2,5-Anhydro-1-deoxy-1-phosphono-D-altritol, an isosteric analog of .alpha.-D-ribofuranose 1-phosphate

Abstract

Condensation of tetramethyl methylenebisphosphonate with 2,3-O-isopropylidene-5-O-trityl-D-ribose gave a mixture of 2,5-anhydro-1-deoxy-1-(diethoxyphosphinyl)-2,3 -O-isopropylidene-5-O-trityl-D-altritol and -allitol. Separation of the isomers and deprotection gave 2,5-anhydro-1-deoxy-1-phosphono-D-altritol and -allitol. The former is the stable isosteric methylenephosphonate analogue of alpha-D-ribose 1-phosphate, the ribose donor in nucleoside phosphorylase catalyzed nucleoside biosynthetic reactions. It did not, however, inhibit purine nucleoside phosphorylase at concentrations of 6 mM.

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

“…The routes start either from D-ribonic-γ-lactone ( 12 ) or D-ribose ( 13 ). For each route the key synthetic steps are the same involving installation of the dimethyl phosphonate moiety on a 2,3-O-isopropylidene ribofuranoside via a Wadsworth-Emmons reaction [4]. Route A (Scheme 2) started with acetonide protection of D-ribonic-γ-lactone ( 12 ) to generate 2,3-isopropylidene 14 [5].…”

“…In our case, even with limiting NaBH 4 , mixtures of diol 16 and 5-deoxy-5-fluoro-2,3-ribofuranoside 17 were obtained, however treatment with DIBAL-H at 40 °C [8] gave a clean reaction and 5-fluororibofuranoside 17 was recovered in moderate yield. Finally a Wadsworth-Emmons reaction [4] of 17 using tetramethyl methylenediphosphonate in DCM/aq. NaOH gave a smooth conversion to 5-fluorophosphonate 18 which had an α:β ratio of 3.2:1.…”

“…Following the protocol demonstrated by Meyer et al [4], 5- O -trityl-phosphonates 21a and 21b were obtained as individual epimers after chromatographic separation of the initial product mixture (α:β of 4:1). Detritylation of 21a , b was accomplished with ZnCl 2 [9] to generate the 5-hydroxyphosphonates 22a and 22b in a good yield.…”

Deoxy‐nitrosugars 12th communication Synthesis of isosteric mono‐phosphonate analogues of β‐and α‐D‐fructose 2,6‐bisphosphate

“…Deoxygenation of the imidazolylthiocarbonyloxy derivatives 10 with Bu,SnH in refluxing toluene [22] [23] gave the phosphonate 11 (79%). Signals of the CH,PO,Ph, group appeared in the 'H-NMR spectrum of 11 at 2.87 and 2.65 ppm (ABX, J(P,H) = 19.5 Hz, J,,,(H,H) = 15.4 Hz; CJ [24]) and in the "C-NMR spectrum at 29.05 ppm (dt, J(P,C) = 142.8 Hz; CJ [18] [25]). …”

“…The salt 2a was purified by flash chromatography on silylated silica gel. The structure of 2a was in agreement with the MS (FAB: M + 1 at 427), the 'H-NMR (3.67 and 3.61 ppm, AB, J = 12.3, CH20H; 1.95 ppm, d, J(P, H) = 18.5, CH,PO,Na,), the I3C-NMR (32.42 ppm, dt, J(P, C) = 128.5, CH,PO,Na,), and the 31P-NMR spectra (+20.19 ppm for C-PO,Na, and +2.10 ppm for 0-PO,Na,; cf: [I31 [18] [27] [28]). It was confirmed by elemental analysis.…”