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

1‐(2′‐Deoxy‐β‐ D ‐ threo ‐pentofuranosyl)thymine (= 1‐(2′‐deoxy‐β‐ D ‐xylofuranosyl)thymine; xT d ; 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, xT d 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(T 12 ) ( 6 ; see Fig. 1 ), implying a left‐handed single strand. With d(A 12 ) ( 7 ) it could be hybridized to form a propably Left‐handed double strand d(A 12 ) · 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.