Synthesis of the 3′-terminal half of yeast alanine transfer ribonucleic acid (tRNAAla) by the phosphotriester approach in solution. Part 1. Preparation of the nucleoside building blocks

Abstract

Adenosine and cytidine are converted into their 6-N- and 4-N-(4-t-butylbenzoyl) derivatives [(12) and (13b), respectively] which are then converted into the corresponding 2′-O-(4-methoxytetrahydropyran-4-yl)[(21; B =5b) and (21; B =6b), respectively] and 5′-O-[2-(dibromomethyl)benzoyl]2′-O-(4-methoxytetrahydropyran-4-yl) derivatives [(35; B =5b) and (35; B =6b), respectively]. The conversion of (12) into its 2′,3′-O-methoxymethylene derivative (24) is also described. Guanosine is converted, by two routes, into its 6-O-(3-chlorophenyl)-2-N-phenylacetyl derivative (16a), and the latter compound is converted into its 5′-O-[2-(dibromomethyl)benzoyl]-2′-O-(4-methoxytetrahydropyran-4-yl) and 5′-O-(9-phenylxanthen-9-yl)-2′-O-(4-methoxytetrahydropyran-4-yl) derivatives [(35; B =9b) and (26), respectively]. The preparation of 2′-O-(4-methoxytetrahydropyran-4-yl)-4-O-(2,4-dimethylphenyl)uridine (18) from 2′-O-(4-methoxytetrahydropyran-4-yl)uridine (17a) and its conversion to its 5′-O-[2-(dibromomethyl)benzoyl]derivative (35; B =10) are described. 5-Methyluridine (19; B =27), pseudouridine (19; B =28a) and inosine (19; B =29) are converted into their 2′-O-(4-methoxytetrahydropyran-4-yl) derivatives (21; B =27, 28a, and 29, respectively); (21; B =27) is further converted into its 4-O-phenyl derivative (30), (21; B =28a) is further converted into its 1-N-(4-bromobenzenesulphonyl) and 5′-O-[2-(dibromomethyl)benzoyl]-1-N-(4-bromobenzenesulphonyl) derivatives [(32) and (35; B =28b), respectively], and (21; B =29) is further converted into its 1-N-pivaloyloxymethyl- and 1-N-methyl derivatives [(33a) and (33b), respectively]. The N¹,N¹,N³,N³-tetramethylguanidinium E-2-nitrobenzaldoximate-promoted removal of O-aryl protecting groups from the 2′-O-(4-methoxytetrahydropyran-4-yl) derivatives of 6-O-(3-chlorophenyl)-2-N-phenylacetylguanosine, 4-O-(2,4-dimethylphenyl)uridine, 5-methyl-4-O-phenyluridine and 1-N-(4-bromobenzenesulphonyl)-5-β-D-ribofuranosyluracil [(21; B =9b), (18), (30), and (32), respectively], and the ammonia-promoted removal of the 1-N-pivaloyloxymethyl group from (33a) are described. Finally, the synthesis of 2-(isopropylthiomethoxymethyl)benzoic acid [Ptmt acid, (40)], the conversion of (18) and (21; B =5b) into their 5′-O-Ptmt derivatives [(41a) and (41b)], and the two-step procedure for the removal of the Ptmt protecting group are described.