3917-40-6Relevant articles and documents
Accurate measurements of 13C-13C J-couplings in the rhodopsin chromophore by double-quantum solid-state NMR spectroscopy
Lai, Wai Cheu,McLean, Neville,Gansmueller, Axel,Verhoeven, Michiel A.,Antonioli, Gian Carlo,Carravetta, Marina,Duma, Luminita,Bovee-Geurts, Petra H. M.,Johannessen, Ole G.,De Groot, Huub J. M.,Lugtenburg, Johan,Emsley, Lyndon,Brown, Steven P.,Brown, Richard C. D.,DeGrip, Willem J.,Levitt, Malcolm H.
, p. 3878 - 3879 (2007/10/03)
A new double-quantum solid-state NMR pulse sequence is presented and used to measure one-bond 13C-13C J-couplings in a set of 13C2-labeled rhodopsin isotopomers. The measured J-couplings reveal a perturbation of the electronic structure at the terminus of the conjugated chain but show no evidence for protein-induced electronic perturbation near the C11-C12 isomerization site. This work establishes NMR methodology for measuring accurate 1JCC values in noncrystalline macromolecules and shows that the measured J-couplings may reveal local electronic perturbations of mechanistic significance. Copyright
Palladium-catalyzed coupling reaction of an enol nonaflate with (vinyl)tributylstannanes and acetylenes: A highly stereoselective synthesis of 8,18-13C2-labeled retinal
Wada, Akimori,Ieki, Yasuhiro,Nakamura, Saeko,Ito, Masayoshi
, p. 1581 - 1588 (2007/10/03)
Here we report that enol nonaflates exhibit higher reactivity than the corresponding enol triflates in palladium-catalyzed cross-coupling reactions with various (vinyl)tributylstannanes and acetylenes. We also highlight the reaction of a vinyl nonaflate,
Preparation and biological activity of 13-substituted retinoic acids
Wada, Akimori,Fukunaga, Kouki,Ito, Masayoshi,Mizuguchi, Yukari,Nakagawa, Kimie,Okano, Toshio
, p. 3931 - 3942 (2007/10/03)
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.
Palladium catalyzed coupling reaction of an enol nonaflate with (vinyl)tributylstannanes and acetylenes
Wada, Akimori,Ieki, Yasuhiro,Ito, Masayoshi
, p. 1061 - 1064 (2007/10/03)
A novel method for a stereoselective synthesis of trienes and dienynes was developed by palladium catalyzed cross coupling reactions of an enol nonaflate with (vinyl)tributylstannanes and acetylenes in good to excellent yields. Here, the enol nonaflate ex
Constraints of opsin structure on the ligand-binding site: Studies with ring-fused retinals
Hirano, Takahiro,Lim, In Taek,Kim, Don Moon,Zheng, Xiang-Guo,Yoshihara, Kazuo,Oyama, Yoshiaki,Imai, Hiroo,Shichida, Yoshinori,Ishiguro, Masaji
, p. 606 - 615 (2007/10/03)
Ring-fused retinal analogs were designed to examine the hulatwist mode of the photoisomerization of the 9-cis retinylidene chromophore. Two 9-cis retinal analogs, the C11-C13 five-membered ring-fused and the C12-C14 five-membered ring-fused retinal derivatives, formed the pigments with opsin. The C11-C13 ring-fused analog was isomerized to a relaxed all-trans chromophore (λmax > 400 nm) at even - 269°C and the Schiff base was kept protonated at 0°C. The C12-C14 ring-fused analog was converted photochemically to a bathorhodopsin-like chromophore (λmax = 583 nm) at -196°C, which was further converted to the deprotonated Schiff base at 0°C. The model-building study suggested that the analogs do not form pigments in the retinal-binding site of rhodopsin but form pigments with opsin structures, which have larger binding space generated by the movement of transmembrane helices. The molecular dynamics simulation of the isomerization of the analog chromophores provided a twisted C11-C12 double bond for the C12-C14 ring-fused analog and all relaxed double bonds with a highly twisted C10-C11 bond for the C11-C13 ring-fused analog. The structural model of the C11-C13 ring-fused analog chromophore showed a characteristic flip of the cyclohexenyl moiety toward transmembrane segments 3 and 4. The structural models suggested that hula twist is a primary process for the photoisomerization of the analog chromophores.
Synthesis of 9Z-9-substituted retinoic acids by palladium catalyzed coupling reaction of a vinyl triflate with alkenyl stannanes
Wada,Nomoto,Tano,Yamashita,Ito
, p. 1391 - 1394 (2007/10/03)
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
Stereoselective synthesis of 9-cis-retinoic acid by Suzuki reaction
Pazos, Yolanda,De Lera, Angel R.
, p. 8287 - 8290 (2007/10/03)
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.
Stereoselective synthesis and receptor activity of conformationally defined retinoid X receptor selective ligands
Vuligonda, Vidyasagar,Garst, Michael E.,Chandraratna, Roshantha A.S.
, p. 589 - 594 (2007/10/03)
Retinoid X Receptor (RXR) specific ligands are currently being investigated for the treatment of metabolic diseases such as type II diabetes. We report the synthesis of conformationally locked retinoids, which are potent RXR selective ligands, and the att
Stereoselective synthesis of 7E,9E- and 7E,9Z-β-ionylidene-acetaldehydes by use of tricarbonyl iron complex
Wada,Hiraishi,Ito
, p. 757 - 759 (2007/10/02)
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.
Synthesis of High Specific Activity -9-cis-Retinoic Acid and Its Application for Identifying Retinoids with Unusual Binding Properties
Boehm, Marcus F.,McClurg, Michael R.,Pathirana, Charles,Mangelsdorf, David,White, Steven K.,et al.
, p. 408 - 414 (2007/10/02)
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.
