53018-97-6Relevant articles and documents
Synthesis of one double bond-inserted retinal analogs and their binding experiments with opsins: Preparation of novel red-shifted channelrhodopsin variants
Okitsu, Takashi,Yamano, Yumiko,Shen, Yi-Chung,Sasaki, Toshikazu,Kobayashi, Yuka,Morisawa, Shoko,Yamashita, Takahiro,Imamoto, Yasushi,Shichida, Yoshinori,Wada, Akimori
, p. 265 - 272 (2020/11/26)
In optogenetics, red-shifted channelrhodopsins (ChRs) are eagerly sought. We prepared six kinds of new chromophores with one double bond inserted into the polyene side chain of retinal (A1) or 3,4-didehy-droretinal (A2), and examined their binding efficie
Photocatalytic e → Z Isomerization of β-Ionyl Derivatives
Livingstone, Keith,Tenberge, Marius,Pape, Felix,Daniliuc, Constantin G.,Jamieson, Craig,Gilmour, Ryan
supporting information, p. 9677 - 9680 (2019/11/29)
An operationally simple E → Z isomerization of activated dienes, based on the β-ionyl motif intrinsic to retinal, is reported using inexpensive (-)-riboflavin (vitamin B2) under irradiation at 402 nm. Selective energy transfer from photoexcited (-)-riboflavin to the starting E-isomer enables geometrical isomerization. Since the analogous process with the Z-isomer is inefficient, microscopic reversibility is circumvented, thereby enabling a directional isomerization to generate the contra-thermodynamic product (up to 99% yield, up to 99:1 Z/E). Prudent choice of photocatalyst enables chemoselective isomerization to be achieved in both inter- and intramolecular systems. The principles established from this study, together with a molecular editing approach, have facilitated the development of a regioselective isomerization of a truncated triene based on the retinal scaffold.
Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration
Zhang, Jianye,Dong, Zhiqian,Mundla, Sreenivasa Reddy,Hu, X. Eric,Seibel, William,Papoian, Ruben,Palczewski, Krzysztof,Golczak, Marcin
, p. 477 - 491 (2015/01/30)
All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.
Synthetic control of retinal photochemistry and photophysics in solution
Bassolino, Giovanni,Sovdat, Tina,Liebel, Matz,Schnedermann, Christoph,Odell, Barbara,Claridge, Timothy D.W.,Kukura, Philipp,Fletcher, Stephen P.
, p. 2650 - 2658 (2014/03/21)
Understanding how molecular structure and environment control energy flow in molecules is a requirement for the efficient design of tailor-made photochemistry. Here, we investigate the tunability of the photochemical and photophysical properties of the retinal-protonated Schiff base chromophore in solution. Replacing the n-butylamine Schiff base normally chosen to mimic the saturated linkage found in nature by aromatic amines results in the reproduction of the opsin shift and complete suppression of all isomerization channels. Modification of retinal by directed addition or removal of backbone substituents tunes the overall photoisomerization yield from 0 to 0.55 and the excited state lifetime from 0.4 to 7 ps and activates previously inaccessible reaction channels to form 7-cis and 13-cis products. We observed a clear correlation between the presence of polarizable backbone substituents and photochemical reactivity. Structural changes that increase reaction speed were found to decrease quantum yields, and vice versa, so that excited state lifetime and efficiency are inversely correlated in contrast to the trends observed when comparing retinal photochemistry in protein and solution environments. Our results suggest a simple model where backbone modifications and Schiff base substituents control barrier heights on the excited-state potential energy surface and therefore determine speed, product distribution, and overall yield of the photochemical process.
