Synthesis and sulfation of an acetamido group-containing copolyribose was carried out by a five-step synthetic route. Firstly, selective ring-opening copolymerization of 1, 4-anhydro-3-azido-2-
O-
t-butyldimethylsilyl (TBDMS)-3-deoxy-α-D-ribopyranose (A3ASR) and 1, 4-anhydro-2, 3-di-
O-TBDMS-α-D-ribopyranose (ADSR) with BF
3•OEt
2 as a catalyst at low temperature produced an azido group-containing copolyribose, i.e., poly [ 3-azido-2-
O-TBDMS-3-deoxy-(1→5)-α-ribofuranose-co-2, 3-di-
O-TBDMS-(1→5)-α-ribofuranose] [copoly (A3ASR)]. The number-average molecular weight (_??_
n) of the azido group-containing copolyriboses was in a range of 1.17×10
4 to 2.96×10
4. The specific rotation ([α]
20D) increased from +117° to +204° as the mole fractions (%) of azido group-containing units (A3ASR) in the copolymers decreased from 83% to 16%. The reactivity ratios of A3ASR (r
1=0.42) and ADSR (r
2=1.16) in the ring-opening copolymerizations were estimated according to the Kelen-Tudos method.
Then, the azido group in a copoly (3A3ASR-ADSR) (_??_
n of 1.11×10
4 and [α]
20D of +141.6°) was reduced into amino group with NaBH4 in a mixture of THF-ethanol to afford an amino group-containing copolymer, i.e., poly [3-amino-2-
O-TBDMS-3-deoxy-(1→5)-α-ribofuranose-co-2, 3-di-
O-TBDMS-(1→5)-α-ribofuranose] [copoly (AAmSR-ADSR)], and subsequent acetylation of the amino group with acetyl chloride gave an intermediate acetamido group-containing copolymer, i.e., poly [ 3-acetamido-2-
O-TBDMS-3-deoxy-(1→5)-α-ribofuranose-co-2, 3-di-
O-TBDMS-(1→5)-α-ribofuranose] [copoly (A3AAdSR-ADSR)], and then de-
t-butyldimethylsilylation of the copolymer produced a water-soluble acetamido group-containing copolyribose, i.e., poly [ 3-acetamido-3-deoxy-(1→5)-α-ribofuranose-co-(1→5)-α-ribofuranose] [copoly (A3AAdR-R)] with _??_
n of 8.63×10
3 and [α]
20D of +141.0°.
Finally, sulfation of the acetamido group-containing copolyribose [copoly (A3AAdR-R)] with a sulfur trioxide-pyridine complex in a mixture of dimethyl sulfoxide (DMSO) and pyridine produced a sulfated acetamido group-containing copolyribose [copoly (SA3AAdR-SR)] with _??_
n of 10.68×10
3 and [α]
20D of + 84.9°. The structures of acetamido group-containing copolymer and its sulfate were determined by
13C NMR. The degree of sulfation (DS=1.2) was measured by elemental analysis.
View full abstract