Totalsynthese von natürlichem α-Tocopherol 3. Mitteilung. Aufbau der Seitenkette mit (−)-(S)-2-Methyl-γ-butyrolacton als zentralem Baustein

Total Synthesis of Natural α-Tocopherol (?)-(S)-2-Methyl-γ-butyrolactone ( 2 ) represents a versatile chiral C₅-synthon. It serves as key intermediate in one of the syntheses of certain isoprenoid derivatives such as (R)-dihydrocitronellol, (3R, 7R)-hexahydrofarnesol and vitamin E of natural configurations. Their syntheses are described in detail.     

Totalsynthese von natürlichem α-Tocopherol. 2. Mitteilung. Aufbau der Seitenkette aus (−)-(S)-3-Methyl-γ-butyrolacton

Total Synthesis of Natural α-Tocopherol A short and efficient route to optically pure (+)-(3 R, 7 R)-trimethyldodecanol ( 14 ) is demonstrated, 14 serving as side chain unit in the preparation of natural vitamin E. The synthesis of 14 is based on the concept of using a single optically active C₅-synthon of suitable configuration and functionalization to introduce both asymmetric centres in 14 . (?)-(S)-3-Methyl-γ-butyrolacton ( 1 ) and ethyl (?)-(S)-4-bromo-3-methylbutyrate ( 2 ), respectively, is used in a sequence of either two Grignard C,C-coupling reactions 5 → 8 and 12 → 13 or two Wittig reactions 17a → 18 and 20 → 21 to achieve this goal. 14 is converted to (2 R, 4′R, 8′R)-α-tocopherol (= vitamin E) by coupling with a chroman unit in known manner. Optical purity of products and intermediates is established.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. V. Synthese von (3R, 3′R)-, (3S, 3′S)- und (3R,3′S; meso)-Zeaxanthin durch asymmetrische Hydroborierung. Ein neuer Zugang zu Optisch aktiven Carotinoidbausteinen. Vorläufige Mitteilung

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. V. Synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin by Asymmetric Hydroboration. A New Approach to Optically Active Carotenoid Building Units The synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin ( 1 ), ( 19 ) and ( 21 ) is reported utilizing asymmetric hydroboration as the key reaction. Thus, safranol isopropenylmethylether ( 4 ) is hydroborated with (+)- and (?)-(IPC)₂BH to give the optically pure key intermediates 5 and 7 resp., which are transformed into the above-mentioned C₄₀-compounds.     

C45- und C50-Carotinoide. 4. Mitteilung. Synthese von optisch aktiven cyclischen C20-Bausteinen und von (2R,2′R)-2,2′-Bis(4-hydroxy-3-methyl-2-butenyl)-β,β-carotin ( = C.p. 450)

C₄₅- and C₅₀-Carotenoids: Synthesis of Optically Active Cyclic C₂₀-Building Blocks and of (2R,2′R)-2,2′-Bis(4-hydroxy-3-methyl-2-butenyl)-β,β-carotene ( = C.p. 450) The synthesis of the optically active C₂₀-building blocks (R)- 26 and (R)- 39 and of the optically active cyclic C₅₀-carotenoid C.p. 450 ( 3 ) starting from (?)-β-pinene is reported.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. IV. Synthese von (3R, 3′R, 6′R)-Lutein. Vorläufige Mitteilung

Synthesis of optically active natural carotenoids and structurally related compounds. IV. Synthesis of (3R, 3′R, 6′R)-lutein The synthesis of (3R, 3′R, 6′R)-lutein ( 19 ) according to the building principle C₂₅+C₁₅?C₄₀ is reported utilizing (R)-4-hydroxy-2,6,6-trimethyl-2-cyclohexen-1-one ( 4 ) as a readily available key intermediate.     

