91013-15-9Relevant academic research and scientific papers
Broadening antifungal spectrum and improving metabolic stablity based on a scaffold strategy: Design, synthesis, and evaluation of novel 4-phenyl-4,5-dihydrooxazole derivatives as potent fungistatic and fungicidal reagents
Cheng, Maosheng,Cui, Hengxian,Jiang, Hong,Liu, Lei,Su, Xin,Sun, Yin,Wu, Tianxiao,Yin, Wenbo,Zhang, Yuxin,Zhao, Dongmei,Zhao, Liyu
, (2021/11/11)
5-phenylthiophene derivatives exhibited excellent antifungal activity against Candida albicans, Candida tropicalis and Cryptococcus neoformans. However, optimal compound 7 was inactive against Aspergillus fumigatus and unstable in human liver microsomes in vitro with a half-life of 18.6 min. To discover antifungal agents with a broad spectrum and improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of 4-phenyl-4,5-dihydrooxazole derivatives were designed and synthesized. It was especially encouraging that compound 22a displayed significant antifungal activities against eight susceptible strains and seven FLC-resistant strains. Furthermore, the potent compound 22a could prevent the formation of fungalbiofilms and displayed satisfactory fungicidal activity. In addition, the metabolic stability of compound 22a was improved significantly, with the half-life of 70.5 min. Compound 22a was almost nontoxic to mammalian A549, MCF-7, HepG2, and 293T cells. Moreover, pharmacokinetic studies in SD rats showed that compound 22a exhibited pharmacokinetic properties with a bioavailability of 15.22% and a half-life of 4.44 h, indicating that compound 22a is worthy of further study.
Enantioselective formation of tert-alkylamines by desymmetrization of 2-substituted serinols
Hong, Mi Sook,Kim, Tae Woo,Jung, Byunghyuck,Kang, Sung Ho
supporting information; experimental part, p. 3290 - 3296 (2009/04/10)
Novel enantioselective desymmetrization of 2-substituted 2-amino-1,3-propanediols has been established to generate asymmetric quaternary carbon centers comprising an amino group. Enantioselective as well as chemical conversion proved to be greatly dependent on the protecting group of the amino group in the substrate, desymmetrizing reagent, base, solvent, and naturally, catalyst. The highly effective desymmetrization has been implemented by using N-benzoylated substrates with benzoyl Chloride and triethylamine in the presence of tetraphenylbisoxazoline (24)-CuCl2 complex in THF at ambient temperature. An extensive survey of catalysts revealed that dimethylmalonate- bridged bisoxazoline-CuCl2 complexes were superior. Among them, the tetraphenylbisoxazoline (24)-CuCl2 complex turned out to work most efficiently with a wide array of the substrates. All the examined substrates, with the exception of 2-phenylserinol 36, were desymmetrized in the presence of 24-CuCl2 complex to give high enantioselectivities ranging from 85 to 95% ee. Complementary use of the diisopropylbisoxazoline (22)-CuCl2 complex has remedied the mediocre desymmetrization of 36 to give a significantly improved enantioselectivity from 63 to 83% ee.
