Synthesis of Optically Active 1,4-Dioxane Nucleotide Analogs

Abstract

Optically active nucleotide analogs were prepared that were composed of a 1,4-dioxane ring as the sugar analog to which either uracil or adenine attached together with two carboxylic ester groups, to be used as vehicles for formation of oligomers. The chiral 1,4-dioxane moiety was constructed from dimethyl L-tartrate via the corresponding (2R,3R)-dimethyl 2-O-allyl-tartrate.

Enantioselective Synthesis of Homo-N-Nucleosides Containing a 1,4-Dioxane Sugar Analog

“…The formation of the 1,4-dioxane homo-sugar analog 4 was readily achieved starting from (2 R ,3 R )-dimethyl tartrate, an inexpensive and commercial available chiral starting material. Thus, (2 R ,3 R )-dimethyl tartrate was converted into the corresponding enantiomerically pure allyl ether 1 [ 9 ] either by the reaction with allyl bromide in the presence of silver oxide [ 10 ] or in a tin assisted reaction with dibutyltin oxide [ 11 , 12 ]. The dimethyl (2 R ,3 R )-2- O -allyltartrate 1 was then reduced by LiAlH 4 [ 13 , 14 , 15 ] or NaBH 4 [ 16 , 17 ] to give triol 2 .…”

“…The solvents were purified by standard methods. The preparations of compounds 1 were described elsewhere [ 9 , 10 , 11 , 12 ].…”