C45 und C50-Carotinoide. 6. Mitteilung. Synthese eines optisch aktiven cyclischen C20-Bausteins und von Decaprenoxanthin (= (2R, 6R, 2′R, 6′R)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-ϵ, ϵ-carotin)

C₄₅- and C₅₀-Carotenoids: Synthesis of an Optically Active Cyclic C₂₀-Building Block and of Decaprenoxanthin ( = (2R, 6R, 2′R, 6′R)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-?, ?-carotene) The synthesis of the optically active cyclic C₂₀-building block (R, R) -15 and of the optically active C₅₀-carotenoid (2R, 6R, 2′R, 6′R)-decaprenoxanthin ( 1 ) starting from (-)-β-pinene ((S)- 2 ) is reported.     

C45- und C50-Carotinoide. 5. Mitteilung

C₄₅- and C₅₀-Carotenoids. Synthesis of an Optically Active Cyclic C₂₀-Building Block and of (2R,2′S)-3′,4′-Didehydro-1′,2′-dihydro-2-(4-hydroxy-3-methylbut-2-enyl)-2′-(3-methylbut-2-enyl)-β,ψ-caroten-1′-ol (= C. p. 473) The synthesis of the optically active C₂₀-building block (R)- 16 and of the optically active C₅₀-carotenoid C.p. 473 ( 1 ) starting from (?)-β-pinene is reported.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. IX. Synthese von (3R)-Hydroxyechinenon, (3R, 3′R)- und (3R, 3′S)-Adonixanthin, (3R)-Adonirubin,deren optischen Antipoden und verwandten Verbindungen

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. IX. Synthesis of (3R)-Hydroxyechinenone, (3R, 3′R)- and (3R, 3′S)-Adonixanthin, (3R)-Adonirubin, Their Optical Antipodes and Related Compounds The synthesis of racemic and optically active hydroxyechinenone ( 12–14 ), adonixanthin ( 16–19 ), adonirubin ( 22–24 ), meso-astaxanthin ( 26 ) and their corresponding diosphenols 15, 20, 21, 25, 27, 28 , and 29 ) by Wittig reaction is reported, starting from suitable C₁₅-phosphonium salts and C₁₀-aldehydes.     

Synthese von diastereo- und enantio-selektiv deuterierten β,ε-, β,β-, β,γ- und γ,γ-Carotinen

Synthesis of Diastereo- and Enantioselectively Deuterated β,ε-, β,β-, β,γ- and γ,γ-Carotenes We describe the synthesis of (1′R, 6′S)-[16′, 16′, 16′-²H₃]-β, εcarotene, (1R, 1′R)-[16, 16, 16, 16′, 16′, 16′-²H₆]-β, β-carotene, (1′R, 6′S)-[16′, 16′, 16′-²H₃]-γ, γ-carotene and (1R, 1′R, 6S, 6′S)-[16, 16, 16, 16′, 16′, 16′-²H₆]-γ, γ-carotene by a multistep degradation of (4R, 5S, 10S)-[18, 18, 18-²H₃]-didehydroabietane to optically active deuterated β-, ε- and γ-C₁₁-endgroups and subsequent building up according to schemes \documentclass{article}\pagestyle{empty}\begin{document}${\rm C}_{11} \to {\rm C}_{14}^{C_{\mathop {26}\limits_ \to }} \to {\rm C}_{40} $\end{document} and C₁₁ → C₁₄; C₁₄+C₁₂+C₁₄→C₄₀. NMR.- and chiroptical data allow the identification of the geminal methyl groups in all these compounds. The optical activity of all-(E)-[²H₆]-β,β-carotene, which is solely due to the isotopically different substituent not directly attached to the chiral centres, is demonstrated by a significant CD.-effect at low temperature. Therefore, if an enzymatic cyclization of [17, 17, 17, 17′, 17′, 17′-²H₆]lycopine can be achieved, the steric course of the cyclization step would be derivable from NMR.- and CD.-spectra with very small samples of the isolated cyclic carotenes. A general scheme for the possible course of the cyclization steps is presented.     

