54625-15-9Relevant articles and documents
Thermal Decomposition of Tricarbonyliron Lactone Complexes
Annis, Gary D.,Ley, Steven V.,Self, Christopher R.,Sivaramakrishnan, Ramamoorthy
, p. 299 (1980)
Tricarbonyliron lactones, on warming in tetrahydrofuran or benzene, afford products derived from decarbonylation, decarboxylation, and rearrangement pathways.
Efficient Access to All-Carbon Quaternary and Tertiary α-Functionalized Homoallyl-type Aldehydes from Ketones
Pace, Vittorio,Castoldi, Laura,Mazzeo, Eugenia,Rui, Marta,Langer, Thierry,Holzer, Wolfgang
supporting information, p. 12677 - 12682 (2017/09/08)
β,γ-Unsaturated aldehydes with all-carbon quaternary or tertiary α-centers were rapidly assembled from ketones through a unique synthetic operation consisting of 1) C1 homologation, 2) Lewis acid mediated epoxide–aldehyde isomerization, and 3) electrophilic trapping. The synthetic equivalence of a vinyl oxirane and a β,γ-unsaturated aldehyde is the key concept of this previously undisclosed tactic. Mechanistic studies and labeling experiments suggest that an aldehyde enolate is a crucial intermediate. The homologating carbenoid formation plays a critical role in determining the chemoselectivity.
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
supporting information, 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.
