1‐(2′‐Deoxy‐β‐ D ‐xylofuranosyl)thymine Building Blocks for Solid‐Phase Synthesis and Properties of Oligo(2′‐Deoxyxylonucleotides)

Abstract 1‐(2′‐Deoxy‐β‐D‐threo‐pentofuranosyl)thymine (= 1‐(2′‐deoxy‐β‐D‐xylofuranosyl)thymine; xTd; 2) was converted into its phosphonate 3b as well as its 2‐cyanoethyl phosphoramidite 3c. Both compounds were used for solid‐phase synthesis of d[(xT)12‐T] (5), representing the first DNA fragment build up from 3′–5′‐linked 2′‐deoxy‐‐β‐D‐xylonucleosides. Moreover, xTd was introduced into the innermost part of the self‐complementary dodecamer d(G‐T‐A‐G‐A‐A‐xT‐xT‐C‐T‐A‐C)2 (9). The CD spectrum of d[(xT)12–T] (5) exhibits reversed Cotton effects compared to d(T12) (6; see Fig. 1), implying a left‐handed single strand. With d(A12) (7) it could be hybridized to form a propably Left‐handed double strand d(A12) · d[(xT)12–T] (7·5) which was confirmed by melting experiments in combination with temperature‐dependent CD spectroscopy. While 5 was hydrolyzed by snake‐venom phosphodiesterase, it was resistant towards calf‐spleen phosphodiesterase. The modified, self‐complementary duplex 9 was hydrolyzed completely by snake‐venom phosphodiesterase, at a twelvefold slower rate compared to unmodified 8; calf‐spleen phosphodiesterase hydrolyzed 9 only partially.