C45- and C50-Carotinoide. 1. Mitteilung. Synthese von (R)- and (S)-Lavandulol

C₄₅- and C₅₀-Carotenoids, 1st Communication. Synthesis of (R)- and (S)-Lavandulol Starting with methyl (3 R)-3-hydroxybutanoate ((R)-7) and ethyl (3 S)-3- hydroxybutanoate ((S)- 11 ), respectively, (R)- and (S)-lavandulol ((R)- 1 and (S)- 1 ) were synthesized with high optical purity. The synthesized key intermediates (R)- 6 and (S)- 6 are suitable compounds for the synthesis of optically active acyclic C₄₅- and C₅₀-carotenoids.     

Microbial reduction of α-acetyl-γ-butyrolactone

Isomers of α-1′-hydroxyethyl-γ-butyrolactone can be considered as potential GHB receptor ligands designed by the molecular hybridization of GLB 2 and GHV 4. Using Aspergillus niger, Geotrichum candidum, and Kluyveromyces marxianus, it was possible to obtain (+)-(3R,1′S)-α-1′-hydroxyethyl-γ-butyrolactone in good to excellent conversions, diastereoisomeric and enantiomeric excesses. The corresponding enantiomer, (−)-(3S,1′S)-α-1′-hydroxyethyl-γ-butyrolactone was also produced in good conversion, and diastereoisomeric and enantiomeric excesses using Hansenula sp.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. VII. Synthese von (3R)-3-Hydroxyretinol, (3R)-3-Hydroxyretinal und (3R)-3-Hydroxyretinsäure

Synthesis of optically active natural carotenoids and structurally related compounds. VII. Synthesis of (3R)-3-hydroxyretinol, (3R)-3-hydroxyretinal and (3R)-3-hydroxyretinoic acid The synthesis of (3R)-3-hydroxyretinol, ( 7 ), (3R)-3-hydroxyretinal ( 9 ) and (3R)-3-hydroxyretinoic acid ( 5 ) according to the building principle C₁₅ + C₅ = C₂₀ is reported utilizing the optically active C₁₅-phosphonium salt 2 and the C₅-aldehyde ester 3 .     

Synthesen von enantiomerenreinen Apoviolaxanthin-säuren, -olen und -alen (Persicaxanthin,Sinensiaxanthin und β-Citraurin-epoxid) und ihrer furanoiden Umlagerungsprodukte

Synthesis of Enantiomerically Pure Apoviolaxanthinoic Acids, Apoviolaxanthinols, and Apoviolaxanthinals (Including Persicaxanthin, Sinensiaxanthin, and β-Citraurin Epoxide) and of their Furanoid Rearrangement Products Starting from (1′S,2′R,4′S,2E,4E)-5-(1′,2′-epoxy-4′-hydroxy-2′,6′,6′-trimethylcyclohexy1)-3-methy1-2,4-pentadienal ( 3 ), a recently described synthon [6], a full range of C₂₀-, C₂₅-, C₂₇-, and C₃₀-polyenic acids, alcohols, and aldehydes and their (8R)- and (8S)-diastereoisomeric furanoid rearrangement products was prepared. The synthetic C₂₅-alcohols proved to be identical with persicaxanthin (= 12′-apoviolaxanthin-12′-ol) and perisicachromes (= 12′-apoauroxanthin-12′-ols) and the C₂₇-alcohols analogously with sinensiaxanthin and sinensiachromes. A correlation between the sign of the Cotton effects in the CD spectra of 5,6-and 5,8-epoxides and their configuration at C(6) and C(8), respectively, was established.     

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.     

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus Oxo-isophoron. I. Modifizierung der Kienzle-Mayer-Synthese von (3S 3′S)-Astaxanthin

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone. I. Modification of the Kienzle-Mayer-Synthesis of (3S, 3′S)-Astaxanthin An efficient synthesis of (3S, 3′S)-astaxanthin ( 1a ) in high yield and optical purity starting from (4R, 6R)-4-hydroxy-2,2,6-trimethylcyclohexanone ( 4 ) is reported. The absolute configuration of 1a , previously derived from ORD. data, has been confirmed by X-ray analysis of 5 , a derivative of 6-oxo-isophorone ( 2 ). The key features of the improved synthesis are the two-step conversion of 4 to the key intermediate (4S)-2,6,6-trimethyl-4-hydroxy-2-cyclohexen-1-one ( 14 ), a new method for the partial reduction of the sterically hindered triple bond of (S)-6-hydroxy-3-(5-hydroxy-3-methyl-3-penten-1-ynyl)-2,4,4-trimethyl-2-cyclohexen-1-one ( 32 ), and Wittig olefination of the dialdehyde 1,6-dimethyl-1,3,5-octatrienedial ( 38 ) using phosphonium salt 37 with a free hydroxyl group.     

(5R,6S,5′R,6′S)-5,6,5′,6′-Diepoxy-β,β-cartin: Sythese,Spectroskopische, chiroptische und chromatographische Eigenschaften

(5R,6S,5′R,6′S)-5,6,5′,6′-Diepoxy-β,β-Carotene: Synthesis, Spectroscopical and Chiroptical Properties, and HPLC-Behaviour Using the scheme C₁₃ + C₂→C₁₅ + C₁₀→C₄₀, whereby C₁₃ = (5R,6S)-5,6-epoxy-β-ionone [8], the title compound 11a , (R = H), has been prepared and characterized. It exhibits nearly identical CD spectra as violaxanthin ( 11b , R = OH).     

Synthesis of (5R)- and (5S)-5-Methyl-5, 6-dihydrouridine Derivatives

The hydrogenation of 2′, 3′-O-isopropylidene-5-methyluridine (1) in water over 5% Rh/Al₂O₃ gave (5 R)- and (5 S)-5-methyl-5, 6-dihydrouridine (2) , separated as 5′-O-(p-tolylsulfonyl)- (3) and 5′-O-benzoyl- (5) derivatives by preparative TLC. on silica gel and ether/hexane developments. The diastereoisomeric differentiation at the C(5) chiral centre depends upon the reaction media and the nature of the protecting group attached to the ribosyl moiety. The synthesis of iodo derivatives (5 R)- and (5 S)- 4 is also described. The diastereoisomers 4 were converted into (5 R)- and (5 S)-2′, 3′,-O-isopropylidene-5-methyl-2, 5′-anhydro-5, 6-dihydrouridine (7) .     

Enantioselektive Synthese von α-Phosphinoketonen. Vorläufige Mitteilung

Enantioselective Synthesis of α-Phosphinoketones The first asymmetric (C? P)-connective synthesis of α-phosphinoketones in high enantiomeric purity (e.e.91–97%) is described. Key step is the highly diastereoselective phosphinylation of SAMP-hydrazones (S)- 2 to produce α-phosphinohydrazones (S,R)- 3 , isolated as the more stable borane adducts. Subsequent ozonolysis afforded the title compounds (R)- 4 , potential ligands for enantioselective homogeneous catalysis.     

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].     

C45- and C50-Carotehoids. Part 8. Synthesis of (all-E,2S,2′S)-bacterioruberin, (all-E,2S,2′S)-monoanhydrobacterioruberin, (all-E,2S,2′S)-bisanhydrobacterioruberin, (all- E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydro- bacterioruberin,and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin

Starting from (R)-3-hydroxybutyric acid ((R)- 10 ) the C₄₅- and C₅₀-carotenoids (all-E,2S,2′S)-bacterioruberm ( 1 ), (all-E,2S,2′S)-monoanhydrobacterioruberin ( 2 ), (all-E,2S,2′S)-bisanhydrobacterioruberin ( 3 ), (all-E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydrobacterioruberin ( 5 ), and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin ( 6 ) were synthesized. By comparison of the chiroptical data of the natural and the synthetic compounds, the (2S)- and (2′S)-configuration of the natural products 1–3 and 6 was established.