Synthesis of a Novel Aldehyde: 4-O-Methyl-5-formylmethyl- 2′-deoxyuridine

Abstract

The synthesis of the blocked nucleoside 3′,5′-di-O-p-toluoyl-4-O-methyl-5-formylmethyl-2′-deoxyuridine (19) was accomplishied in eleven steps from gamma-butyrolactone. This aldehyde, which should facilitate the synthesis of nucleosides containing ¹⁸F, was converted to the corresponding blocked dithianyl nucleoside (21), and also to 5-(2,2-difluoroethyl)-substituted derivatives of 2′-deoxyuridine and 2′-deoxycytidine.

Key Words:

• Gem-difluoro
• Deoxyuridine
• Aldehyde
• Reductive tritualation
• Dithioacetals

Acknowledgments

We thank German Academic Exchange Service (DAAD) and DKFZ for the financial support. We thank Prof. Chun-Hung Lin (Institute of Biological Chemistry, Academia Sinica, Taiwan) for his reviewing this manuscript.

Notes

Protons H-9, H-10 and H-11 were identified by two-dimensional ¹H-NMR (COSY).

The signal of C-5 was very broad due to coupling with the two F'S. The signal of C-2 was broad.