Novel cost-effective methanephosphonoanilidothioate approach to the stereoselective synthesis of dinucleoside (3',5')-methanephosphonates.
A new method of stereoselective preparation of di(2'-deoxy or 2'-OMe)ribonucleoside (3',5')-methanephosphonate 5 is presented. The DBU/LiCl-assisted reaction of 5'-O-DMT-(2'-deoxy or 2'-OMe)ribonucleoside 3'-O-(S-alkyl methanephosphonothioate) 9 with 5'-OH nucleosides proceeds with full stereospecificity, giving 5 in moderate to good yield. The conversion of 5'-O-DMT-(2'-deoxy or 2'-OMe) ribonucleoside 3'-methanephosphonoanilidothioates 8 and 3'-O-methanephosphonoanilidates 10 by means of NaH/CX2 (X = O,S) followed by S-alkylation leads to monomers 9, with the possibility of use of both separated diastereomers of 8 for the preparation of one selected diastereomer of 5. The relative configuration at the P atom in 2'-OMe and deoxynucleoside derivatives of compounds 9 was established by means of stereoselective degradation of nucleoside 3'-O-methanephosphonothioates 11 (precursors of 9) with nuclease P1.
Stec
W J
WJ
Department of Bioorganic Chemistry, Polish Academy of Sciences, Lódź, Poland.
Woźniak
L A
LA
Pyzowski
J
J
Niewiarowski
W
W
D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013873:Thionucleotides
D007202:Indicators and Reagents; D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; D013873:Thionucleotides