Die diasteromeren Aurochrome: Synthese,Analytik und Chiroptische Eigenschaften

The Diastereomeric Aurochromes: Their Synthesis, Analysis and Chiroptical Properties (all-E)-Aurochrome (5,8:5′,8′-diepoxy-5,8,5′,8′-tetrahydro-β,β-carotene; 1 ) has two pairs of constitutionally identical chiral centres and, therefore, is expected to exist in four pairs of enantiomers and two meso-forms. Using starting materials with well-defined configuration, we performed the syntheses of the following pure aurochromes: (5R,8R,5′R,8′R)-aurochrome ( 2 ) and its racemate, Meso-(5R,8R,5′S,8′S)-aurochrome ( 3 ), (5 R,8 S,5′ R,8′ S)-aurochrome ( 4 ) and its racemate, meso-(5R,8S,5′S,8′R)-aurochrome ( 5 ), (5R,8R,5′R,8′S)-aurochrome ( 6 ) and its racemate. The (5RS,8RS,5′SR,8′RS)-aurochrome ( 7 ) was detected chromatographically, using a HPLC system that allows clean separation of the four racemic- (or optically active) and the two meso-aurochromes. The optically active autochromes 2 and 4 exhibit non-conservative CD spectra with strong Cotton effects of opposite but not mirror-like tracings. Solutions of aurochromes in CHCl₃, in the presence of HCl, undergo epimerization at C(8). Those epimers with CH₃ trans to C(9) slightly predominate under equilibrium conditions. Deprotonation of the phosphonate (±)- 14 with strong base causes isomerization at the terminal oxirane into a dihydrofuran. This reaction allowed convenient syntheses of the diastereoisomeric aurochromes (±)- 2, 3 , (±)- 4, 5 , (±)- 6 , and (±)- 7 and of (5RS, 8RS)- and (5RS, 8SR)-12′-apo-aurochrome-12′-als ( 21 and 22 , respectively).     

(6′RS,8′RS,2E)- und (6′RS,8′SR,2E)-3-Methyl-3-(2y,2′,6′-trimethyl-7′-oxabicyclo[4.3.0]non-9′-en-8′-yl)-2-propenal ([(5RS,8RS)- und (5RS,8SR)-5,8-Epoxy-5,8-dihydro-ionyloinden]acetaldehyd): Synthese und Röntgenstrukturanalyse

Synthesis and X-Ray Structure of (6′RS,8′RS,2E)- and (6′RS,8′SR,2E)-3-Methyl-3-(2′,2′,6′-trimethyl-7′-oxabicyclo[4.3.0]non-9′-en-8′-yl)-2-propenal ([(5RS,8RS)- and (5RS,8SR)-5,8-Epoxy-5,8-dihydro-ionylidene]acetaldehyde) To check our previous spectroscopic assignments of the structures of trans- and cis-substituted furanoid end groups of carotenoid-5,8-epoxides, we now have synthesized the title compounds. An X-ray structure determination of a single crystal of the trans-isomer (±)- -10A is in agreement with the ¹ H-NMR spectroscopic arguments: isomers with Δδ (H? C(7), H? C(8)) = 0.15–0.22 ppm and J > 1.4 for H? C(7) belong to the cis-series; Δδ in trans-compounds is < 0.07 ppm, and H? C(7) appears as a broad singulett.     

One‐Pot,Asymmetric and Diastereoselective Four‐Component Synthesis of Polyfunctional (Z)‐Alkenyl Methyl Sulfones with Three Stereogenic Centers

The reaction of 1‐(trimethylsilyloxy)cyclopentene ( 9 ) with (±)‐1,3,5‐triisopropyl‐2‐(1‐(RS)‐{[(1E)‐2‐methylpenta‐1,3‐dienyl]oxy}ethyl)benzene ((±)‐ 4a ) in SO₂/CH₂Cl₂ containing (CF₃SO₂)₂NH, followed by treatment with Bu₄NF and MeI gave a 3.0 : 1 mixture of (±)‐(2RS)‐2{(1RS,2Z,4SR)‐2‐methyl‐4‐(methylsulfonyl)‐1‐[(RS)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐en‐1‐yl}cyclopentanone ((±)‐ 10 ) and (±)‐(2RS)‐2‐{(1RS,2Z)‐2‐methyl‐4‐[(SR)‐methylsulfonyl]‐1‐[(SR)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐en‐1‐yl}cyclopentanone ((±)‐ 11 ). Similarly, enantiomerically pure dienyl ether (−)‐(1S)‐ 4a reacted with 1‐(trimethylsilyloxy)cyclohexene ( 12 ) to give a 14.1 : 1 mixture of (−)‐(2S)‐2‐{(1S,2Z,4R)‐2‐methyl‐4‐(methylsulfonyl)‐1‐[(S)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐enyl}cyclohexanone ((−)‐ 13a ) and its diastereoisomer 14a with (1S,2R,4R) or (1R,2S,4S) configuration. Structures of (±)‐ 10 , (±)‐ 11 , and (−)‐ 13a were established by single‐crystal X‐ray crystallography. Poor diastereoselectivities were observed with the (E,E)‐2‐methylpenta‐1,3‐diene‐1‐ylethers (+)‐ 4b and (−)‐ 4c bearing ( 1 S )‐1‐phenylethyl and (1S)‐1‐(pentafluorophenyl)ethyl groups instead of the Greene's auxiliary ((1S)‐(2,4,6‐triisopropylphenyl)ethyl group). The results demonstrate that high α/β‐syn and asymmetric induction (due to the chiral auxiliary) can be obtained in the four‐component syntheses of the β‐alkoxy ketones. The method generates enantiomerically pure polyfunctional methyl sulfones bearing three chiral centers on C‐atoms and one (Z)‐alkene moiety.     

