TY - JOUR
T1 - Efficient synthesis of methylenebis(phosphonate) analogues of P1,P2-disubstituted pyrophosphates of biological interest. A novel plausible mechanism
AU - Pankiewicz, Krzysztof W.
AU - Lesiak, Krystyna
AU - Watanabe, Kyoichi A.
PY - 1997/4/23
Y1 - 1997/4/23
N2 - Synthesis of novel nucleoside bicyclic trisanhydrides 7 in the reaction of nucleoside-5'-methylenebis(phosphonate)s (4) with DCC is described. They were obtained by P1,P3- and P2,P4-dehydration of initially formed P1,P2,P3,P4-bismethylenetetraphosphonate 6. Reaction of 7 (N = 2',3'-O-isopropylideneadenosin-5'-yl) with 2',3'O-isopropylidenetiazofurin gave, after hydrolysis and deisopropylidenation, β-methylene-TAD (10a), the known potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). Similar reaction of 7 with benzyl 2,3-O-isopropylidene-β-D-riboside followed by hydrolysis and deprotection afforded a new methylenebis(phosphonate) analogue of ADP-ribose 10b. Upon reaction of 7 with riboflavin, the corresponding β-methylene-FAD (10c) was obtained. Bicyclic trisanhydride 7 prepared from (2',3'-O-isopropylidene-N4-acetylcytidin-5'-yl)methylenebis(phosphona te) was used in the synthesis of the methylenebis(phosphonate) analogues of CDP-ethanolamine 10d and CDP-dipalmitoylglycerol 10e.
AB - Synthesis of novel nucleoside bicyclic trisanhydrides 7 in the reaction of nucleoside-5'-methylenebis(phosphonate)s (4) with DCC is described. They were obtained by P1,P3- and P2,P4-dehydration of initially formed P1,P2,P3,P4-bismethylenetetraphosphonate 6. Reaction of 7 (N = 2',3'-O-isopropylideneadenosin-5'-yl) with 2',3'O-isopropylidenetiazofurin gave, after hydrolysis and deisopropylidenation, β-methylene-TAD (10a), the known potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). Similar reaction of 7 with benzyl 2,3-O-isopropylidene-β-D-riboside followed by hydrolysis and deprotection afforded a new methylenebis(phosphonate) analogue of ADP-ribose 10b. Upon reaction of 7 with riboflavin, the corresponding β-methylene-FAD (10c) was obtained. Bicyclic trisanhydride 7 prepared from (2',3'-O-isopropylidene-N4-acetylcytidin-5'-yl)methylenebis(phosphona te) was used in the synthesis of the methylenebis(phosphonate) analogues of CDP-ethanolamine 10d and CDP-dipalmitoylglycerol 10e.
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U2 - 10.1021/ja964058i
DO - 10.1021/ja964058i
M3 - Article
AN - SCOPUS:0030997672
SN - 0002-7863
VL - 119
SP - 3691
EP - 3695
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 16
ER -