Chemical and enzymatic synthesis of 4'-thio-beta-D-arabinofuranosylcytosine monophosphate and triphosphate.
N4-Acetyl-1-(2, 3-di-O-acetyl-4-thio-beta-D-arabinofuranosyl) cytosine (2) was synthesized in three steps from 1-(4-thio-beta-D-arabinofuranosyl) cytosine (1). The reaction of this partially blocked 4'-thio-ara-C derivative 2 with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one gave the 5-phosphitylate derivative 3, which on reaction with pyrophosphate gave the 5'-nucleosidylcyclotriphosphite 4. Product 4 was then oxidized with iodine/pyridine/water and deblocked with concentrated ammonium hydroxide to provide the desired 4'-thio-ara-C-5'-triphosphate 5. This triphosphate 5 was converted to 4'-thio-ara-C -5'-monophosphate 6 by treatment with snake venom phosphodiesterase I. The details of the synthesis, purification, and characterization of both nucleotides are described.
Fowler
A S
AS
Southern Research Institute, Birmingham, Alabama, USA.
Tiwari
K N
KN
Campbell
S R
SR
Secrist
J A
JA
D064753:Ammonium Hydroxide; D001085:Arabinofuranosylcytosine Triphosphate / Q000138:chemical synthesis* / Q000737:chemistry; D001088:Arabinonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002852:Chromatography, Ion Exchange; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives*; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D011756:Diphosphates / Q000737:chemistry; D015195:Drug Design; D006878:Hydroxides / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D043264:Phosphodiesterase I / Q000737:chemistry; D011122:Polyphosphates / Q000737:chemistry; D014867:Water / Q000737:chemistry
C506203:4'-thioarabinofuranosylcytosine monophosphate; D001088:Arabinonucleotides; D011756:Diphosphates; D006878:Hydroxides; D011122:Polyphosphates; D014867:Water; D001085:Arabinofuranosylcytosine Triphosphate; D064753:Ammonium Hydroxide; D003570:Cytidine Triphosphate; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom; D003568:Cytidine Monophosphate; C005692:triphosphoric acid