- METHOD FOR SYNTHESIS OF 9-CIS-BETA-CAROTENE AND FORMULATIONS THEREOF
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The present invention relates to a method for total chemical synthesis of 9-cis-β-carotene (9CBC), and further provides stable formulations thereof.
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- A cross-metathesis approach to the synthesis of new etretinate type retinoids, ethyl retinoate and its 9Z-isomer
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Two aromatic retinoids were synthesized from styrene derivatives using a novel strategy with a cross-metathesis reaction as a key step. The biological activity of the new etretinate analogues was tested. Cross-metathesis reactions were also employed for the preparation of ethyl retinoate and its 9Z-isomer via the C15 + C5 route.
- Maj, Jadwiga,Morzycki, Jacek W.,Rárová, Lucie,Wasilewski, Grzegorz,Wojtkielewicz, Agnieszka
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supporting information
p. 5430 - 5433
(2012/11/07)
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- New syntheses of retinal and its acyclic analog γ-retinal by an extended aldol reaction with a C6 building block that incorporates a C5 unit after decarboxylation. A formal route to lycopene and β-carotene
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Since the C15 β-end-group aldehyde 10 ((β-ionylidene) acetaldehyde), an excellent intermediate in the syntheses of retinoids, can be synthesized in many ways from β-ionone, and since the corresponding acyclic C15 ψ-end-group aldehyde 5 can easily be synthesized from citral (1) (Scheme 3), we applied the C15 + C5 route to the syntheses of γ-retinal ((all-E)-8) (Scheme 3) and retinal ((all-E)-13) (Scheme 4), and therefore, by coupling (2 x C20 → C 40), to the preparation of lycopene (14) and β-carotene (15) (Scheme 5). Our new syntheses of retinal ((all-E)-13) and γ-retinal ((all-E)-8 use an extended aldol reaction with a C6 building block that incorporates a C5 unit after decarboxylation.
- Valla, Alain,Valla, Benoist,Le Guillou, Regis,Cartier, Dominique,Dufosse, Laurent,Labia, Roger
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p. 512 - 520
(2008/02/07)
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- Preparation and biological activity of 13-substituted retinoic acids
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13-Demethyl or 13-substituted all-E- and 9Z-retinoic acids were synthesized using a palladium-catalyzed coupling reaction of enol triflates and tributylstannylolefins. Their biological activities were then measured. The 13-ethyl analogs exhibited approximately one-half of the antiproliferative and differentiation-inducing activity of ATRA in HL-60 cells. In contrast, in the 9Z-derivatives, all analogs, except for the 13-butyl derivatives, showed apoptosis-inducing activity.
- Wada, Akimori,Fukunaga, Kouki,Ito, Masayoshi,Mizuguchi, Yukari,Nakagawa, Kimie,Okano, Toshio
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p. 3931 - 3942
(2007/10/03)
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- Synthesis of 9Z-9-substituted retinoic acids by palladium catalyzed coupling reaction of a vinyl triflate with alkenyl stannanes
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Palladium catalyzed cross coupling reactions of a vinyl triflate intermediate and various alkenyl stannanes afforded trisubstituted Z-olefins stereoselectively in high yields. These olefins were then converted to the corresponding 9Z-retinoic acids via Ho
- Wada,Nomoto,Tano,Yamashita,Ito
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p. 1391 - 1394
(2007/10/03)
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- Stereoselective synthesis of 9-cis-retinoic acid by Suzuki reaction
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The entire polyenic side chain of ethyl 9-cis-retinoate (7) has been stereoselectively synthesized and attached to the hydrophobic ring by a high-yielding thallium-accelerated Suzuki cross-coupling reaction. The Suzuki reaction partners, tetraenyl iodide 18 and alkenyl organoborane 19, are more conveniently used immediately after generation from their precursors. Alternative approaches using either the Stille reaction or a Suzuki reaction with a shorter polyenic component proved less efficient. The highly convergent sequence can be adapted to the preparation of analogs of 9-cis-retinoic acid (2), the natural ligand for the retinoid X (RXR) subfamily of nuclear receptors.
- Pazos, Yolanda,De Lera, Angel R.
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p. 8287 - 8290
(2007/10/03)
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- Synthesis of a new phospholipase A2 inhibitor of an aldehyde terpenoid and its possible inhibitory mechanism
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3-(E)Methoxycarbonyl-2,4,6-trienal compound A was stereoselectively synthesized and found to show strong inhibitory activity toward phospholipase A2 (PLA2) from bovine pancreas. As the inhibitory mechanism of PLA2 by A, the irreversible formation of dihydropyridine resulting from the reaction of A with lysine residues in PLA2 is proposed based on the model reactions.
