24336-20-7

Upstream product

• 29706-61-4 9-cis-13-demethyl-retinal 
• 29706-62-5 11-cis-13-Demethylretinal 
• 82670-30-2 E-5,5-diethoxy-2-pentenal 
• 154141-24-9 6-bromo-1-ethoxyhexa-1Z,3E,5Z-triene 
• 129144-74-7 6-bromo-1,1-diethoxyhexa-3E,5Z-diene 
• 79-77-6 (E)-β-ionone 
• 3917-41-7 (2E,4E)-3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienal 
• 5299-98-9 (2E,4E)-3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-penta-2,4-dienenitrile 
• 129144-61-2 C₁₀H₁₇LiO₂ 
• 255387-05-4 6,6-diethoxy-1-bromohexa-3,5-diene 
• 138846-06-7 2-[(1’E,3’E)-3’-methyl-4’-iodobuta-1’,3’-dien-1’yl]-1,3,3-trimethylcyclohex-1-ene 
• 186895-65-8 Tributyl[(E,E)-5-hydroxypenta-1,3-dienyl]stannane 
• 209110-94-1 C₁₉H₃₆O₂Sn 
• 105175-91-5 3-methyl-5-(2’,6’,6’-trimethylcyclohex-1’-en-1’-yl)-penta-2,4-dienenitrile 

Downstream Products

• 29706-61-4 9-cis-13-demethyl-retinal 
• 29706-62-5 11-cis-13-Demethylretinal 
• 74311-19-6 (13Z)-13-Desmethylretinal 
• 69575-84-4 7-cis-13-demethylretinal 
• 73432-31-2 Butyl-[(2E,4E,6E,8E)-7-methyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraen-(E)-ylidene]-amine 

Relevant academic research and scientific papers

Synthesis of C11-to-C14 methyl-shifted all-: Trans -retinal analogues and their activities on human aldo-keto reductases

Human aldo-keto reductases (AKRs) are enzymes involved in the reduction, among other substrates, of all-trans-retinal to all-trans-retinol (vitamin A), thus contributing to the control of the levels of retinoids in organisms. Structure-activity relationship studies of a series of C11-to-C14 methyl-shifted (relative to natural C13-methyl) all-trans-retinal analogues as putative substrates of AKRs have been reported. The synthesis of these retinoids was based on the formation of a C10-C11 single bond of the pentaene skeleton starting from a trienyl iodide and the corresponding dienylstannanes and dienylsilanes, using the Stille-Kosugi-Migita and Hiyama-Denmark cross-coupling reactions, respectively. Since these reagents differ by the location and presence of methyl groups at the dienylorganometallic fragment, the study also provided insights into the ability of the different positional isomers to undergo cross-coupling and the sensitivity of these processes to steric hindrance. The resulting C11-to-C14 methyl-shifted all-trans-retinal analogues were found to be active substrates when tested with AKR1B1 and AKR1B10 enzymes, although relevant differences in substrate specificities were noted. For AKR1B1, all analogues exhibited higher catalytic efficiency (kcat/Km) than parent all-trans-retinal. In addition, only all-trans-11-methylretinal, the most hydrophobic derivative, showed a higher value of kcat/Km = 106 000 ± 23 200 mM-1 min-1 for AKR1B10, which is in fact the highest value from all known retinoid substrates of this enzyme. The novel structures, identified as efficient AKR substrates, may serve in the design of selective inhibitors with potential pharmacological interest. This journal is

Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration

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

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.

Reactivity of polyvinylogation: Easy and rapid access to different polyenals

This work describes the synthesis and the reactivity of three reagents of polyvinylogation 1-3. By condensation with several aldehydes and ketones, these reagents allow the introduction of three or four doubles bonds, leading to polyenals 5-6 in one or tw

Synthesis of specifically deuteriated 9- and 13-demethylretinals

(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

FUNCTIONALIZED VINYLIC ORGANOLITHIUM COMPOUNDS, SYNTHETIC EQUIVALENT OF ω-LITHIO SORBALDEHYDE.

Functional vinylic anions 2 and 3 react with aldehydes and ketones leading after hydrolysis to polyenic aldehydes 7.They have been used for the synthesis of navenone B 8.

Retinoids and Carotenoids, V.- Synthesis of Modified Retinals

The syntheses of 13-demethyl-13-ethyl-, 13-demethyl-13-propyl-, 13-demethyl-, 13-demethyl-14-methyl-, and 14-methylretinal are described.The UV spectra of some geometric isomers of these compounds are discussed.

Preparation of 11,14-epoxy-bridged and isomeric chain-demethylated retinals. 13-Demethyl-11,14-epoxy-, 9-demethyl-, 13-demethyl- and 9,13-bisdemethyl-retinals

9-Cis- and all-trans-13-demethyl-11,14-epoxyretinyl acetate were prepared via a Wittig coupling between β-ionylidenetriphenylphosphonium bromide (1) and 5-(acetoxymethyl)furfural.Saponification of these acetates, subsequent oxidation and HPLC separation a

Photochemistry of Linear Polyenes Related to Vitamin A. 13-Demethylretinal and 14-Methylretinal

The photochemistry of all-trans-13-demethylretinal (2) and all-trans-14-methylretinal (3) is examined in nonpolar and polar solvents.Upon extended irradiation into the first adsorption band, a photoequilibrium mixture is established that contains a number of isomeric photoproducts.High pressure liquid chromatographic methods are employed to isolate and purify each reaction product, and their adsorption spectral and photochemical properties are examined.Primary photoproducts and quantum yields (ψPI of trans -> cis or cis -> trans photoisomerization for all-trans-, 7-cis-, 9-cis-, and 11-cis-13- demethylretinal and all-trans-, 9-cis-, 11-cis-, and 13-cis-14-methylretinal are determined in a nonpolar solvent.The variation in ψPI and the relative photoproduct ratios of the isomers of 13-demethylretinal and 14-methylretinal differ from those of the corresponding isomers of retinal.The differences in quantum yields, primary products, and their relative ratios are analyzed in terms of the structural changes resulting from incorporation or removal of the alkyl substituent of the C-13-C-14 carbon-carbon double bond.

On the photoisomerisation of 13-desmethyl-retinal

All mono-cis-isomers of 13-desmethyl-retinal have been prepared fro the alll-trans-compound by photoisomerisation. The various isomers were separated by HPLC and identified by their 400 MHz-1NMR-spectra.