Stereoselective Synthesis of Axially Chiral 5,5′-Linked bis-1-Arylisochromans with Antibacterial Activity

Czenke, ZoltánMándi, AttilaFedics, Gergely MiklósBarta, Roland AlbertKiss-Szikszai, AttilaKurucz-Szabados, AnnaTimári, IstvánBényei, AttilaKirály, Sándor BalázsOstorházi, EszterZhang, ChangshengKicsák, MátéKurtán, TiborCzenke Zoltán (1993-) (okleves vegyészmérnök, középiskolai kémiatanár)Kurtán Tibor (1973-) (vegyész, angol szakfordító)2025-08-162025-08-16International Journal Of Molecular Sciences. -26 : 16 (2025), p. 7777-. -Int. J. Mol. Sci. -1661-6596. -1422-00671661-6596. -1422-0067https://hdl.handle.net/2437/396887Inspired by naturally occurring bis-isochromans such as penicisteckins, we envisaged the first synthesis of biaryl-type bis-1-arylisochromans containing a stereogenic ortho-trisubstituted biaryl axis. We achieved the stereoselective synthesis of 5,5′-linked heterodimeric bis-isochromans containing both central and axial chirality elements by performing diastereoselective Suzuki–Miyaura biaryl coupling reactions on two optically active 1-arylpropan-2-ol derivatives, followed by two oxa-Pictet–Spengler cyclizations with aryl aldehydes or methoxymethyl chloride. We studied the diastereoselectivity of the cyclization step, separated the stereoisomeric products with chiral preparative HPLC and determined the absolute configuration through a combination of vibrational circular dichroism (VCD), NMR and single-crystal X-ray diffraction analysis. We demonstrated that different aryl groups could be introduced into the two isochroman subunits, since the dimethoxyaryl subunit reacted faster, enabling the two oxa-Pictet–Spengler cyclizations to be performed separately with different aryl aldehydes. We also explored the acid-catalyzed isomerization and oxidation to axially chiral ortho-quinones in order to produce stereoisomeric and oxidized analogs, respectively. We identified the antibacterial activity of our target bis-isochromans against Bacillus subtilis and Enterococcus faecalis with minimum inhibitory concentrations down to 4.0 and 0.5 μg/mL, respectively, which depend on the stereochemistry and substitution pattern of the bis-isochroman skeleton.idegen nyelvű folyóiratközlemény külföldi lapbanheterodimeric biaryl-type axially chiral bis-isochromansstereoselective Suzuki–Miyaura cross-couplingantibacterialvibrational circular dichroismchiral induction from central to axialstereoisomeric isochromans with central and axial chiralityaxially chiral ortho-quinonesStereoselective Synthesis of Axially Chiral 5,5′-Linked bis-1-Arylisochromans with Antibacterial Activityopen access articlehttps://ebib.lib.unideb.hu/ebib/CorvinaWeb?action=cclfind&resultview=long&ccltext=idno+BIBFORM131915https://www.mdpi.com/1422-0067/26/16/7777Szerző10.3390/ijms261677772025-08-16