223. Phosphoramidites of Chiral (RP)- and (SP)-Configurated d(T-A): Synthesis, Configurational Assignment, and Use as Dimer Blocks in Oligonucleotide Synthesis

Article abstract of DOI:10.1002/hlca.19850680805

The N,N-diisopropylphosphoramidites 10a and 10b of appropriately protected chiral diastereoisomers of d(T>P-18O>-A) (8a and 8b, resp.), chiral by virtue of the isotope 18O at the P-atom, have been synthesized.The 18O-isotope was incorporated by oxidation of the phosphite triester 3 with H2<18O>/I2.Separation of the diastereoisomers was accomplished by flash chromatography of the O-3'-deprotected phosphate triesters 5a/b.The absolute configuration at the chiral P-atom was deduced from the methylation products of the fully deprotected diastereoisomers 8a and 8b.Phosphinylation of 5a and 5b yielded the configurationally pure phosphoramidites 10a and 10b, respectively, which were then employed in solid-phase synthesis to yield the self-complementary oligomers d(G-A-G-T-(R_P)--A-C-T-C) (13) and d(G-A-G-T-(S_P)--A-C-T-C) (14), respectively.