- Tanaka, Katsunori,Kamatani, Mitsunobu,Mori, Hajime,Fujii, Shinobu,Ikeda, Kiyoshi,Hisada, Miki,Itagaki, Yasuhiro,Katsumura, Shigeo
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p. 1185 - 1188
(2007/10/03)
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- A Novel Method for a Stereoselective Synthesis of Trisubstituted Olefin Using Tricarbonyliron Complex: A Highly Stereoselective Synthesis of (all-E)- and (9Z)-Retinoic Acids
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In order to establish the stereoselective synthesis of retinoic acids, which are ligand molecules of the retinoic acid receptors (RARs, all-E-isomer) and the retinoid X receptors (RXRs, 9Z-isomer), the reaction of β-ionone-tricarbonyliron complex 7 with carbanions was investigated. Treatment of 7 with the lithium salt of acetonitrile afforded (7E,9E)-β-ionylideneacetonitrile-tricarbonyliron complex 8 exclusively, via addition, dehydration, and migration of tricarbonyliron complex. On the contrary, the reaction of 7 with the lithium enolate of ethyl acetate and subsequent dehydration by thionyl chloride afforded the ethyl (7E,9Z)-β-ionylideneacetate-tricarbonyliron complex 16b predominantly. These compounds (8 and 16b) were converted to the corresponding β-ionylidene-acetaldehyde-tricarbonyliron complexes (10 and 22) in excellent yields, respectively. The Emmons-Horner reaction of these compounds with C5-phosphonate followed by the sequence of decomplexation and alkaline hydrolysis gave the corresponding retinoic acids (26 and 29).
- Wada, Akimori,Hiraishi, Saeko,Takamura, Norio,Date, Tadamasa,Aoe, Keiichi,Ito, Masayoshi
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p. 4343 - 4348
(2007/10/03)
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- Stereoselective synthesis of 7E,9E- and 7E,9Z-β-ionylidene-acetaldehydes by use of tricarbonyl iron complex
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Stereoselective synthesis of 7E,9E- and 7E,9Z-β-ionylideneacetaldehydes was accomplished from the β-ionone tricarbonyl iron complex, and the latter was converted to 9Z-retinoic acid.
- Wada,Hiraishi,Ito
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p. 757 - 759
(2007/10/02)
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- Synthesis of High Specific Activity -9-cis-Retinoic Acid and Its Application for Identifying Retinoids with Unusual Binding Properties
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all-trans-Retinoic acid is known to bind to the retinoic acid receptors (RARs) resulting in an increase in their transcriptional activity.In contrast, recently identified 9-cis-retinoic acid (9-cis-RA), which is an additional endogenous RA isomer, is capable of binding to both RARs and retinoid X receptors (RXRs).These distinct properties have raised questions as to the biological role governed by these two retinoic acid isomers and the set of target genes that they regulate.Herein, we report the synthesis of high specific activity -9-cis-RA and its application to study the ligand-binding properties of the various retinoid receptor subtypes.We examined the binding properties of RARs and RXRs for a series of synthetic retinoids and compared the ligand-binding properties of these arotinoid analogs with their ability to regulate gene expression via the retinoid receptors in a cotransfection assay.The utilization of the -9-cis-RA competitive binding assay and the cotransfection assay has made it possible to rapidly identify important structural features of retinoids leading to increased selectivity for either the RAR or RXR receptor subtypes.
- Boehm, Marcus F.,McClurg, Michael R.,Pathirana, Charles,Mangelsdorf, David,White, Steven K.,et al.
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p. 408 - 414
(2007/10/02)
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- Polyvinylogation Reagents: 1-Lithio-4-trimethylsiloxy-penta-1,3-diene and 1-Lithio-4-ethoxy-2-methyl-buta-1,3-diene
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Title products, lithiodienol ethers 6a and 7a, synthetic equivalents of 4-lithio pent-3-ene-2-one and 4-lithio-senecialdehyde were obtained by bromine-lithium exchange.They are choice reagents for the transformations 1 -> 2 and 1 -> 3, respectively.
