Synthesis of 2'(3')-O-Aminoacyl Triribonucleoside Diphosphates Using the Triester Method

Article abstract of DOI:10.1021/jo00343a007

Specific syntheses of 2'(3')-O-aminoacyl triribonucleoside diphosphates, C-C-A-Phe (16e), C-C-A-Ala (16f), and C-C-A-Gly (16g), which are the terminal sequences of corresponding aa-tRNAs and potential substrates for ribosomal peptidyltransferase, are described.The compounds 16e-g were synthesized by employing phosphotriester methods with a benzoyl group for protection of heterocyclic amino groups, a 2-chlorophenyl group for internucleotide phosphate protection, a monomethoxytrityl group for blocking of the 5'-hydroxy function, a 4-methoxytetrahydropyranyl group forprotection of 2'-hydroxy functions, and an N-benzyloxycarbonyl group for blocking of the α-amino acid.Protected dinucleotide block C-Cp (11b) was synthesized via the triester method and was condensed by using mesitylenesulfonyl tetrazolide with nucleoside components 9b and 10b, which have aminoacyl residues incorporated in the molecule, to yield protected aminoacyl trinucleotides 13a and 14 in 60-70percent yields.The fully protected aminoacyl trinucleotides 13a and 13b were also obtained from the protected C-C-A derivative 12 (with a free 3'-OH group on the 3'-terminus) by the aminoacylation reaction with corresponding N-benzyloxycarbonyl amino acids and mesitylenesulfonyl tetrazolide in 50-70percent yields.The protected derivatives 13a,b and 14 were deblocked to form C-C-A(Z-Phe) (16b), C-C-A(Z-Ala) (16c), and C-C-A(Z-Gly) (16d) in 15-40percent yields by reactions with N2H4, F-, and H+ (for 16b,c) or NH4OH and H+ (for 16d).The final products 16e-g were prepared by hydrogenolysis (Pd/BaSO4) of 16b-d in practically quantitative yields.The syntheses of all components (3a,c,4,9a,b, and 10b) for the triester approach to aminoacyl trinucleotides are also described.