa­hydro-6,8-methano-7,7,8a-tri­methyl-3-(1-methyl-2-oxo­propyl­idene)-5H-1,4-benzoxazin-2-one, C₁₆H₂₁NO₃, (III), and 2,3,6,7,8,8a-hexa­hydro-3-(2-hydroxy-1-methyl­propyl)-6,8-methano-7,7,8a-tri­methyl-5H-1,4-benzoxazin-2-one, C₁₆H₂₅NO₃, (V). These compounds are two of the four key intermediates in our synthetic route to (2R,3R,4R)-4-hydroxy­isoleucine. The two structures provide a full understanding of the stereochemistry in successive steps. This synthesis was based on a new optically pure chiral oxazinone auxiliary derived from (1R,2R,5R)-2-hydroxy­pinan-3-one.     

An Easy Entry to (1S, 2S) and (1R, 2R)-Threo-Ifenprodil

A facile and practical synthesis of enantiomerically pure (L) or (D)-threo-Ifenprodil was accomplished from (1S, 2S)- and (1R, 2R)-threo-1-(p-nitrophenyl)-2-amino-propan-1, 3-diol via 3-phenylthio derivatives followed by Raney nickel reduction and conversion of the aromatic amine into phenol.