- Duhamel, Lucette,Ancel, Jean-Erick
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p. 9237 - 9250
(2007/10/02)
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- Dependence of the Triplet Potential of Retinal Homologues on the Chain Length: Resonance Raman Spectroscopy and Analysis of Triplet-Sensitized Isomerization
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The Raman spectra of triplet species produced from the all-trans, 7-cis and 9-cis isomers of β-ionylideneacetaldehyde (C15 aldehyde) and of β-ionylidenecrotonaldehyde (C17 aldehyde) were recorded.Each isomer of C15 aldehyde showed its own triplet Raman spectrum, while all the isomers of C17 aldehyde showed an identical triplet spectrum.The results were compared with those of isomeric retinal (C20 aldehyde) and retinylideneacetaldehyde (C22 aldehyde) obtained previously.Triplet-sensitized isomerization as well as direct photoisomerization of the all-trans isomer and the complete set of mono-cis isomers of C15, C17, C20, and C22 aldehydes were analyzed by HPLC.Mutual isomerization among the all-trans was seen for C17, C20, and C22 aldehydes.The quantum yield of triplet-sensitized isomerization for each isomer of the above aldehydes was determined. all the results are discussed in terms of triplet potentials with minima at cis and trans positions, the relative stability being dependent on the length of the polyene chain; the cis minima are as stable as the trans minimum for C15 aldehyde, while the cis minima are far less stable than the trans minimum for C17, C20, and C22 aldehydes.
- Mukai, Yumiko,Hashimoto, Hideki,Koyama, Yasushi
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p. 4042 - 4051
(2007/10/02)
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- β-Lactoglobulin Directed Photoisomerization of Retinal and Related Compounds
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The 11-cis enriched photostationary state mixture of retinal trapped in BLG, a water soluble protein, is similar to that of retinal in heptanol.The results, along with those of the lower homologs, are consistend with a model involving specific protein interaction with the cyclohexenyl portion of the substrate and remote protonation of the aldehyde carbonyl group.
- Li, Xiao-yuan,Asato, Alfred E.,Liu, R. S. H.
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p. 4841 - 4844
(2007/10/02)
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- UN NOUVEAU REACTIF DE PRENYLATION : LE LITHIO-1 METHYL-2 TRIMETHYLSILOXY-4 BUTADIENE
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This new reagent is obtained by bromine-lithium exchange using tertiobutyllithium in ether at -70 deg C.Its condensation with carbonyl compounds followed by hydrolysis in mild conditions leads to polyenals with good yields.Synthesis of retinal from β-ionylidenacetaldehyde is described.
- Duhamel, L.,Duhamel, P.,Lecouve, J.P.
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p. 4339 - 4348
(2007/10/02)
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- SYNTHETIC INVESTIGATIONS IN THE CHEMISTRY OF POLYENE COMPOUNDS. -- XLVIII. STRUCTURE AND TRANSFORMATIONS OF 12-CARBOXYRETINOIC ACIDS AND THEIR ESTERS. SYNTHESIS OF 13-CIS-RETINOIC ACID
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In reaction with ethyl β-methylglutaconate under the influence of alkali in methanol the Z and E isomers of β-ionylideneacetaldehyde form isomeric 9Z,11Z,13Z- and 9E,11Z,13Z-12-carboxyretinoic acids.Decarboxylation of the latter in the pyridine-piperidine system in the presence of copper salts leads to 13Z-retinoic acid and is accompanied by the formation of 9,13-dimethyl-7-(1,1,5-trimethyl-5-cyclohexen-6-yl)-7,9,11,13-octatetraene.The stereoisomeric transformations of 12-substituted 9E,Z,11Z,13Z-retinoic acids and the corresponding diols and diacetates obtained from them were investigated.Isomerization takes place at the double bond at the C9 atom and depends on the nature of the substituent at the C12 atom.
- Polyachenko, L. N.,Davydova, L. P.,Darskaya, E. N.,Filippova, T. M.,Samokhvalov, G. I.
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p. 685 - 694
(2007/10/02)
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- Synthesis of 8-, 9-, 12-, and 13-mono-13C-retinal
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The 8-, 9-, 12-, and 13-mono-13C-retinals were synthesized with >98percent chemical purity and 93percent 13C incorporation from 13C-labelled acetonitrile.Their 13C-13C and 13C-1H nmr coupling constants were determined.
- Pardoen, J. A.,Mulder, P. P. J.,Berg, E. M. M. van den,Lugtenburg, J.
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p. 1431 - 1435
(2007/10/02)
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- PHOTOISOMERIZATION OF THE C18 KETONE IN THE VITAMIN A SERIES. SOLVENT EFFECT ON PHOTOISOMERIZATION OF COMPOUNDS RELATED TO RETINAL
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The directions of photoisomerization of polyenals and polyenones are believed to be controlled by the relative ordering of n,?* and ?,?* states.
- Ramamurthy, V.,Denny, M.,Liu, R. S. H.
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p. 2463 - 2466
(2007/10/02)
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