Allenic derivatives of nucleic acid components and their transformation products: a new class of biologically active nucleoside analogues.
Reaction of adenine (1a) or cytosine (1b) with excess 1,4-dichloro-2-butyne catalyzed by K2CO3 in (CH3)2SO gave the 4-chloro-2-butynyl derivatives 2a and 2b. The latter were converted to the 4-hydroxy-2-butynyl compounds 3a and 3b by refluxing in 0.1 M HCl. Isomerization of 3a in 0.1 M NaOH at 100 degrees C for 1 h gave an equilibrium mixture of 3a and allene 4a. Pure 4a was obtained by column chromatography. Similarly, compound 3b was transformed/0.1 M NaOH, 20% aq. dioxane, 9 h, 100 degrees C/ to a mixture of 3b and 4b from which pure 4b was obtained by chromatography and crystallization. By contrast, reflux of 3a or 3b in 1 M NaOH in 50% aq. dioxane for 1 h afforded cyclized products - dihydrofuryl derivatives 5a and 5b. Hydrogenation of 4a and 5a gave 9-(4-hydroxybutyl)adenine (6a) and 9-(tetrahydro-2-furyl)adenine (7a), respectively. Scope and limitations of allenic isomerization in nucleic acid base series, spectroscopy and biological activity of the obtained products will be discussed.
Phadtare
S
S
Department of Chemistry, Michigan Cancer Foundation, Detroit 48201.
Zemlicka
J
J
D000225:Adenine; D003596:Cytosine; D006843:Hydrocarbons, Chlorinated; D007202:Indicators and Reagents; D009705:Nucleosides / Q000138:chemical synthesis*
D006843:Hydrocarbons, Chlorinated; D007202:Indicators and Reagents; D009705:Nucleosides; C010709:1,4-dichloro-2-butene; D003596:Cytosine; D000225:Adenine