Tetrahedron report number 203

Salmon farming increased substantially in the 1980s, which created a large market for astaxanthin, the principal pigment of salmon. Carotenoids are the most widely distributed class of pigments in ...

Astaxanthin from Microbial Sources

Enzymes as Catalysts in Synthetic Organic Chemistry [New Synthetic Methods (53)]

Lutein, Zeaxanthin, and meso-Zeaxanthin: The Basic and Clinical Science Underlying Carotenoid-based Nutritional Interventions against Ocular Disease

Asymmetric bioreduction of activated C=C bonds using enoate reductases from the old yellow enzyme family.

Synthesis of optically active natural carotenoids and structurally related compounds. I. Synthesis of the chiral key compound (4R, 6R)-4-hydroxy-2,2,6-trimethylcyclohexanone.



A technical synthesis of (4R, 6R)-4-hydroxy-2,2,6-trimethylcyclohexanone (7) starting from the readily available oxo-isophorone (2) is described. 7 is an ideal precursor for the synthesis of naturally occurring, optically active hydroxylated carotenoids (e.g. zeaxanthin, cryptoxanthin and structurally related compounds).



Chirality is introduced at C(6) by a stereoselective fermentative hydrogenation of the double bond using baker's yeast as the biocatalyst. Thereafter the carbonyl group at C(4) is reduced selectively and stereospecifically by chemical methods to the corresponding alcohol. Chemical reduction is preferably carried out by hydrogenation in the presence of a nickel catalyst or using triisobutylaluminium as the reducing agent. Stability, stereochemistry and physical properties of 7 and the stereoisomers thereof are discussed.

Synthese von optisch aktiven, natürlichen Carotinoiden und strukturell verwandten Naturprodukten. I. Synthese der chiralen Schlüsselverbindung (4R, 6R)‐4‐Hydroxy‐2,2,6‐trimethylcyclohexanon

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).

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

Starting from the readily available, optically active (4R)-hydroxy-2,2,6-trimethylcyclohexanone (2), a new technical synthesis of (3R,3′R)-zeaxanthin is described. According to a completely new C9+C2+C4 = C15 scheme, the ketone 2 was protected, ethynylated with Li-acetylide, and the C11-intermediate 6 was acetylated, followed by dehydration. The product 10 was protected, deprotonated, and subsequently reacted with methyl vinyl ketone to provide the C15-propargylate 13. Reduction in situ of 13 with Vitride yielded the olefinic C15-alcohol 11 which was transformed into the known C15-Wittig salt 3. A double Wittig reaction of this salt with the C10-dialdehyde 4 afforded nature-identical zeaxanthin (1).

Technical Procedures for the Syntheses of Carotenoids and Related Compounds from 6‐Oxo‐isophorone: Syntheses of (3R,3′R)‐Zeaxanthin. Part I

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone. III. A New Concept for the Synthesis of the Enantiomeric Astaxanthins



A new and efficient concept for the total synthesis of (3S, 3'S)- and (3R, 3'R)-astaxanthin (1a and 1c, resp.) in high overall yield and up to 99,2% enantiomeric purity is described. Key intermediates are the (S)- and (R)-acetals 10 and 17, respectively (Scheme 2). These chiral building blocks were synthesized via three different routes: a) functionalization of the enantiomeric 3-hydroxy-6-oxo-isophorons4) 2 and 11, respectively (Scheme 2); b) optical resolution of 3,4-dihydroxy-compound4) 19(Scheme 3), and c) fermentative reductions of 6-oxo-isophorone derivatives (Schemes 4 and 5). - The absolute configurations of the two intermediates 12 and 13(Scheme 2) have been confirmed by X-ray analysis. - The final steps leading to the enantiomeric astaxanthins are identical with those described for optically inactive astaxanthin [1].

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. II. Ein neues Konzept für die Synthese von (3RS, 3′RS)-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.

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

Reinhard Zell

Papers

Synthese von optisch aktiven, natürlichen Carotinoiden und strukturell verwandten Naturprodukten. I. Synthese der chiralen Schlüsselverbindung (4R, 6R)‐4‐Hydroxy‐2,2,6‐trimethylcyclohexanon

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

Technical Procedures for the Syntheses of Carotenoids and Related Compounds from 6‐Oxo‐isophorone: Syntheses of (3R,3′R)‐Zeaxanthin. Part I

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. II. Ein neues Konzept für die Synthese von (3RS, 3′RS)-Astaxanthin

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