The synthesis of oligoribonucleotides. III. The use of silyl protecting groups in nucleoside and nucleotide chemistry. VIII

Abstract

The synthesis of all isomeric mono- and disilyl derivatives of cytidine, guanosine, and their N-benzoyl analogues using the tert-butyldimethylsilyl protecting group is described. These compounds and those containing a 5′-monomethoxytrityl group have been condensed via the phosphodichloridite procedure to produce nucleotides rapidly and in good yields. The synthesis of 2′–5′-linked nucleotides is described. A cautionary note is introduced in regard to the preparation of 5′-monomethoxytritylguanosine and a novel methanolysis of certain N-benzoylcytidines is mentioned.

Modified phosphotriester method for chemical synthesis of ribooligonucleotides. Part I. Synthesis of riboundecaadenylate and two fragments constituting the sequence of R-17 translation control signal

“…log (17%). The structure of the 2'-protected isomer was confirmed by comparison with literature values (13).…”

“…described in ref. 13. Purification by silica gel (160g) chromatography and subsequent isomerization of the 3'-silylated isomer and repeated chromatography (three times) as described above yielded the pure 2'-tert-butyldimethyl silyl isomer, 31g (50%) and the 3'-isomer, 9 g (15%).…”

“…The first dimension is electrophoresis on cellulose acetate strip of pH 3.5 and the second dimension is homochromatography on 20 cm x 20 cm DEAE-cellulose plate in solvent Homo-V. silylated derivative (16g) was treated with triethylamine (0.5 structure of the 2'-protected isomer was confirmed by comparmL) in methanol (200 mL) for 40 min at room temperature. On ing its nmr spectral data with the literature values (13). removing the solvent in cacuo, a gum was produced which was again chromatographed on a silica gel column as described 5'-Dimethoxytrityl2'-tert-butyldimethyl silyl uridine above to yield a further 9 g of the 2'-protected isomer.…”

“…Finally deprotection must occur under conditions which prevent any 3' to 2' migration of the internucleotidic phosphodiester linkages. The most commonly utilized 2'-hydroxyl protecting groups are substituted tetrahydropyran (9) and 0-nitrobenzyl (l2), but their introduction requires multiple chemical steps, whereas tertbutyldimethyl silyl (TBDMS), a bulkier protecting group, has been employed by Ogilvie et a1 (13). The main advantages of this protecting group are its ease of protecting the 2'-hydroxyl function and also stability towards acidic and basic conditions in order to avoid migration and cleavage of 3' 4 5' phosphodiester linkages.…”

The synthesis of oligoribonucleotides VI. The synthesis of a hexadecamer by a block condensation approach

“…We have previously described in detail the synthesis of all levels of silylated ribonucleosides and the general procedures for the synthesis of nucleotides up to the tetranucleotide stage (2,3,5). We 'This article also constitutes Part XI in a series on silyl protecting groups in nucleoside and nucleotide chemistry.…”