The Diels-Alder Reactivity of 2,2′-Ethylidenebis[3,5-dimethylfuran] and Exploratory Chemistry of the Mono-adducts

In the presence of Me₃Al, 1-cyanovinyl acetate added to 2,2′-ethylidenebis[3,5-dimethylfuran] ( 1 ) to give a 20:10:1:1 mixture of mono-adducts 4,5,6 , and 7 resulting from the same regiocontrol (‘para’ orienting effect of the 5-methyl substituent in 1 ). The additions of a second equiv. of dienophile to 4–7 were very slow reactions. The major mono-adducts 4 (solid) and 5 (liquid) have 2-exo-carbonitrile groups. The molecular structure of 4 (1RS,1′RS,2SR,4SR)-2-exo-cyano-4-[1-(3,5-dimethylfuran-2-yl)ethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate) was determined by X-ray single-crystal radiocrystallography. Mono-adducts 4 and 5 were saponified into the corresponding 7-oxanorbornenones 8 and 9 which were converted with high stereoselectivity into (1RS,1′SR,4RS,5RS,6RS)-4-[1-(3,5-dimethyl furan-2-yl)ethyl]-6-exo-methoxy-1,5-endo-dimethyl-7-oxabicyclo [2.2.1]heptan-2-one dimethyl acetal ( 12 ) and its (1′RS-stereoisomer 12a , respectively. Acetal hydrolysis of 12a followed by treatment with (t-Bu)Me₂SiOSO₂CF₃ led to silylation and pinacol rearrangement with the formation of (1RS,1′RS,5RS,6RS)-4-[(tert-butyl)dimethy lsilyloxy]-1-(3,5-dimethylfuran-2-yl)ethyl]-5-methoxy-6-methyl-3-methylidene- 2-oxabicyclo[2.2.1]heptane ( 16 ). In the presence of Me₃Al, dimethyl acetylenedicarboxylate added to 12 giving a major adduct 19 which was hydroborated and oxidized into (1RS,1′RS,2″RS,3″RS,4SR,4″RS,5 SR,6SR)-dimethyl 5-exo-hydroxy-4,6-endo-dimethyl-1-[1-(3-exo,5,5-trimeth oxy-2-endo,4-dimethyl-7-oxabicyclo[2.2.1]hept-2-yl)ethyl]-7-oxabicyclo [2.2.1]hept-2-ene-2,3-dicarboxylate ( 20 ). Acetylation of alcohol 20 followed by C?C bond cleavage afforded (1′RS,1″SR,2RS,2′″SR,3RS, 3″SR,4RS,4″SR,5RS)-dimethyl {3-acetoxy-2,3,4,5-tetrahydro-2,4-dimethyl-5-[1-(3-exo,5,5-trimethoxy ?2-endo,4-dimethyl-7-oxabicyclo[2.2.1]hept-1-yl)-ethyl]furan-2,5-diyl} bis[glyoxylate] ( 24 ).     

Synthese von enantiomerenreinen Violaxanthinen und verwandten Verbindungen

Syntheses of Enantiomerically Pure Violaxanthins and Related Compounds The epoxides 16 and ent- 16 , prepared by Sharpless-Katsuki oxidation of 15 in excellent yield and very high enantiomeric purity, were used as synthons for the preparation of (+)-(S)-didehydrovomifoliol (45) , (+)-(6S, 7E, 9E)-abscisic ester 46 , (+)-(6S, 7E, 9Z)-abscsic ester 47 , (?)-(3S, 7E, 9E)-xanthoxin (49) , (?)-(3R, 7E, 9E)-xanthoxin (50) , (3S, 5R, 6S, 3′S,5′R, 6′S, all-E)-violaxanthin (1) (3R, 5R,6S,3′R,5′R,6′S, all-E)-violaxanthin (55) and their (9Z) (see 53 , 57 ), (13Z) (see 54 , 58 ), and (15Z) (see 60 ) isomers. The novel violadione ( 61 ) was prepared from 1 by oxidation with DMSO/Ac₂O. By base treatment, 61 was converted into violadienedione (62) , a potential precursor of carotenoids with phenolic end groups.     

