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.
Department of Chemistry, Michigan Cancer Foundation, Detroit 48201.
S
S
Phadtare
J
J
Zemlicka
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