A Short Diastereo- and Enantioselective Synthesis of cis-4,5-Disubstituted Oxazolidin-2-ones

Enders, Dieter; Kallfass, Ulrike; Nolte, Bert

doi:10.1055/s-2002-19341

Cited by 11 publications

(7 citation statements)

References 2 publications

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“…The coupling constant between the annular protons of H-2 and H-3 in 5 was 4.5 Hz. Since the respective coupling constants between the two annular protons of cis and trans isomers are generally 6–9 Hz and 4–6 Hz, respectively, the annular protons were likely to have been oriented to the trans position. NOE was not observed between H-2 and H-3, indicating that the relative stereochemistry is 2 S* , 3 R* .…”

Section: Resultsmentioning

confidence: 99%

Simplifungin and Valsafungins, Antifungal Antibiotics of Fungal Origin

et al. 2016

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The targets of antifungal antibiotics in clinical use are more limited than those of antibacterial antibiotics. Therefore, new antifungal antibiotics with different mechanisms of action are desired. In the course of our screening for antifungal antibiotics of microbial origins, new antifungal antibiotics, simplifungin (1) and valsafungins A (2) and B (3), were isolated from cultures of the fungal strains Simplicillium minatense FKI-4981 and Valsaceae sp. FKH-53, respectively. The structures of 1 to 3 including their absolute stereochemistries were elucidated using various spectral analyses including NMR and collision-induced dissociation (CID)-MS/MS as well as chemical approaches including modifications to the Mosher's method. They were structurally related to myriocin. They inhibited the growth of yeast-like and zygomycetous fungi with MICs ranging between 0.125 and 8.0 μg/mL. An examination of their mechanisms of action by the newly established assay using LC-MS revealed that 1 and 2 inhibited serine palmitoyltransferase activity, which is involved in sphingolipid biosynthesis, with IC50 values of 224 and 24 nM, respectively.

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Section: Resultsmentioning

confidence: 99%

Simplifungin and Valsafungins, Antifungal Antibiotics of Fungal Origin

et al. 2016

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“…1 H NMR (300 MHz, DMSO-d 6 ) δ 11.75 (br s, 1 H), 11.42 (br s, 1 H), 7.76 (s, 1 H), 5.23 (t, J = 5. 65…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Discovery of Novel DNA Gyrase Inhibiting Spiropyrimidinetriones: Benzisoxazole Fusion with N-Linked Oxazolidinone Substituents Leading to a Clinical Candidate (ETX0914)

et al. 2015

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A novel class of bacterial type-II topoisomerase inhibitor displaying a spiropyrimidinetrione architecture fused to a benzisoxazole scaffold shows potent activity against Gram-positive and fastidious Gram-negative bacteria. Here, we describe a series of N-linked oxazolidinone substituents on the benzisoxazole that improve upon the antibacterial activity of initially described compounds of the class, show favorable PK properties, and demonstrate efficacy in an in vivo Staphylococcus aureus infection model. Inhibition of the topoisomerases DNA gyrase and topoisomerase IV from both Gram-positive and a Gram-negative organisms was demonstrated. Compounds showed a clean in vitro toxicity profile, including no genotoxicity and no bone marrow toxicity at the highest evaluated concentrations or other issues that have been problematic for some fluoroquinolones. Compound 1u was identified for advancement into human clinical trials for treatment of uncomplicated gonorrhea based on a variety of beneficial attributes including the potent activity and the favorable safety profile.

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“…211 Following a four-step reaction sequence of R-alkylation, organolithium 1,2-addition (with later carbamate protection of the formed hydrazine), TBS-deprotective cyclization, and cleavage of the auxiliary, several cis-4,5-disubstituted oxazolidin-2-ones 267 (Scheme 51) were obtained in fair to good yields (27-78%) and in high diastereo-and enantiomeric purities (de 88% to >96%, ee > 96%). 212 …”

Section: R-alkylation Combined With 12-addition To the Hydrazonementioning

confidence: 99%