Stereochemical Reassignment by Total Synthesis of an Ocular Pyridinium Bisretinoid of Retinal Pigment Epithelium Lipofuscin: iiso -A2E Is i -A2E
Year: 2025
Type: article
Abstract: The stereoselective synthesis of recently discovered lipofuscin fluorophore iiso -A2E, a C3,C4-bis-polyenylpyridinium salt derived from all- trans -retinal, which has been detected in human, pig, mouse, and bovine eyes, has been completed. The Suzuki–Miyaura cross-coupling reaction and Horner–Wadsworth–Emmons condensation were the key synthetic steps for the construction of the tetraenyl and pentaenyl arms, respectively, starting from a properly functionalized pyridine-3,4-dialdehyde surrogate, followed by pyridine alkylation. Subtle changes in the 1 H NMR and 13 C NMR spectra of the synthetic compound and natural compound suggested the structural revision of the latter, for which the C13′═C14′ E isomer at the longer C3-unsaturated pentaenyl chain of the pyridinium ring was proposed. The synthesis confirmed the alternative stereostructure of the natural pigment, which should be named i -A2E, thus correcting the double bond geometry of the natural fluorophore at C13′═C14′.
Source: Organic Letters
Authors: Brais Vidal, Oscar Iglesias-Menduiña, Belén Vaz, Rosana Álvarez, Claudio Martínez, Ángel R. de Lera
Institution: Universidade de Vigo
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4417005585