Stereoselective Double Friedel-Crafts Acylation of trans-μ-(2,3,6,7-Tetramethylidenebicyclo[3.2.1]octane)bis(tricarbonyliron). Crystal Structure of trans-μ-{(1RS,2RS,3SR,5RS,6SR,7SR)-C,2,3,C-η:C,6,7,C-η-[(Z,Z)-1,1′-(3,7-Dimethylidenebicyclo[3.2.1]octane-2,6-diylidene)di(2-propanone)]}bis(tricarbonyliron)

The Friedel-Crafts mono and double acylations of trans-μ-[(1RS,2RS,3SR,5RS,6SR,7SR)-C,2,3,C-η:C,6,7,C-η-(2,3,6,7-tetramethylidenebicyclo[3.2.1]octane)]bis(tricarbonyliron) ( 4 ) are highly stereoselective and yield trans-μ-{(1RS,2RS,3SR,5RS,6SR,7RS)-C,2,3,C-η :C,6,7,C-η-[(Z)-1-(3,6,7-trimethylidenebicyclo[3.2.1]-oct-2-ylidene)-2-propanone]}bis(tricarbonyliron) ( 5 ) and trans-μ-{(1RS,2RS,3SR,5RS,6SR,7SR)-C,2,3,C-η :C,6,7,C-η-[(Z,Z)-1,1′-(3,7-dimethylidenebicyclo [3.2.1] octane-2,6-diylidene)di(2-propanone)]}bis(tricarbonyliron) ( 6 ) whose structure has been established by single-crystal X-ray diffraction.     

A New Approach to the Synthesis of Long-Chain Polypropionates Based on the Diels-Alder Monoadditions of 2,2′-Ethylidenebis[3,5-dimethylfuran]

Acidic condensation of 2,4-dimethylfuran with acetaldehyde provided 2,2′-ethylidenebis[3,5-dimethylfuran] ( 7 ) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8 . Regio- and stereoselective hydroboration of the latter 7-oxanorbornadiene derivative followed by alcohol protection and methanolysis of its β-bromoacrylate moiety gave (1RS,2RS,4RS,5SR,6SR,1′RS)-methyl 4-[1′-(3″,5″-dimethylfuran-2″-yl)ethyl]-3,3-dimethoxy-6-exo-[(2-methoxy)ethoxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptane-2-endo-carboxylate ( 24 ) (Schemes 2 and 3). Reduction of 24 with LiAlH₄, followed by H₂O and MeOH elimination gave the 3-methyl-idene-7-oxanorbornan-2-one derivative 26 which underwent 7-oxa ring opening through a S_N2′ type of reaction with Me₂CuLi (Scheme 4). Stereoselective hydrogenation and ketone reduction provided (1RS, 2SR,3RS,4RS,5RS,6RS,1′SR)-1- [1″-(3 ″,5″-dimethylfuran-2″-yl)]-c-3-ethyl-c-5-[(2-methoxyethoxy)m e-c-ethyl-c-c-5-(2-methoxyethoxy)methoxy]-t-4,t-6-dimethyl-cyclohexane-r-1,c-2-diol ( 32 ), the oxidative cleavage of which with Pb(OAc)₄ generated a 6-oxo-aldehyde 33 (Schemes 4 and 5). Chemoselective protection of 33 and chemo- and stereoselective reductions generated (2RS,3RS,4SR,5SR,6SR,7RS)-7-(3′,5″-dimethylfuran-2′-yl)-2-ethyl-6-hydroxy-4-[(2-methoxyethoxy)methoxy]-3,5-dimethyloct-1-yl pivaloate ( 36 ) and its 4-hydroxy 6-epimer 40 (12 and 13 steps, resp., from adduct 8 ; Scheme 5). Oxidation of the furan ring of 36 led to a (2RS,3SR,4RS,5SR,6RS,7RS)-7-ethyl-3,5,8-trihydroxy-2,4,6-trimethyl-octanoic acid derivative 44 , a polypropionate fragment with six contiguous stereogenic centres (Scheme 6).     

