1. Efficient Total Synthesis of Lissodendrin B, 2-Aminoimidazole Marine Alkaloids Isolated from Lissodendoryx (Acanthodoryx) Fibrosa
Xianfeng Wei, Xuelong Hu, Rilei Yu, Shengbiao Wan, Tao Jiang Mar Drugs. 2019 Dec 31;18(1):36. doi: 10.3390/md18010036.
Lissodendrin B is a 2-aminoimidazole alkaloid bearing a (p-hydroxyphenyl) glyoxal moiety that was isolated from the Indonesian sponge Lissodendoryx (Acanthodoryx) fibrosa. We reported the first efficient total synthesis of Lissodendrin B. The precursor 4,5-disubstituted imidazole was obtained through Suzuki coupling and Sonogashira coupling reactions from 4-iodoimidazole. C2-azidation and reduction of the azide then provided the core structures of Lissodendrin B. Subsequent triple-bond oxidation, demethylation, and deacetylation gave the final product. The synthesis approach consists of ten steps with an overall yield of 1.1% under mild reaction conditions, and it can be applied for future analog synthesis and biological studies.
2. Solid-phase synthesis of 4-substituted imidazoles using a scaffold approach
E Gelens, W J Koot, W M Menge, H C Ottenheijm, H Timmerman Bioorg Med Chem Lett. 2000 Sep 4;10(17):1935-8. doi: 10.1016/s0960-894x(00)00363-2.
Immobilized 4-iodoimidazole 2 was used in a metal/halogen exchange reaction followed by treatment with electrophiles and subsequent cleavage from the resin to yield 4-substituted imidazoles 8-11. Grignard reaction with the resin-bound ketones 5 yielded the corresponding alcohols 11. This approach was used for a library synthesis of 35 imidazoles.
3. An expedient synthesis of flexible nucleosides via a regiocontrolled enzymatic glycosylation of functionalized imidazoles
S Vichier-Guerre, L Dugué, F Bonhomme, S Pochet Org Biomol Chem. 2017 Oct 4;15(38):8193-8203. doi: 10.1039/c7ob01850a.
A versatile two-step synthesis of C4- and C5-arylated 2'-deoxyribosylimidazoles was elaborated using enzymatic N-transglycosylation followed by microwave-assisted Pd-catalysed arylation reactions. We report herein the reaction conditions that permit managing regioselectivity (N3 versus N1-isomers) in the enzymatic glycosylation of 4-iodoimidazole using the nucleoside N-deoxyribosyltransferase from L. leichmannii. Regiocontrolled glycosylation was also observed among several other imidazole derivatives studied, providing simple access to isomers not readily accessible by chemical routes. Finally, a series of flexible nucleosides was obtained in one step from 4- or 5-iodo-imidazole nucleosides by the Suzuki-Miyaura cross-coupling reaction with (hetero)aryl-boronic acids in aqueous media. Moreover, this chemoenzymatic approach is compatible with a one-pot two-step process affording a straightforward access to a broad array of potential anticancer and antiviral drugs as well as new DNA building blocks.
