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Upstream product

• 6890-93-3 4-((1E,3E,5E,7E)-9-Hydroxy-3,7-dimethyl-nona-1,3,5,7-tetraenyl)-3,5,5-trimethyl-cyclohex-3-enol 
• 6890-93-3 4-((1E,3E,5E,7E)-9-Hydroxy-3,7-dimethyl-nona-1,3,5,7-tetraenyl)-3,5,5-trimethyl-cyclohex-3-enol 
• 40835-18-5 methyl (E)-3-formylcrotonate 
• 120657-96-7 ethyl 3-tert-butyldimethylsilyloxy-β-ionylideneacetate 
• 76686-34-5 (2E,4E,6E,8E)-9-(4-Hydroxy-2,6,6-trimethyl-cyclohex-1-enyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid ethyl ester 
• 81555-38-6 ethyl 3-tert-butyldimethylsilyloxyretinoate 
• 15486-31-4 (2E,4E,6E,8E,10E,12E,14E)-15-(4-hydroxy-2,6,6-trimethylcyclohex-1-en-1-yl)-4,9,13-trimethylpentadeca-2,4,6,8,10,12,14-heptaenal 
• 650-69-1 3-hydroxy-apo-8'-carotenal 
• 60046-52-8 all-trans-(3R)-3-Hydroxyretinol 
• 41891-38-7 3-formyl crotonic acid ethyl ester 
• 116-26-7 safranal 
• 144-68-3 zeaxanthin 
• 127-40-2 lutein 
• 121429-38-7 (E)-3-[(S)-4-(tert-Butyl-dimethyl-silanyloxy)-2,6,6-trimethyl-cyclohex-1-enyl]-propenal 

Relevant academic research and scientific papers

The Structural and Biochemical Basis of Apocarotenoid Processing by β-Carotene Oxygenase-2

In mammals, carotenoids are converted by two carotenoid cleavage oxygenases into apocarotenoids, including vitamin A. Although knowledge about β-carotene oxygenase-1 (BCO1) and vitamin A metabolism has tremendously increased, the function of β-carotene oxygenase-2 (BCO2) remains less well-defined. We here studied the role of BCO2 in the metabolism of long chain β-apocarotenoids, which recently emerged as putative regulatory molecules in mammalian biology. We showed that recombinant murine BCO2 converted the alcohol, aldehyde, and carboxylic acid of a β-apocarotenoid substrate by oxidative cleavage at position C9,C10 into a β-ionone and a diapocarotenoid product. Chain length variation (C20 to C40) and ionone ring site modifications of the apocarotenoid substrate did not impede catalytic activity or alter the regioselectivity of the double bond cleavage by BCO2. Isotope labeling experiments revealed that the double bond cleavage of an apocarotenoid followed a dioxygenase reaction mechanism. Structural modeling and site directed mutagenesis identified amino acid residues in the substrate tunnel of BCO2 that are critical for apocarotenoid binding and catalytic processing. Mice deficient for BCO2 accumulated apocarotenoids in their livers, indicating that the enzyme engages in apocarotenoid metabolism. Together, our study provides novel structural and functional insights into BCO2 catalysis and establishes the enzyme as a key component of apocarotenoid homeostasis in mice.

COMPOUNDS AND METHODS OF TREATING OCULAR DISORDERS

A method of treating an ocular disorder in a subject associated with increased all-trans-retinal in an ocular tissue includes administering to the subject a therapeutically effective amount of a primary amine compound of formula (I); and pharmaceutically acceptable salts thereof.

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.

The Mycobacterium tuberculosis ORF Rv0654 encodes a carotenoid oxygenase mediating central and excentric cleavage of conventional and aromatic carotenoids

Mycobacterium tuberculosis, the causative agent of tuberculosis, is assumed to lack carotenoids, which are widespread pigments fulfilling important functions as radical scavengers and as a source of apocarotenoids. In mammals, the synthesis of apocarotenoids, including retinoic acid, is initiated by the β-carotene cleavage oxygenases I and II catalyzing either a central or an excentric cleavage of β-carotene, respectively. The M. tuberculosis ORF Rv0654 codes for a putative carotenoid oxygenase conserved in other mycobacteria. In the present study, we investigated the corresponding enzyme, here named M. tuberculosis carotenoid cleavage oxygenase (MtCCO). Using heterologously expressed and purified protein, we show that MtCCO converts several carotenoids and apocarotenoids in vitro. Moreover, the identification of the products suggests that, in contrast to other carotenoid oxygenases, MtCCO cleaves the central C15-C15' and an excentric double bond at the C13-C14 position, leading to retinal (C20), β-apo-14'-carotenal (C22) and β-apo-13-carotenone (C18) from β-carotene, as well as the corresponding hydroxylated products from zeaxanthin and lutein. Moreover, the enzyme cleaves also 3,3'-dihydroxy-isorenieratene representing aromatic carotenoids synthesized by other mycobacteria. Quantification of the products from different substrates indicates that the preference for each of the cleavage positions is determined by the hydroxylation and the nature of the ionone ring. The data obtained in the present study reveal MtCCO to be a novel carotenoid oxygenase and indicate that M. tuberculosis may utilize carotenoids from host cells and interfere with their retinoid metabolism. 2010 The Authors Journal compilation

Synthesis of enantiopure C3- and C4-hydroxyretinals and their enzymatic reduction by ADH8 from Xenopus laevis

(R)-all-trans-3-hydroxyretinal 1, (S)-all-trans-4-hydroxyretinal 3 and (R)-all-trans-4-hydroxyretinal 5 have been synthesized stereoselectively by Horner-Wadsworth-Emmons and Stille cross-coupling as bond-forming reactions. The CBS method of ketone reduct

SYNTHESIS OF OPTICALLY ACTIVE 3-DIAZOACETYLRETINALS WITH TRIISOPROPYLPHENYLSULFONYLHYDRAZONE

An improved synthesis of photoaffinity labeled, optically active retinal derivatives is presented.A stable, easy to handle, glyoxalic acid 2,4,6-triisopropylphenylsulfonylhydrazone (TIPPS) reacts with 3-hydroxyretinal to give the diazoacetylretinal analog in satisfactory yield.

156. Synthese von optisch aktiven, natuerlichen Carotinoiden und strukturell verwandten Naturprodukten. VII. Synthese von (3R)-3-Hydroxyretinol, (3R)-3-Hydroxyretinal und (3R)-Hydroxyretinsaeure

The synthesis of (3R)-hydroxyretinol (7), (3R)-3-hydroxyretinal (9) and (3R)-3-hydroxyretinoic acid (5) according to the building principle C15+C5=C20 is reported utilizing the optically active C15-phosphonium salt 2 and the C5-aldehyde ester 3.