Acid-Promoted Rearrangements of N-Substituted 8-Oxa-3-azatricyclo[3.2.1.02′4] octane-6,7-dicarboxylates: Remote Substituent Effects on the Regioselectivity of the N-Acylaziridine/Dihydrooxazone Rearrangement

Preparations of dimethyl (1RS,2SR,4RS,5SR,6SR,7RS)- and dimethyl (1 RS,2SR,4RS,5SR,6RS,7SR)-8-oxa-3-azatricyclo[3;2.1.0²⁴] octane-6,7-dicarboxylate 15 and 18 , resp.) and of their N-(tert-butyloxy)carbonyl ( 14 , 17 ) and V-benzoyl ( 16 , 19 ) derivatives are described. While treatment with nucleophilic acids (HCl, HBr. A^cOH) of the exo, exo-diesters 14 and 16 gave the corresponding products 23–27 of aziridine trans -addition, the exo, endo -diesters 17 and 19 led to the corresponding amino-lactones 63 (methyl (1RS,2RS,3SR,6RS,7SR,9RS)-2-{[(tert-butyloxy)carbonyl] amino}-5-oxo-4,8-dioxatricyclo[4.2.1.0 ³⁷] nonane-9-carboxylate) and 64 (methyl (1RS,2RS,3SR,6RS,7SR,9SR)-2-(benzoylamino)-5-oxo-4,8-dioxatricyclo[4.2.1.0 ^3′7] (nonane-9-carboxylate). Under non-nucleophilic acidic conditions, the N-benzoylaziridine 16 was rearranged quantitatively into dimethyl (1RS,2SR,26SR,67SR,7SR,8SR,9SR)-4-phenyl-5,10-dioxa-3-azatricyclo[4.3.1.0^2′7] dec-3-ene-8,9-dicarboxylate( 31 ), and 19 into dimethyl (1RS,2SR,26SR,67SR,7SR,8SR,9SR)-4-phenyl-3,10-dioxa-5-azatricyclo [5.2.1.0^2′6] dec-4-ene-8,9-di-carboxylate ( 65 ). Possible mechanisms of these highly selective reactions and rearrangements are discussed.     

Totalsynthese von natürlichem α-Tocopherol. 1. Mitteilung. Herstellung bifunktioneller,optisch aktiver Synthesebausteine für die Seitenkette mit Hilfe mikrobiologischer Umwandlungen

Total Synthesis of Natural α-Tocopherol. I. Preparation of Bifunctional Optically Active Precursors for the Synthesis of the Side Chain by Means of Microbiological Transformations Our concept for a new total synthesis of natural α-tocopherol includes the synthesis of a corresponding (3 R, 7 R)-configurated C₁₅ side chain to be built up by using twice an optically active C₅ unit together with an achiral C₅ end part. (S)-3-methyl-γ-butyrolactone ( 11 ) and (S)-2-methyl-γ-butyrolactone ( 9 ) represent suitable bifunctional C₅-precursors for this purpose. These two key compounds have been prepared by fermentative transformation including the enantioselective hydrogenation of the double bond of ethyl-4, 4-dimethoxy-3-methylcrotonate ( 5 ) by bakers yeast (yielding 11 after ester hydrolysis and cyclization of the fermentation product) and (E)-3-(1′, 3′-dioxolan-2′-yl)-2-buten-1-ol ( 8 ) by the fungus Geotrichum candidum (yielding directly 9 ).     

Studies for a Diastereoselective Synthesis of the Tetracyclic Diterpenic Diol Stemarin: A Model Study for a New Preparation of the Key Intermediate and the Synthesis of (+)-18-Deoxystemarin

Methods for a stereoselective preparation of compounds of type 2b , a key intermediate of a previous synthesis of the tetracyclic diterpene stemarin ( la ), have been tested on model compounds 5a, 5c , and 8a . Thus, (±)-(1RS,6SR,8SR,11SR)-hydroxytricyclo[6.2.2.0^l,6]dodecan-9-one ( 5a ) was transformed by the Mitsunobu reaction into (±)-(1RS,6SR,8SR,11RS)-11-(benzoyloxy)tricyclot[6.2.2.0^1,6]dodecan-9-one ( 6b ; Scheme 2). The latter was also obtained from (±)-(1RS,6SR,8SR,11RS)-11-[(4)-toluenesulfonyloxy]tricyclo[6.2.2.0^1,6]dodecan-9-one ( 5c ) by the action of Et₄N (PhCOO) in acetone. Compound 6b was then converted into (±)-(1RS,6RS,8RS,9RS)-tricyclo[6.2.2.0^1,6]dodecan-9-ol ( 8b ), a model for 2b . Compound 8b was also prepared from its epimer 8a by the Mitsunobu reaction via ester 7b . The inversion of configuration of bicyclo[2.2.2]octan-2-ols or derivates was not previously described. The model studies paved the way to the diastereoselective synthesis of (+)-18-deoxystemarin ( 1b ) via 12β-hydroxy-13-methyl-9β,13β-ethano-9β-podocarpan-15-one ( 10a ) and 13-methyl-9β,13β-ethano-9β-podpcarpan-12α-ol ( 11b ).     

