1. Enantiomerically pure phosphonated carbocyclic 2'-oxa-3'-azanucleosides: synthesis and biological evaluation
- Author
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Romeo, Roberto, Carnovale, Caterina, Giofre, Salvatore, V., Monciino, Giulia, Chiacchio, MARIA ASSUNTA ROSSELLA, Sanfilippo, Claudia, and Macchi, Beatrice
- Subjects
PCOANs ,Stereochemistry ,antiretroviral ,Organophosphonates ,Pharmaceutical Science ,Stereoisomerism ,HIV Infections ,N ,O-modified nucleosides ,Antiretrovirals ,Article ,Analytical Chemistry ,O-modified nucleoside ,lcsh:QD241-441 ,chemistry.chemical_compound ,Structure-Activity Relationship ,lcsh:Organic chemistry ,Drug Discovery ,Structure–activity relationship ,Molecule ,Humans ,Hydroxymethyl ,Physical and Theoretical Chemistry ,N,O-modified nucleosides ,Molecular Structure ,Organic Chemistry ,Settore BIO/14 ,HIV ,Phosphonates ,Nucleosides ,Settore CHIM/06 - Chimica Organica ,U937 Cells ,Phosphonate ,In vitro ,chemistry ,Chemistry (miscellaneous) ,Molecular Medicine ,Enantiomer - Abstract
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.
- Published
- 2014