Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity was written by Svircev, Milos;Popsavin, Mirjana;Pavic, Aleksandar;Vasiljevic, Branka;Rodic, Marko V.;Djokic, Sanja;Kesic, Jelena;Sreco Zelenovic, Bojana;Popsavin, Velimir;Kojic, Vesna. And the article was included in Bioorganic Chemistry in 2022.Safety of (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol This article mentions the following:
The synthesis of several new goniofufurone bioisosteres was achieved in which the Ph residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine Et ester hydrochloride, followed by the subsequent reaction of resulting C-4′ epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumor cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This mol. exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the compounds antitumor agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR anal. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 μM. In the experiment, the researchers used many compounds, for example, (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol (cas: 582-52-5Safety of (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol).
(3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol (cas: 582-52-5) belongs to tetrahydrofuran derivatives.Tetrahydrofuran has many industry uses as a solvent including in natural and synthetic resins, high polymers, fat oils, rubber, polymer. It is more basic than diethyl ether and forms stronger complexes with Li+, Mg2+, and boranes. It is a popular solvent for hydroboration reactions and for organometallic compounds such as organolithium and Grignard reagents.Safety of (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem