2′‐Deoxy‐β‐D‐ribofuranosides of N⁶‐Methylated 7‐Deazaadenine and 8‐Aza‐7‐deazaadenine: Solid‐phase synthesis of oligodeoxyribonucleotides and properties of self‐complementary duplexes

The syntheses of 7‐deaza‐ N 6 ‐methyladenine N 9 ‐(2′‐deoxy‐β‐ D ‐ribofuranoside) ( 2 ) as well as of 8‐aza‐7‐deaza‐ N 6 ‐methyladenine N 8 − and N 9 −(2′‐deoxyribofuranosides) ( 3 and 4 , resp.) are described. A 4,4′‐dimeth‐oxylritylation followed by phosphitylation yielded the methyl phosphoramidites 12–14 . They were employed together with the phosphoramidite of 2′‐deoxy‐ N 6 v‐methyladenosine ( 15 ) in automated solid‐phase oligonucleotide synthesis. Alternating or palindromic oligonucleotides derived from d(A‐T) 6 or d(A‐T‐G‐C‐A‐G‐A*‐T‐C‐T‐G‐C‐A) but containing one methylated pyrrolo[2,3‐ d ]pyrimidine or pyrazolo[3,4‐ d ]pyrimidine moiety in place of a N 6 ‐methylaminopurine (A*) were synthesized. Melting experiments showed that duplex destabilization induced by a N 6 ‐Me group of 2′‐deoxy‐ N 6 ‐methyladenosine is reversed by incorporation of 8‐aza‐7‐deaza‐2′‐deoxy‐ N 6 ‐meihyladenosine, whereas 7‐deaza‐2′‐deoxy‐ N 6 ‐methyladenostne decreased the T m value further. Regiospecific phosphodiester hydrolysis of d(A‐T‐G‐C‐A‐G‐m 6 A‐T‐C‐T‐G1‐C‐A) by the endodeoxyribonuclease Dpn I, yielding d(A‐T‐G‐C‐A‐G‐m 6 A) and d(pT‐C‐T‐G‐C‐A), was prevented when the residue c 7 m 6 A d ( 2 ), c 7 m 6 z 8 A d ( 3 ), or c 7 m 6 z 8 A d ′ ( 4 ) replaced m 6 A d ( 1 ) indicating that N(7) of N 6 ‐methyladenine is a proton‐acceptor site for the endodeoxyribonuclease.