Synthesis of 9-CD3-9-cis-retinal cofactor of isorhodopsin

Abstract

We report the synthesis of 9-CD3-9-cis-retinal via a six-step procedure from β-ionone. The steps involve an initial deuteration of the methyl ketone of β-ionone followed by two consecutive Horner-Wadsworth-Emmons (HWE) coupling reactions and their corresponding DIBAL reductions. A final oxidation of the allylic alcohol of the retinol leads to the target compound. This deuterium labeled retinoid is an important cofactor for studying protein-retinoid interactions in isorhodopsin.

Human and animal cells under influence of different lighting and stimulus

“…Thus, finally we also know that opsins play an important role in taste and any form of chemical sensitivity [7] for example to detect not only light, but also thermal energy in Drosophila [8]. For vision formation, in the retina an opsin molecule absorbs a photon of light, that causes a change in retinal cofactor from 11-cis-retinal isomer to all-trans-retinal isomer [9] (Figure 1 B). This change in conformation of retinal pushes against the outer opsin protein to begin a signal cascade, which result in chemical signaling sent to the brain like an electrical signal which is translated in visual perception (Figure 1 C).…”

Detosylative (Deutero)alkylation of Indoles and Phenols with (Deutero)alkoxides

“…Isotope-labeled chemicals are valuable substances with extensive applications in various fields of chemistry and life sciences . Due to the better stability of carbon–deuterium bonds compared with carbon–hydrogen bonds, deuterium incorporation may exhibit the potential to alter the druglike properties of the parent compounds. , Given the prevalence of the NMe and OMe components in small-molecule pharmaceuticals, the synthesis of their trideuterated analogues becomes of particular importance with regard to further enhancing their biological properties, such as pharmacokinetics and pharmacodynamics, alongside their metabolic stability (Figure ). Furthermore, since deuterium is the cheapest and most accessible stable isotope, deuterium-labeled internal standards remain extremely useful in trace quantitative analyses of drugs in complex mixtures…”