Total Asymmetric Synthesis of Doubly Branched Carba-hexopyranoses and Amino Derivatives Starting from the Diels-Alder Adducts of Maleic Anhydride to Furfuryl Esters

The Diels-Alder adducts of maleic anhydride to furfuryl esters were reduced into 7-oxabicyclo[2.2.1]hept-5-ene-1,2-exo,3-exo-trimethanol (±)- 15 and enantiomerically pure (−)- 15 (Scheme 1). The tripivalate of (±)- 15 was converted into (1RS,2RS,3RS,4RS,5SR,6SR)-1,5,6-tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol ((±)- 23 ; Scheme 2). Reaction of BBr₃ with the triacetate (±)- 30 of (±)- 15 gave (1RS,2RS,5RS,6RS)-5-bromo-6-hydroxycyclohex-3-ene-1,2,3-trimethyl triacetate ((±)- 31 ) at −78°, and (1RS,2RS,5SR,8SR)-2-endo-hydroxy-6-oxabicylo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)- 32 ) at 0° (Scheme 3). Single-crystal X-ray diffraction of (1RS,2RS,5SR,8SR)-2-acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)- 33 ) was carried out. Displacement of bromide (+)- 31 (derived from (−)- 15 ) with azide anion gave (+)- 38 which was transformed into (+)-(1R,2R,5S,6S)-5-amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((+)- 40 ) (Scheme 4). Reaction of (±)- 31 with BBr₃ at 0°, followed by azide disubstitution led to (1RS,2RS,5SR,6SR)-5-amino-3-(aminomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethanol ((±)- 45 ). Dihydroxylation of (±)- 38 and further transformations gave (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((±)- 49 ) and (1RS,2RS,3SR,4RS,5SR,6RS)-2,3-dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethanol ((±)- 55 ) (Schemes 5 and 6). Expoxidation of the 4-nitrobenzoate (±)- 61 of (±)- 38 allowed the preparation of (1RS,2RS,3SR,4RS,5RS)-5-amino-1,4-dihydroxycyclohexane-1,2,3-trimethanol ((±)- 65 ) and of (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-4-hydroxy-7-oxabicyclo[4.1.0]heptane-1,2,3-trimethanol ((±)- 67 ) (Scheme 7). The new unprotected polyols and aminopolyols were tested for their inhibitory activity toward commercially available glycohydrolases. At 1 mM concentration, 34, 30, and 31% inhibition of β-galactosidase from bovine liver was observed for (+)- 40 , (±)- 65 , and (±)- 67 , respectively.     

Synthese von enantiomerenreinem Mimulaxanthin und seiner (9Z,9′Z)- und (15Z)-Isomeren

Synthesis of Enantiomerically Pure Mimulaxanthin and of Its (9Z,9′Z)- and (15Z)Isomers We present the details of a synthesis of optically active, enantiomerically pure stereoisomers of mimulaxanthin (=(3s,5R,6R,3′S,5′R,6′R)-6,7,6′,7′-tetradehydro-5,6,5′,6′-tetrahydro-β,β-carotin-3,5,3′,5′-tetrol) either as free alcohols 1a and 24a or as their crystalline (t-Bu)Me₂Si ethers 1b and 24b . Grasshopper ketone 2a , a presumed synthon, unexpectedly showed a very sluggish reaction with Wittig-Horner reagents. Upon heating with the ylide of ester phosphonates, an addition across the allenic bond occurred. On the contrary, a slow but normal 1,2-addition took place with the ylide from (cyanomethyl)phosphonate but, unexpectedly, with concomitant inversion at the chiral axis. So a mixture of(6R,6S,9E,9Z)-isomers 6 – 9 was produced {(Scheme 1). However, a fast and very clean 1,2-addition occurred with the ethynyl ketone 12 to yield the esters 13 and 14 (Scheme 2). DIBAH reduction of the separated stereoisomers gave the allenic alcohols 15 and 16 in high yield. Mild oxidation to the aldehydes 17 and 18 followed by their condensation with the acetylenic C₁₀-bis-ylide 19 led to the stereoisomeric 15,15′-didehydromimulaxanthins 20 and 22 , respectively (Schemes 3 and 4). Mimulaxanthins 1 and 24 were prepared by partial hydrogenation of 20 and 22 followed by a thermal (Z/E)-isomerization. As expected, the mimulaxanthins exhibit very weak CD curves, obviously caused by the allenic bond that insulates the chiral centers in the end group from the chromophor. On the contrary, some of the C₁₅-allenic synthons showed not only fairly strong CD effects but also a split CD curve which, in our interpretation, results from an exciton coupling between the allene and the C(9)?C(10) bond. We postulate a rotation around the C(8)? C(9) bond, presumably caused by an intramolecular H-bond in 16 or by a dipol interaction between the polarized double bonds in 6 , 7 , 8 , and 17 .     

