Synthetic Scheme for the Preparation of <sup>13</sup>C‐Labeled 3,4‐Didehydro‐Retinal, 3‐Hydroxyretinal, and 4‐Hydroxyretinal up to Uniform <sup>13</sup>C‐Enrichment

Wijk, A.A.C. van; Weerd, Michiel B. van de; Lugtenburg, J.

doi:10.1002/ejoc.200390130

Cited by 10 publications

(12 citation statements)

References 19 publications

(19 reference statements)

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“…The [4,4΄-13 C 2 ]-and the other isotopologues of astaxanthin indicated in Scheme 9 have been prepared. In Scheme 10 it is shown that (4RS)-4hydroxy-β-cyclocitronitrile 42 is converted by acid catalyzed dehydration into the cyclohexadienenitrile 51 (van Wijk et al, 2003). Oxidation with m-CPBA acid results epoxidation of 3,4-double bond in product 52.…”

Section: Scheme 8 Preparation Of the End Group Of Canthaxanthin In Amentioning

confidence: 99%

Synthesis of highly 13C enriched carotenoids: access to carotenoids enriched with 13C at any position and combination of positions.

Lugtenburg¹,

Dawadi²

2012

Acta Biochim Pol

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Carotenoids and their metabolites are essential factors for the maintenance of important life processes such as photosynthesis. Animals cannot synthesize carotenoids de novo, they must obtain them via their food. In order to make intensive animal husbandry possible and maintain human and animal health synthetic nature identical carotenoids are presently commercially available at the multi-tonnes scale per year. Synthetically accessible (13)C enriched carotenoids are essential to apply isotope sensitive techniques to obtain information at the atomic level without perturbation about the role of carotenoids in photosynthesis, nutrition, vision, animal development, etc. Simple highly (13)C enriched C(1), C(2) and C(3) building blocks are commercially available via 99% (13)CO. The synthetic routes for the preparation of the (13)C enriched building blocks starting from the commercially available systems are discussed first. Then, how these building blocks are used for the synthesis of the various (13)C enriched carotenoids and apocarotenoids are reviewed next. The synthetic Schemes that resulted in (13)C enriched β-carotene, spheroidene, β-cryptoxanthin, canthaxanthin, astaxanthin, (3R,3'R)-zeaxanthin and (3R,3'R,6'R)-lutein are described. The Schemes that are reviewed can also be used to synthetically access any carotenoid and apocarotenoid in any (13)C isotopically enriched form up to the unitarily enriched form.

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Section: Scheme 8 Preparation Of the End Group Of Canthaxanthin In Amentioning

confidence: 99%

Synthesis of highly 13C enriched carotenoids: access to carotenoids enriched with 13C at any position and combination of positions.

Lugtenburg¹,

Dawadi²

2012

Acta Biochim Pol

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“…Besides 11- Z retinal in some animals (11 Z )-3,4-didehydroretinal, (3 R )-(11 Z )-3-hydroxyretinal and (4 R )-(11 Z )-4-hydroxyretinal are the chromophores of the visual pigment. The reactions depicted in the synthetic route in Scheme 18 are used for the preparation of above mentioned retinals [ 13 ]. α-Cyclocitronitrile 72 ( Scheme 17 and Scheme 18 ) is used as the starting material in which the double bond can easily be converted into an epoxide ring and subsequent treatment with a base gives ( R/S )-4-hydroxy unsaturated nitrile 73 .…”

Section: Isotope Enriched Chemically Modified Retinalsmentioning

confidence: 99%

“…Only in the case of amphibians and fresh water fish (11 Z )-3,4-didehydroretinal (also known as vitamin A 2 aldehyde) forms the chromophore. In some flies and insects the chromophore is (3R)-(11 Z )-3-hydroxyretinal and in squid it is (4 R )-(11 Z )-4-hydroxyretinal [ 13 , 14 ].…”

Section: Part a Introductionmentioning

confidence: 99%

Synthesis and Use of Stable Isotope Enriched Retinals in the Field of Vitamin A

Dawadi

Lugtenburg

2010

Molecules

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Abstract:The role of vitamin A and its metabolites in the life processes starting with the historical background and its up to date information is discussed in the introduction. Also the role of 11Z-retinal in vision and retinoic acid in the biological processes is elucidated. The essential role of isotopically enriched systems in the progress of vision research, nutrition research etc. is discussed. In part B industrial commercial syntheses of vitamin A by the two leading companies Hoffmann-La Roche (now DSM) and BASF are discussed. The knowledge obtained via these pioneering syntheses has been essential for the further synthetic efforts in vitamin A field by other scientific groups. The rest of the paper is devoted to the synthetic efforts of the Leiden group that gives an access to the preparation of site directed high level isotope enrichment in retinals. First the synthesis of the retinals with deuterium incorporation in the conjugated side chain is reviewed. Then, 13 C-labeled retinals are discussed. This is followed by the discussion of a convergent synthetic scheme that allows a rational access to prepare any isotopomer of retinals. The schemes that provide access to prepare any possible isotope enriched chemically modified systems are discussed. Finally, nor-retinals and bridged retinals that give access to a whole (as yet incomplete) library of possible isotopomers are reviewed.

