(4S)-p.Hydroxybenzyl-1,3-Oxazolidin-2-one as Solid Supported Chiral Auxiliary in Asymmetric 1,3-Dipolar Cycloadditions

Evans' chiral auxiliary was grafted onto both Merrifield and Wang resins and, after functionalisation, they were used as chiral dipolarophiles in a 1,3-dipolar cycloaddition involving both a nitrile oxide and a nitrone. The cycloadducts were cleaved and analysed by chiral HPLC: the recovered supported chiral oxazolidinone was functionalised and reused in further cycloadditions. The stereochemical results as well as the possibility of recycling the chiral linker supports the applicability of solid-supported chiral auxiliaries

Solid supported chiral auxiliaries in asymmetric synthesis. Part 2: Catalysis of 1,3-dipolar cycloadditions by Mg(II) cation

1,3-Dipolar cycloadditions of supported Evans' chiral auxiliary with nitrile oxides and nitrones in the presence of Mg(II) cation as catalyst were evaluated. The presence of acetonitrile as co-solvent was found to be fundamental for the Lewis acid catalysis on solid-phase. The regio- and stereochemical outcome of nitrile oxide cycloadditions is influenced by nearly stoichiometric quantities of the cation, whilst catalytic amounts of Mg(II) influence both the reactivity and the stereoselectivity of the nitrone cycloadditions. The results obtained support a reaction mechanism involving the coordination of the Mg(II) to the dicarbonyl fragment of the chiral auxiliary

Solid Supported Nitrile Oxides as Stable and Valuable Reactive Intermediates

1,3-Dipolar cycloadditions of Wang resin supported nitrile oxides have been performed with several dipolarophiles to afford 5-membered heterocycles in fair yields. The nitrile oxides displayed increased stability on the solid phase, allowing clean transformations into nitrosocarbonyl intermediates, which could be trapped with suitable dienes to afford hetero Diels-Alder cycloadducts in moderate yields

Synthesis and Structure–Activity Relationships of α‑Amino-γ-lactone Ketolides: A Novel Class of Macrolide Antibiotics

An efficient synthesis of α-amino-γ-lactone ketolide (<b>3</b>) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLS_B-resistant strains of <i>S. pneumoniae</i> and <i>S. pyogenes</i>. In addition, ketolide <b>11o</b> showed excellent <i>in vitro</i> antibacterial activity against <i>H. influenzae</i> strain as compared to telithromycin. These results indicate that C-21 substituted γ-lactone ketolides have potential as a next generation macrolide antibiotics