(all-E)-12′-Apozeaxanthinol,Persicaxanthine und Persicachrome

( all-E)-12′-Apozeanthinol, Persicaxanthine, and Persicachromes Reexamination of the so-called ‘persicaxanthins’ and ‘persicachromes’, the fluorescent and polar C₂₅-apocarotenols from the flesh of cling peaches, led to the identification of the following components: (3R)-12′-apo-β-carotene-3,12′-diol ( 3 ), (3S,5R,8R, all-E)- and (3S,5R,8S,all-E)-5,8-epoxy-5,8-dihydro-12′-apo-β-carotene-3,12′-diols (4 and 5, resp.), (3S,5R,6S,all-E)-5,6-epoxy-5,6-dihydro-l2′-apo-β-carotene-3,12′-diol =persicaxanthin; ( 6 ), (3S,5R,6S,9Z,13′Z)-5,6-dihydro-12′apo-β-carotene-3,12′-diol ( 7 ; probable structure), (3S,5R,6S,15Z)-5,6-epoxy-5,6-dihydro-12′-apo-β-carotene-3,12′-diol ( 8 ), and (3S,5R,6S,13Z)-5,6-epoxy-5,6-dihydro-12′-apo-β-carotene-3,12′-diol ( 9 ). The (Z)-isomers 7 – 9 are very labile and, after HPLC separation, isomerized predominantly to the (all-E)-isomer 6 .     

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. IV. Neues Konzept für die Synthese von (3RS, 3′RS)-, (3S, 3′S)- und (3R, 3′R)-9,9′-dicis-7,8,7′,8′-Tetradehydroastaxanthin

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone. IV. A Novel Concept for the Synthesis of (3RS, 3′RS)-, (3S, 3′S)- and (3R, 3′R)-9,9′-dicis-7,8,7′,8′-Tetradehydroastaxanthin Starting from readily available intermediates of the synthesis of astaxanthin, (3RS, 3′RS)-, (3R, 3′R)- and (3S, 3′S)-9,9′-di-cis-tetradehydroastaxanthin ( 1, 1a and 1b , resp.) were synthesized, 1 and 1b for the first time. Key features of this concept are: a) use of the unprotected, acetylenic phosphonium salts 8–12 , b) a two-step synthesis with 47% overall yield, and c) good chemical and optical purity of the end products.     

Stereoselective Double Functionalization of Iron-Carbonyl Complexes of 5,6,7,8-Tetramethylidenebicyclo[2.2.2]oct-2-ene. Crystal Structure and Absolute Configuration of (–)-trans-μ-[(2S,5R,7S)-C,5,6,C-η:C,7,8,C-η-(6,7,8-trimethylidene-5-((Z)-2-oxopropylidene)-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron)

The Friedel-Crafts monoacylation of trans-η-[(1RS,2RS,4SR,5SR,6RS,7SR,8SR)-C,5,6,C-η:C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron) ((±)- 5 ) is highly stereoselective and yields trans-η-[(1RS,2RS,4RS,5SR,6RS,7RS,8SR)-C,6-η,oxo-σ:C,7,8,C-η-(6,7,8-trimethylidene-5-((Z)-2-oxopropylidene)-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron) ((±)- 8 ) which equilibrates with the trans-η-[(1RS,2RS,4RS,5SR,6RS,7RS,8SR)-C,5,6,C-η:C,7,8,C-η-(6,7,8-trimethylidene-5-((Z)-2-oxopropylidene)-2-bicyclo[2.2.2]octyl acetate)]-bis(tricarbonyliron) ((±)- 9 ) on heating. Optically pure (–)- 9 has been prepared from the corresponding optically pure alcohol (+)- 4 . The structure and absolute configuration of (–)- 9 was established by single-crystal X-ray diffraction.     

Regio‐ and stereospecific assembly of dispiro[indoline‐3,3′‐pyrrolizine‐1′,5′′‐thiazolidines] from simple precursors using a one‐pot procedure: synthesis,spectroscopic and structural characterization,and a proposed mechanism of formation

