Recent developments in the stereoselective synthesis of α-aminoacids

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

Asymmetric catalysts, either chemical or biological, effect the reactions of enantiomeric substrates at unequal rates, allowing for the kinetic resolution of racemates. The asymmetric reaction of chirally labile compounds capable of undergoing in situ racemization can, in principle, afford a single stereoisomer in 100% ee and in 100% yield. The second-order reaction provides a powerful tool for the stereoselective synthesis of chiral compounds, as exemplified by, among others, the biochemical hydrolysis of hydantoins or oxazolinones and microbial reductions or BINAP–Ru(II) catalyzed hydrogenation of certain α-substituted β-keto esters. Such transformations are characterized by the presence of parallel reactions interrelated by the stereoinversion of the enantiomeric substrates. The efficiency is decisively affected by the kinetic parameters, particularly the relative rates of the stereoinversion and reaction as well as the intrinsic stereochemical parameters of the catalyst and substrate. Such stereoselec...

Stereoselective Organic Synthesis via Dynamic Kinetic Resolution

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

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

The production of (S)-ethyl 3-hydroxybutyrate (2) from ethyl acetoacetate (1) in higher yields and with higher optical purity than with the usual procedures was achieved by continuous addition of the substrate 1 and sucrose to an aerated suspension of bakers' yeast. The microbial reduction of 1 by the fungus Geotrichum candidumLINK yields - for the first time - the antipode 3.

Production of (+)‐(S)‐Ethyl 3‐Hydroxybutyrate and (‐)‐(R)‐Ethyl 3‐Hydroxybutyrate by Microbial Reduction of Ethyl Acetoacetate

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

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

Hans Georg Wilhelm Leuenberger

Papers

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

Production of (+)‐(S)‐Ethyl 3‐Hydroxybutyrate and (‐)‐(R)‐Ethyl 3‐Hydroxybutyrate by Microbial Reduction of Ethyl Acetoacetate

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

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

Production of (+)‐(s)‐ethyl 3‐hydroxybutyrate and (‐)‐(r)‐ethyl 3‐hydroxybutyrate by microbial reduction of ethyl acetoacetate