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“…The spectral data of this compound were identical with those of the literature. 21 (2E,4E)-3-Methyl-5-(2,6,6-trimethyl-1,3-cyclohexadienyl)-2,4-pentadienal (10) To a solution of the nitrile 9 (244 mg, 1.14 mmol) in anhydrous dichloromethane (5 ml) was added a solution of DIBAL-H (1.0 M in hexane, 1.26 ml, 1.26 mmol) at 0°C and the resulting mixture was stirred for an additional 30 min. The reaction was quenched with moist silica gel (SiO 2 : H 2 O 5 : 1) and the resulting mixture was stirred for an additional 1 h. After filtration through Celite, the filtrate was dried over sodium sulfate.…”

Section: E4e)-3-methyl-5-(266-trimethyl-13-cyclohexadienyl)-24-mentioning

confidence: 99%

“…The spectral data of this compound were identical with those of the literature. 21 9-(2,6,6-trimethyl-1,3-cyclohexadien-1-yl)-2,4,6,8-nonatetraenenitrile (13) To a stirred suspension of NaH (60% oil dispersion, 18 mg, 0.45 mmol) in THF (5 ml) was added a solution of diphenyl phosphonate (11) (150 mg, 0.48 mmol) in THF (3 ml) was added at 0°C, and the resulting mixture was stirred for an additional 30 min. To this January 2008 113…”

Section: E4e)-3-methyl-5-(266-trimethyl-13-cyclohexadienyl)-24-mentioning

confidence: 99%

A Convenient and Stereoselective Synthesis of 11Z-3,4-Didehydroretinal by Horner-Emmons Reaction Using Diphenyl Phosphonate

Wada

Wang

Ito

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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In the visual pigment rhodopsin, the chromophore 11Z-retinal (1, vitamin A 1 aldehyde) binds to the e-amino group of a lysine residue of the apoprotein opsin through a protonated Schiff base.2) Rhodopsin is the G-protein-coupled photoreceptor in the retina of vertebrates that initiates the visual signal transduction cascade in dim light.3) It is a representative G-protein-coupled receptors (GPCRs), and is a member of the superfamily of the seven transmembrane helix proteins, a biologically very significant class of signal mediators.4,5) Some pigments, especially those of fresh water animals, contain 11Z-3,4-didehydroretinal (2, vitamin A 2 aldehyde) as well as 11Z-retinal (1) as the chromophore.6,7) For study of the mechanism of the visual process, a supply of a sufficient amount of the chromophore in pure 11Z-form is essential for the preparation of the pigment. Only one report for the stereoselective synthesis of 11Z-3,4-didehydroretinal (2) using hydrogenation of the acetylenic precursor by Lindlar catalyst has appeared in the literature. 8) In the past decade, methods dealing with a stereoselective synthesis of 11Z-retinal have been developed. [9][10][11] In connection with our stereoselective synthesis of retinoid compounds, 1,12-15) we describe herein a convenient and stereoselective synthesis of 11Z-3,4-didehydroretinal (2) (Chart 1). Results and DiscussionPreviously, we reported a highly stereoselective synthesis of 11Z-retinal (1) from the b-ionone-tricarbonyliron-complex (3) by controlling the stereochemistry of the newly produced double bond via the nitrile (4). 13) Our first approach for the preparation of 11Z-3,4-didehydroretinal (2) was an application of this methodology. However, all our attempts were unsuccessful. Treatment of 3,4-didehydro-b-ionone (7) 16) with dodecacarbonyltriiron in benzene afforded a complex mixture, and the desired tricarbonyliron-complex (8) was not obtained in good yield. The attempted conversion of the silyloxytricarbonyliron-complex (5), derived from 3-silyloxy-bionone, 17) into the 3,4-didehydro-b-ionone-tricarbonylironcomplex (8) was not achieved. Further more, our trials of transformation of the tricarbonyliron-complex (6), prepared according to our reported procedure, 13) into the 3,4-didehydroretinal (2), including the introduction of double bond at the 3 position, was not successful under the various reaction conditions (Chart 2).In the literature, two Horner-Emmons condensations, resulting in the formation of a new double bond predominantly A convenient synthesis of 3,4-didehydroretinal was developed. The Horner-Emmons reaction between 3,4-didehydro-b b-ionone and diphenyl phosphonate in the presence of crown ether gave the retinonitrile as an isomeric mixture, in which the newly produced double bond was predominantly 11Z-form. After separation of the 11Z-form retinonitrile, it was converted into the corresponding retinal in good yield without isomerization of the double bonds.

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Synthetic Scheme for the Preparation of ¹³C‐Labeled 3,4‐Didehydro‐Retinal, 3‐Hydroxyretinal, and 4‐Hydroxyretinal up to Uniform ¹³C‐Enrichment

Cited by 10 publications

References 19 publications

Synthesis of highly 13C enriched carotenoids: access to carotenoids enriched with 13C at any position and combination of positions.

Synthesis of highly 13C enriched carotenoids: access to carotenoids enriched with 13C at any position and combination of positions.

Synthesis and Use of Stable Isotope Enriched Retinals in the Field of Vitamin A

A Convenient and Stereoselective Synthesis of 11Z-3,4-Didehydroretinal by Horner-Emmons Reaction Using Diphenyl Phosphonate

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Synthetic Scheme for the Preparation of 13C‐Labeled 3,4‐Didehydro‐Retinal, 3‐Hydroxyretinal, and 4‐Hydroxyretinal up to Uniform 13C‐Enrichment

Cited by 10 publications

References 19 publications

Synthesis of highly 13C enriched carotenoids: access to carotenoids enriched with 13C at any position and combination of positions.

Synthesis of highly 13C enriched carotenoids: access to carotenoids enriched with 13C at any position and combination of positions.

Synthesis and Use of Stable Isotope Enriched Retinals in the Field of Vitamin A

A Convenient and Stereoselective Synthesis of 11Z-3,4-Didehydroretinal by Horner-Emmons Reaction Using Diphenyl Phosphonate

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Product

Resources

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Synthetic Scheme for the Preparation of ¹³C‐Labeled 3,4‐Didehydro‐Retinal, 3‐Hydroxyretinal, and 4‐Hydroxyretinal up to Uniform ¹³C‐Enrichment