The synthesis and characterization of three new dispiro[indoline‐3,3′‐pyrrolizine‐1′,5′′‐thiazolidine] compounds are reported, together with the crystal structures of two of them. (3RS,1′SR,2′SR,7a′SR)‐2′‐(4‐Chlorophenyl)‐1‐hexyl‐2′′‐sulfanylidene‐5′,6′,7′,7a′‐tetrahydro‐2′H‐dispiro[indoline‐3,3′‐pyrrolizine‐1′,5′′‐thiazolidine]‐2,4′′‐dione, C₂₈H₃₀ClN₃O₂S₂, (I), (3RS,1′SR,2′SR,7a′SR)‐2′‐(4‐chlorophenyl)‐1‐benzyl‐5‐methyl‐2′′‐sulfanylidene‐5′,6′,7′,7a′‐tetrahydro‐2′H‐dispiro[indoline‐3,3′‐pyrrolizine‐1′,5′′‐thiazolidine]‐2,4′′‐dione, C₃₀H₂₆ClN₃O₂S₂, (II), and (3RS,1′SR,2′SR,7a′SR)‐2′‐(4‐chlorophenyl)‐5‐fluoro‐2′′‐sulfanylidene‐5′,6′,7′,7a′‐tetrahydro‐2′H‐dispiro[indoline‐3,3′‐pyrrolizine‐1′,5′′‐thiazolidine]‐2,4′′‐dione, C₂₂H₁₇ClFN₃O₂S₂, (III), were each isolated as a single regioisomer using a one‐pot reaction involving l ‐proline, a substituted isatin and (Z)‐5‐(4‐chlorobenzylidene)‐2‐sulfanylidenethiazolidin‐4‐one [5‐(4‐chlorobenzylidene)rhodanine]. The compositions of (I)–(III) were established by elemental analysis, complemented by high‐resolution mass spectrometry in the case of (I); their constitutions, including the definition of the regiochemistry, were established using NMR spectroscopy, and the relative configurations at the four stereogenic centres were established using single‐crystal X‐ray structure analysis. A possible reaction mechanism for the formation of (I)–(III) is proposed, based on the detailed stereochemistry. The molecules of (I) are linked into simple chains by a single N—H…N hydrogen bond, those of (II) are linked into a chain of rings by a combination of N—H…O and C—H…S=C hydrogen bonds, and those of (III) are linked into sheets by a combination of N—H…N and N—H…S=C hydrogen bonds.     

Das Carotinoidspektrum der Hagebutten von Rosa pomifera: Nachweis von (5Z)-Neurosporin; Synthese von (3R, 15Z)-Rubixanthin

Carotenoids from Hips of Rosa pomifera: Discovery of (5Z)-Neurosporene; Synthesis of (3R, 15Z)-Rubixanthin Extensive chromatographic separations of the mixture of carotenoids from ripe hips of R. pomifera have led to the identification of 43 individual compounds, namely (Scheme 2): (15 Z)-phytoene (1) , (15 Z)-phytofluene (2) , all-(E)-phytofluene (2a) , ξ-carotene (3) , two mono-(Z)-ξ-carotenes ( 3a and 3b ), (6 R)-?, ψ-carotene (4) , a mono-(Z)-?, ψ-carotene (4a) , β, ψ-carotene (5) , a mono-(Z)-β, ψ-carotene (5a) , neurosporene (6) , (5 Z)-neurosporene (6a) , a mono-(Z)-neurosporene (6b) , lycopene (7) , five (Z)-lycopenes (7a–7e) , β, β-carotene (8) , two mono-(Z)-β, β-carotenes (probably (9 Z)-β, β-carotene (8a) and (13 Z)-β, β-carotene (8b) ), β-cryptoxanthin (9) , three (Z)-β-cryptoxanthins (9a–9c) , rubixanthin (10) , (5′ Z)-rubixanthin (=gazaniaxanthin; 10a ), (9′ Z)-rubixanthin (10b) , (13′ Z)- and (13 Z)-rubixanthin (10c and 10d , resp.), (5′ Z, 13′ Z)- or (5′ Z, 13 Z)-rubixanthin (10e) , lutein (11) , zeaxanthin (12) , (13 Z)-zeaxanthin (12b) , a mono-(Z)-zeaxanthin (probably (9 Z)-zeaxanthin (12a) ), (8 R)-mutatoxanthin (13) , (8 S)-mutatoxanthin (14) , neoxanthin (15) , (8′ R)-neochrome (16) , (8′ S)-neochrome (17) , a tetrahydroxycarotenoid (18?) , a tetrahydroxy-epoxy-carotenoid (19?) , and a trihydroxycarotenoid of unknown structure. Rubixanthin (10) and (5′ Z)-rubixanthin (10a) can easily be distinguished by HPLC. separation and CD. spectra at low temperature. The synthesis of (3 R, 15 Z)-rubixanthin (29) is described. The isolation of (5 Z)-neurosporene (6a) supports the hypothesis that the ?-end group arises by enzymatic cyclization of precursors having a (5 Z)- or (5′ Z)-configuration.     

