Stereoselective synthesis of non symmetric dihydroxyethylene dipeptide isosteres via epoxy alcohols derived from alpha-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.
Benedetti
F
F
Dipartimento di Scienze Chimiche, Biofisica e Chimica delle Macromolecole, Università di Trieste, Italy. benedett@univ.trieste.it
Magnan
M
M
Miertus
S
S
Norbedo
S
S
Parat
D
D
Tossi
A
A
D000438:Alcohols / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D005030:Ethylenes / Q000138:chemical synthesis* / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry
D000438:Alcohols; D000596:Amino Acids; D019380:Anti-HIV Agents; D004151:Dipeptides; D004852:Epoxy Compounds; D005030:Ethylenes; D017320:HIV Protease Inhibitors; C067254:hydroxyethylene