Stefano Norbedo

Regio- and stereoselective ring opening of 2,3-epoxyalcohols with diethylaluminium azide

Abstract 2,3-Epoxyalcohols react with diethylaluminium azide under mild conditions to give 3-azido-1,2-diols resulting from the regio- and stereoselective attack of the nucleophile at the epoxide C-3. The high regioselectivity (>25:1) observed with both cis and trans substituted epoxides is not affected by bulky substituents at C-3. The method has been successfully applied also to the synthesis of diaminodiol dipeptide isosteres.

Facile inversion of configuration of N-Boc-β-aminoalcohols via SN2 cyclization to oxazolidinones

Abstract Oxazolidinones are obtained by the cyclization of mesylates derived from N-Boc-β-aminoalcohols. Hydrolysis of the N-Boc-oxazolidinones regenerates the protected aminoalcohols with inverted configuration at the hydroxy group.

Ring-opening of epoxyalcohols by diethylaluminium cyanide. Regio- and stereoselective synthesis of 1-cyano-2,3-diols

Abstract Diethylaluminium cyanide is a highly selective reagent for the ring opening of 2,3-epoxyalcohols under mild conditions; the reaction takes place at C-3, with inversion of configuration, to give 1-cyano-2,3-diols.

Stereoselective synthesis of non symmetric dihydroxyethylene dipeptide isosteres via epoxyalcohols derived from α-amino acids

(1R,2R,3S,4S)-4-Amino-3-hydroxy-1,2-epoxybutanes, accessible in four steps from L-aminoesters, react regio- and stereoselectively with diethyl aluminum cyanide to give (1R,2S,3S,4S)-4-amino-2,3-dihydroxynitriles. Hydrolysis yields hydroxylactones equivalent to 2,3-dihydroxy-4-aminoacids. The sequence provides a novel approach to dihydroxyethylene isosteres potentially useful for new HIV-protease inhibitors.

New synthesis of 5-amino-4-hydroxy-2,6-dimethylheptanoic acid, a hydroxyethylene isostere of the Val-Ala dipeptide

Abstract Two stereoisomers of the title compound have been synthesized from the methyl ester of N -Boc L-valine. The aminoester was initially converted into an α′-amino α,β-unsaturated ketone via a phosphonoketone and a Horner–Emmons olefination with acetaldehyde. Hydrocyanation of the enone with diethylaluminium cyanide and functional group conversions gave the hydroxyaminoacids protected as oxazolidines or as lactones.

Epoxyalcohol route to hydroxyethylene dipeptide isosteres: a new synthesis of the diaminoalcohol core of HIV-protease inhibitor ABT-538 (Ritonavir)

A stereoselective synthesis of the diaminoalcohol core of Ritonavir illustrates a novel approach to hydroxyethylene dipeptide isosteres, based on the regioselective reduction of amino acid-derived epoxyalcohols.