Nucleic Acid Derived Allenols: Unusual Analogues of Nucleosides with Antiretroviral Activity

Article abstract of DOI:10.1021/ja00197a063

Racemic 1,2-butadien-4-ols substituted with a nucleic acid base were prepared by a base-catalyzed isomerization of the corresponding 2-butynols.With basic heterocycles such as adenine, cytosine, 5-methylcytosine, or N-<(dimethylamino)methylene>guanine, the respective allenes were obtained without difficulty, but with guanine, side reactions were observed.Reaction of 2-butynols in stronger base (1 M NaOH) gave cyclized products-oxacyclopentenes 8a-c. (+/-)-Adenallene (3a) and (+/-)-cytallene (3c) are strong inhibitors of replication of human immunodeficiency virus(HIV) in vitro. (+/-)-Adenallene (3a) and butyne 6a are substrates for adenosine deaminase.Racemic 3a was deaminated quantitatively to (+/-)-hypoxallene (3h), indicating a low stereoselectivity as contrasted with the natural substrate-adenosine.When the deamination was stopped ad ca. 50percent conversion, (-)-adenallene (3a) and (+)-hypoxallene (3h) were obtained.Antiretroviral and adenosine deaminase substrate activities are discussed in terms of the similarity of several steric and stereoelectronic features of allenic derivatives of nucleic bases with those of the corresponding nucleosides or 2',3'-dideoxyribonuclesides.