Ethyl Corporation

John N Freskos

K Pushpananda Senaratne

An O-, S-, or N-silyl- or O-, S-, or N-alkylpyrimidine is reacted with a protected 1-halo-, 1-alkoxy-, or 1-acyloxy-2-deoxy sugar in the presence of cuprous iodide and a halohydrocarbon solvent to prepare a nucleoside having an improved beta-anomer/alpha-anomer ratio. In a preferred embodiment of the invention, 2,4-bis(trimethylsilyloxy)-5-methylpyrimidine or 2,4-bis(trimethylsilyloxy)-5-ethylpyrimidine is reacted with 2-deoxy-3,5-di-O-p-toluyl-D-erythro-ribofuranosyl chloride in the presence of cuprous iodide and chloroform.

Process for preparing 2-deoxynucleosides

A process is provided in which a mixture of alpha- and beta-anomers is converted selectively to the desired beta-thymidine. The process involves the following steps: (a) converting a mixture of alpha- and beta-anomers of tetra-O-acylribofuranose to tri-O-acyl-.beta.-ribothymidine; (b) converting tri-O-acyl-.beta.-ribothymidine to .beta.-ribothymidine; (c) converting .beta.-ribothymidine to 2,2'-anhydro-.beta.-thymidine; (d) converting 2,2'-anhydro-.beta.-thymidine to 2'-halo-2'-deoxy-5-methyluridine; and (e) converting 2'-halo-2'-deoxy-5-methyluridine to beta-thymidine. The mixture of alpha- and beta-anomers of tetra-O-acylribofuranose may be produced by any suitable procedure such as by converting lower alkyl ribofuranoside to the tetra-O-acylribofuranose mixture. The lower alkyl ribofuranosides may in turn be produced by various methods. However, a desirable way of effecting this conversion involves use of D-ribose as the starting material which is converted to the lower alkyl ribofuranoside.

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Baton Rouge, LA, United States of America

John N Freskos