Face Selectivity of the Diels-Alder Reaction of Hexadienone Moieties Grafted onto the Bicyclo[2.2.2]octene Skeleton and Perturbed by a Remote Tricarbonylbutadieneiron Group

Selective oxidations of bis(tricarbonyliron) complexes of methyl (3,7,8-trimethylidenebicyclo[2.2.2]oct-5-en-2-ylidene)methyl ketones 15 – 17 afforded selectively the tricarbonyl {(1RS,4SR,7SR,8RS)-C,7,8,C-η-[methyl (3,7,8-trimethylidenebicyclo[2.2.2]oct-5-en-(2Z)-2-ylidene)methyl ketone]}iron ( 12 ), the corresponding (2E)-derivative 13 and the tricarbonyl{(1RS,2RS,3SR,4SR)-C,2,3,C-η-[methyl (3,7,8-trimethylidenebicyclo[2.2.2]oct-5-en-(2Z)-2-ylidene)methyl ketone]}iron ( 18 ). The stereoselectivity of the Diels-Alder reactions of the uncomplexed (Z)- and (E)-hexadienone 12 and 13 , respectively, was established. The face of the diene syn with respect to the C(5), C(6) etheno bridge was preferred for the cycloadditions of N-phenyltriazolinedione (NPTAD). In contrast, the reactions of dimethyl acetylenedicarboxylate (DMAD) and methyl propynoate showed a slight preference for addtion to the face of the hexadienones anti with respect to the etheno bridges of 12 and 13 . The crystal structure of the adduct 25 resulting from the cycloaddition of NPTAD to 12 is reported.     

Stereoselective Synthesis of 5a-Ethyl-1,2,3,3a,4,5,5a,6,9a,9b-decahydro- 1,3,4-trihydroxy-3a-(hydroxymethyl)-7H-benz[e]inden-7-one Derivatives

Homochiral Diels-Alder cyclodimerization of (±)-6-ethenyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-ol ( 1 ) followed by oxidation gives (1RS,4RS,4aSR,4bSR,5RS,8RS,8aRS)-8a-ethenyl-1,3,4,4a,4b,5,6,8,8a,9-decahydro-1,4:5,8-diepoxyphenanthrene-2,7-dione ( 18 ). Selective hydrogenation followed by epoxidation produced (1RS,4RS,4aRS,5aRS,6aRS,7RS,10RS,10aSR,10bRS)-6a-ethyl-1,4,5a,6,6a,7,9,10,10a,10b-decahydro-1,4:7,10-diepoxyphenanthro[8a,9-b]oxirene-3,8-dione ( 21 ), which was solvolyzed (Me₃SiOSO₂CF₃, Piv₂O) with concomitant pinacol rearrangement involving an acyl-group migration to give a 6-oxo-7-oxabicyclo[2.2.1]hept-2-yl cation intermediate, which finally generated (1RS,3SR,3aRS,4SR,5aRS,6RS,9RS,9aSR,9bSR)-5a-ethyl-1,4,5,5a,6,7,8,9,9a,9b-decahydro-7,10-dioxo-3H-6,9-epoxy-1,3a-ethanonaphtho[1,2-c]furan-3,4-diyl bis(2,2-dimethylpropanoate) ( 24 ). Photo-reductive 7-oxa bridge opening of 24 , followed by water elimination and silylation, provided (1RS,3SR,3aRS,4SR,5aSR,9aSR,9bSR)-7-{[(tert-butyl)dimethylsilyl]oxy}-5a-ethyl-1,4,5,5a,9a,9b-hexahydro-10-oxo-3H-1,3-ethanonaphtho[1,2-c]furan-3,4-diyl bis(2,2-dimethylpropanoate) ( 34 ). Reduction of 34 with NaBH₄ in MeOH followed by desilylation and alcohol protection produced (1RS,3RS,3aRS,4SR,5aSR,9aSR,9bSR)-5a-ethyl-2,3,3a,4,5,5a,6,7,9a,9b-decahydro-1,3-bis(methoxymethoxy)-3a-[(methoxymethoxy)methyl]-7-oxo-1H-benz[e]inden-4-yl 2,2-dimethylpropanoate ( 5 ), a polyoxy-substituted decahydro-1H-benz[e]indene derivative with cis-transoid-trans junction for the two cyclohexane and the cyclopentane rings bearing an angular 3a-(oxymethyl) substituent.     

Beitrag zur Analytik und Synthese von 3-Hydroxy-4-oxocarotinoiden

Contribution to the Analytical Separation and the Synthesis of 3-Hydroxy-4-oxocarotenoids (3RS,3′RS)-Astaxanthin (= 3,3′-dihydroxy-β,β-carotene-4,4′-dione, 1:1-mixture of racemate and meso-form; 1 ) can be separated into its optical isomers (3S,3′S)- 1a , (3R,3′R)- 1b and meso-(3R,3′S)- 1c via the corresponding diastereomeric di-(?)-camphanates. Some aspects of the configurational stability of astaxanthin are discussed. - HPLC. analysis of the (?)-camphanates of 3-hydroxy-4-oxocarotenoids provides, in suitable cases and supported by spectroscopic data, an analytical method for the simultaneous determination of constitution and chirality.