Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

We describe the development of an efficient method for the olefination of hydrazones and oximes.The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR 2 , OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes. Through this approach, we show that air-stable, commercially available ruthenium alkylidenes provide access to functionalized alkenes (20 examples) in ring-closing reactions with yields up to 88 %.

<div> <div> <p>Herein, we describe the application of Lewis acid-catalyzed carbonyl-olefin metathesis towards the synthesis of chiral, substituted tetrahydropyridines from commercially available amino acids as chiral pool reagents. This strategy relies on FeCl₃ as an inexpensive and environmentally benign catalyst and enables access to a variety of substituted tetrahydropyridines under mild reaction conditions. The reaction proceeds with complete stereoretention and is viable for a variety of natural and unnatural amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.</p> </div> </div> <br>

Herein we describe the application of Lewis-acidcatalyzed carbonyl−olefin metathesis toward the synthesis of substituted tetrahydropyridines from commercially available amino acids as chiral pool reagents. This strategy relies on FeCl 3 as an inexpensive and environmentally benign catalyst and enables access to a variety of substituted tetrahydropyridines under mild reaction conditions. The reaction proceeds with complete stereoretention and is viable for a variety of natural and unnatural amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.Letter pubs.acs.org/OrgLett

Carbonyl-olefin metathesis and carbonylalkyne metathesis represent established reactivity modes between carbonyls, alkenes, and alkynes under Lewis and Brønsted acid catalysis. Recently, an interrupted carbonyl-olefin metathesis reaction has been reported that results in tetrahydrofluorenes via a distinct fragmentation of the reactive intermediate. We herein report the development of an analogous transformation interrupting the carbonylalkyne metathesis reaction path resulting in dihydrofluorene products relying on Lewis acidic superelectrophiles as active catalytic species.

We describe the development of an efficient method for the olefination of hydrazones and oximes.The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR 2 , OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes. Through this approach, we show that air-stable, commercially available ruthenium alkylidenes provide access to functionalized alkenes (20 examples) in ring-closing reactions with yields up to 88 %.

Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4‐oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow‐up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4‐oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

Natural products have historically been am ajor source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products,with an unusual 4-oxazolidinone heterocycle at their core,r epresents an ew scaffold for antimicrobial discovery;h owever,q uestions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies.Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues to explore its active pharmacophore,a nd initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.