Antonella Migliorini

High-Yielding Synthesis of Methyl Orthoformate-Protected Hydroxytyrosol and Its Use in Preparation of Hydroxytyrosyl Acetate

The new methyl orthoformate of the powerful antioxidant hydroxytyrosol (or 2-(3,4-dihydroxyphenyl)ethanol) has been synthesized by a two-step high yielding procedure. The protection stabilizes hydroxytyrosol against fast oxidation and allows both easy chromatographic purification and long term storage. The protective group is hydrolyzed over pH = 10 and below pH = 5, thus allowing the release of the active principle under physiological conditions. The use of the methyl orthoformate-protected hydroxytyrosol allows the preparation of protected hydroxytyrosyl esters, like the acetate herein reported, by selective esterification of the alcoholic function. The subsequent quantitative deprotection under non-aqueous and mild conditions affords the hydroxytyrosyl acetate in high yields.

Synthesis of novel pyrrolyl-indomethacin derivatives

In the present work, we report the synthesis of the novel esters of indomethacin (IDMC) and an ester of reduced IDMC. For this purpose, IDMC is covalently bound by using a spacer chain to the pyrrole (Py) in the 3-position. The innovative pyrrole-indomethacin (3-Py-IDMC) derivates show no cytotoxic effects in primary calvarial osteoblasts. The designed IDMC derivates have been studied because they could be injected locally as a component of polymeric micro-particles. In fact, the new 3-Py-IDMC derivatives will assure their further polymerization since the 2- and 5-monomer positions are free.

Spiroaziridines from 4-Substituted alpha -ylidene-gamma-butyrolactones

4-Substituted a-ylidene-y-butyrolactones produce N-ethoxycarbonyl-spiroaziridino γ-lactone diastereomers on treatment with NsONHCO 2 Et and CaO. A good stereofacial preference is observed when the ring substituent is a phenyl group. These products are precursors of α-aminolactone as pure diastereomers.