New degradable alternating copolymers from naturally occurring aldehydes: Well-controlled cationic copolymerization and complete degradation
Ishido, Yasushi,Kanazawa, Arihiro,Kanaoka, Shokyoku,Aoshima, Sadahito
experimental part, p. 4060 - 4068 (2012/08/07)
Three naturally occurring conjugated aldehydes, (1R)-(-)-myrtenal, (S)-(-)-perillaldehyde, and β-cyclocitral, were cationically copolymerized with isobutyl vinyl ether using the EtSO3H/GaCl3 initiating system in the presence of 1,4-d
Synthesis, olfactory evaluation and determination of the absolute configuration of the β- and γ-Iralia isomers
Barakat, Assem,Brenna, Elisabetta,Fuganti, Claudio,Serra, Stefano
experimental part, p. 2316 - 2322 (2009/04/11)
The regioselective synthesis of the methyl-ionone isomers 6-9 is described. The enantiomers of the γ-isomers 8 and 9 are prepared by enzyme-mediated resolution of the corresponding 4-hydroxy derivatives followed by reductive elimination of the hydroxy group. The absolute configuration of the latter compound is determined by chemical correlation with the known α-isomers. Since all the isomers obtained are components of the artificial violet odourants sold under the trade name of Iralia, their odour properties are evaluated by professional perfumers.
Contribution of methyls in retinal side chain to regioselective photoisomerization of retinochromes
Tsujimoto, Kazuo,Sugiura, Jun'ichirou,Takemori, Nobuaki,Mizukami, Taku
, p. 1051 - 1052 (2007/10/03)
All-trans-9-demethyl-11-methylretinal was synthesized to elucidate the chromophoric interaction between hydrophobic part in retinochrome and 9-methyl substituent of retinal. Photoirradiation of its pigment efficiently gave the 11-cis-isomer in 90% regiose
Polyenylidene thiazolidine derivatives with retinoidal activities
Tashima, Toshihiko,Kagechika, Hiroyuki,Tsuji, Motonori,Fukasawa, Hiroshi,Kawachi, Emiko,Hashimoto, Yuichi,Shudo, Koichi
, p. 1805 - 1813 (2007/10/03)
Several polyenylidene thiazolidinedione or 2-thioxo-4-thiazolidinone derivatives were synthesized and their retinoidal activities were examined in terms of the differentiation-inducing ability towards human promyelocytic leukemia HL-60 cells and inhibitory effect on interleukin (IL)-1α-induced IL-6 production in MC3T3-E1 cells. Compounds containing a trimethylcyclohexenyl ring induced HL-60 cell differentiation with weaker activity than retinoic acid (1a) by one or two orders of magnitude. The thiazolidinedione derivatives (2, 5, 7) showed stronger activity than the corresponding 2-thioxo-4-thiazolidinone derivatives (3, 6, 8). The effects of a retinoid antagonist (LE540) and synergists (retinoid X receptor (RXR) agonists, HX600 or HX630) on the activities of thiazolidine derivatives indicate that these compounds elicit their activities through the nuclear retinoic acid receptors (RARs). All the thiazolidines examined also inhibited IL-1α-induced IL-6 production with IC50 values of 10nM order. The retinoidal activities of the thiazolidines are significant, considering that replacement of the carboxylic acid in retinoid structures with bioisosteric functional groups is generally ineffective, as seen in the structure-activity relationships of retinoidal benzoic acids.
Synthesis of specifically deuteriated 9- and 13-demethylretinals
Berg, Ellen M. M. van den,Bent, Arie van der,Lugtenburg, Johan
, p. 160 - 167 (2007/10/02)
(13-2H)13-Demethylretinal, (11,12,13-2H3)13-demethylretinal, (9-2H)9-demethylretinal and (9,10-2H2)9-demethylretinal were prepared in all-E, 9Z, 11Z and 13Z isomeric form with high deuterium incorporation.In the
Synthesis of 8-, 9-, 12-, and 13-mono-13C-retinal
Pardoen, J. A.,Mulder, P. P. J.,Berg, E. M. M. van den,Lugtenburg, J.
, p. 1431 - 1435 (2007/10/02)
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.
