Articolo in rivista, 2014, ENG, 10.3390/molecules190914406

Enantiomerically Pure Phosphonated Carbocyclic 2'-Oxa-3'-Azanucleosides: Synthesis and Biological Evaluation

Roberto Romeo , Caterina Carnovale , Salvatore V. Giofrè , Giulia Monciino , Maria A. Chiacchio , Claudia Sanfilippo, Beatrice Macchi

Dipartimento Scienze del Farmaco e Prodotti per la Salute, Università di Messina, Via S.S. Annunziata, 98168 Messina, Italy; Dipartimento Scienze del Farmaco, Università di Catania, Viale A. Doria 6, 95125 Catania, Italy; Istituto di Chimica Biomolecolare del CNR, Via P. Gaifami 18, 95126 Catania, Italy; Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", 00133 Roma, Italy;

Starting from enantiomeric pure 1-[(3S,5R)- and 1-[(3R,5S)-3-(hydroxymethyl)- 2-methylisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-diones (-)7a and (+)7b, obtained by lipase-catalyzed resolution, pure diethyl{[(3S,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4- dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (-)12a and diethyl{[(3R,5S)- 2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl} phosphonate (+)12b have been synthesized. The obtained compounds showed no cytotoxic activity versus the U937 cell line in comparison with AZT, and were poorly able to inhibit HIV infection in vitro.

Molecules (Basel, Online) 19 , pp. 14406–14416

Keywords

PCOANs, N, O-modified nucleoside, antiretroviral

CNR authors

Sanfilippo Claudia

CNR institutes

ICB – Istituto di chimica biomolecolare